NTA Level 5 • Semester 2 • PST05208

Pharmaceutics Theory and Compounding – Complete Full Notes

Complete educational source text in one page

Completeness safeguard: this page keeps the complete educational module/source wording in one place so learning material is not lost when browsing topic by topic. Presenter/tutor metadata is intentionally excluded.

UNITED REPUBLIC OF TANZANIA

Ministry of Health, Community

Development, Gender, Elderly and

Children

PST 05208

Pharmaceutics Theory

and Compounding

NTA Level 5 Semester 2

Facilitator Guide

March 2019

PST 05208 Pharmaceutics Theory & Compounding NTA Level 5 Semester 2 Facilitator Guide

Table of Contents

Background …………………………………………………………………………………………………………………… iv

Abbreviations/Acronym …………………………………………………………………………………………………. xii

Session 1: Introduction to Sterile Pharmaceutical Preparations …………………………………………….. 1

Session 2: Aseptic Processing…………………………………………………………………………………………… 8

Session 3: Requirements for Preparation of Sterile Pharmaceutical Products ……………………….. 13

Session 4: Percutaneous Absorption ………………………………………………………………………………… 19

Session 5: Semi Solid Preparations………………………………………………………………………………….. 27

Session 6: Reference and Formula in Pharmaceutical production………………………………………… 34

Session 7: Compounding of Ointments ……………………………………………………………………………. 47

Session 8 Compounding of Pastes …………………………………………………………………………………… 57

Session 10: Compounding of Gels/ Jellies………………………………………………………………………… 74

Session 11: Introduction to Isotonicity …………………………………………………………………………….. 84

Session 12: Determination of Isotonicity by Freezing Point Method ……………………………………. 92

Session 13: Determination of Isotonicity by Sodium Chloride Equivalent Method ……………….. 98

Session 14: Determination of Isotonicity by Molecular Concentration Method …………………… 104

Session 15: Calculations Involving Milliequivalent …………………………………………………………. 108

Session 16: Calculations Involving Millimoles ……………………………………………………………….. 115

Session 17: Calculations Involving Milliosmoles (mOsmol) …………………………………………….. 120

Session 18: Calculations Involving Osmolarity……………………………………………………………….. 125

Session 19: Calculations Involving Constituted Solutions ………………………………………………… 131

Session 20: Calculations Involving Intravenous Admixture ……………………………………………… 140

Session 21: Calculations Involving Rate of Flow of Intravenous Fluid ………………………………. 145

Session 22: Calculations Involving Buffer Solutions ……………………………………………………….. 150

Session 23: Preservation of Pharmaceutical Product ………………………………………………………… 157

PST 05208 Pharmaceutics Theory & Compounding NTA Level 5 Semester 2 Facilitator Guide

iii

Background

There is currently an ever-increasing demand for pharmaceutical personnel in Tanzania.

This is due to expanding investment in public and private pharmaceutical sector. Shortage of

trained pharmaceutical human resource contributes to poor quality of pharmaceutical

services and low access to medicines in the country (GIZ, 2012).

Through Public-Private-Partnership (PPP) the Pharmacy Council (PC) together with

Development Partners (DPs) in Germany and Pharmaceutical Training Institutions (PTIs)

worked together to address the shortage of human resource for pharmacy by designing a

project named “Supporting Training Institutions for Improved Pharmaceutical Services in

Tanzania” in order to improve quality and capacity of PTIs in training.

CSSC prepared a Multi-actor Partnership (MAP) project proposal on how to sustain and

strengthen health care in Tanzania through improvement of pharmaceutical training and an

inter-institutional coordination of actors. This will harmonize and improve access to quality

pharmaceutical service in Tanzania.

The project has a various key stakeholders like; CSSC, NACTE, PC, TCU, CEDHA and

Pharmaceutical Training Institutions (PTIs). Through this project, few PTIs will receive

infrastructural improvements to increase the quantitative and qualitative capacities (CUHAS,

RUCU and KSP). Furthermore this project will train Pharmaceutical tutors from different

PTIs on teaching and assessment methods in Tanzania and thus improved health delivery

through increased qualified human resource.

It was also observed that in the previous stakeholder‟s meetings there was a need for the

development of training manuals and assessment plans for NTA Level 5 & 6, in order to

support the establishment and implementation of the curriculum in PTIs. During MAP kick-

off workshop done in February 2018, Stakeholders agreed that there was a need for

development of the said manuals and it was among the highest priority in Pharmacy

education in Tanzania. Therefore this project aims at developing facilitator‟s guide and

assessment plans for NTA Level 5 & 6.

Pharmacy Council, CSSC and action medeor developed the Terms of Reference and selected

a qualified service provider with experience in material development to develop the

mentioned training manuals and assessment plan. Centre for Educational Development in

Health Arusha (CEDHA) was selected and offered a contract to develop Facilitators guide for

NTA level 5 & 6 and assessment plan.

Centre for Educational Development in Health Arusha (CEDHA) was offered a leading role

with the instructions to include experts who have developed teaching materials for NTA

Level 4. These experts are primarily experienced pharmaceutical and non-pharmaceutical

tutors.

The mode of operation used by CEDHA to develop facilitators guide and assessment plan

was participatory approach which included a number of activities through various workshops

PST 05208 Pharmaceutics Theory & Compounding NTA Level 5 Semester 2 Facilitator Guide

such as planning, and orientation of material development. After these preliminary

workshops, experts developed materials individually and in-groups. Thereafter, developed

draft materials were reviewed, edited and formatted and draft one was finalized and shared to

stakeholders for inputs.

Finally, CEDHA submitted the finalized Facilitator‟s guides and assessment plans for NTA

level 5 and 6 to CSSC for endorsement, printing, dissemination and sharing with relevant

authorities.

There are 11 modules for NTA level 5 making 11 facilitator guides including one practicum

guide.

PST 05208 Pharmaceutics Theory & Compounding NTA Level 5 Semester 2 Facilitator Guide

Acknowledgment

The development of standardized training materials of a competence-based curriculum for

pharmaceutical sciences has been accomplished through involvement of different

stakeholders.

Special thanks go to the Pharmacy Council for spearheading the harmonization of training

materials in the pharmacy after noticing that training institutions in Tanzania were using

different curricula and train their students differently.

I would also like to extend my gratitude to Christian Social Service Commission (CSSC) for

their tireless efforts to mobilize funds from development partners (German Ministry of Industry

and action medeor). It is through the implementation of the Multi-Actors Partnership (MAP)

project, CSSC has been able to provide the financial and technical support needed during the

development of this training material.

Many thanks go to the Centre for Educational Development in Health Arusha (CEDHA)

experts on health material development and training who coordinated the development of

these module sessions particularly Ms. Diana H. Gamuya for her commitment in coordinating

and facilitating the planning and development to its completion.

Particular acknowledgements are sent to Mr. Dickson Mtalitinya and Members from the

secretariat of National Council for Technical Education (NACTE) for facilitating and

providing their expertise to the success of this work.

It will be unfair if I will not recognize the efforts and contributions of all CEDHA supportive

staff that made this process a success; accountant, secretary, drivers and printers

Finally, I very much appreciate the contributions of the tutors and content experts

representing PTIs, hospitals, and other health training institutions. Their participation in

meetings and workshops, and their input in the development of this training

manual/facilitators guide have been invaluable.

These participants are listed with our gratitude below:

Ms. Elizabeth Shekalaghe Registrar, Pharmacy Council of Tanzania

Dr. Fadhili Lyimo Assistant Director Allied Health,MoHCDGEC

Dr. Catherine Jincen Acting Principal, CEDHA

Dr. Sungwa N. Kabissi Project Manager – MAP, CSSC

Ms. Diana H. Gamuya CEDHA

Ms. Grace Mallange PC

Ms. Emily Mwakibolwa Pharmacy Council

PST 05208 Pharmaceutics Theory & Compounding NTA Level 5 Semester 2 Facilitator Guide

vii

Ms. Tumaini H. Lyombe MUHAS

Ms. Dilisi J. Makawia KSP

Director of Human Resources Development

Ministry of Health, Community Development, Gender, Elderly and Children

PST 05208 Pharmaceutics Theory & Compounding NTA Level 5 Semester 2 Facilitator Guide

viii

Introduction

Module Overview

This module content is a guide for tutors of Pharmaceutical schools for training of students.

The session contents are based on sub-enabling outcomes and their related tasks of the

curriculum for Technician Course in Pharmaceutical Sciences. The module sub-enabling

outcomes and their related tasks are as indicated in the in the Technician Certificate in

Pharmaceutical Sciences (NTA Level 5) Curriculum

Target Audience

This module is intended for use primarily by tutors of pharmaceutical schools. The module‟s

sessions give guidance on the time, activities and provide information on how to teach the

session. The sessions include different activities, which focus on increasing students‟

knowledge, skills and attitudes.

Organization of the Module

The module consists of twenty three (23) sessions; each session is divided into several parts

as indicated below:

• Session Title: The name of the session

• Total Session Time: The estimated time for teaching the session, indicated in minutes

• Pre-requisites: A module or session, which needs to be covered before teaching the

session.

• Learning Tasks: Statements which indicate what the student is expected to learn by the

end of the session

• Resources Needed: All resources needed for the session are listed including handouts

and worksheets

• Session Overview: The session overview box lists the steps, time for each step, the

activity or method used in each step and the step title

• Session Content: All the session contents are divided into steps. Each step has a heading

and an estimated time to teach that step as shown in the overview box. Also, this section

includes instructions for the tutor and activities with their instructions to be done during

teaching of the contents

• Key Points: Key messages for concluding the session contents at the end of a session

This step summarizes the main points and ideas from the session, based on the learning

tasks of the session

• Evaluation: The last section of the session consists of short questions based on the

learning tasks to check the understanding of students.

• Handouts: Additional information, which can be used in the classroom while teaching or

later for students‟, further learning. Handouts are used to provide extra information

related to the session topic that cannot fit into the session time. The students to study

PST 05208 Pharmaceutics Theory & Compounding NTA Level 5 Semester 2 Facilitator Guide

material on their own and to refer to them after the session can use handouts. Sometimes,

a handout will have questions or an exercise for the participants including the answers to

the questions.

Instructions for Use and Facilitators Preparation

• Tutors are expected to use the module as a guide to train students in the classroom and

skills laboratory

• The contents of the modules are the basis for teaching and learning dispensing.

• Use the session contents as a guide

• The tutors are therefore advised to read each session and the relevant handouts and

worksheets as preparation before facilitating the session

• Tutors need to prepare all the resources, as indicated in the resource section or any other

item, for an effective teaching and learning process

• Plan a schedule (timetable) of the training activities

• Facilitators are expected to be innovative to make the teaching and learning process

effective

• Read the sessions before facilitation; make sure you understand the contents in order to

clarify points during facilitation

• Time allocated is estimated, but you are advised to follow the time as much as possible,

and adjust as needed

• Use session activities and exercises suggested in the sessions as a guide

• Always involve students in their own learning. When students are involved, they learn

more effectively

• Facilitators are encouraged to use real life examples to make learning more realistic

• Make use of appropriate reference materials and teaching resources available locally

Preparation with Handouts and Worksheets

• Go through the session and identify handouts and worksheets needed for the session

• Reproduce pages of these handouts and worksheets for student use while teaching the

session. This will enable students to refer to handouts and worksheets during the session

in the class. You can reproduce enough copies for students or for sharing

• Give clear instructions to students on the student activity in order for the students to

follow the instructions of the activity

• Refer students to the specific page in the student manual as instructed in the facilitator

guide

Using Students Manual When Teaching

• The student manual is a document, which has the same content as the facilitator guide,

which excludes facilitator instructions and answers for exercises.

PST 05208 Pharmaceutics Theory & Compounding NTA Level 5 Semester 2 Facilitator Guide

• The student manual is for assisting students to learn effectively and acts as a reference

document during and after teaching the session

• Some of the activities included in facilitator guide are in the student manual without

facilitator instructions

PST 05208 Pharmaceutics Theory & Compounding NTA Level 5 Semester 2 Facilitator Guide

Abbreviations/Acronym

CUHAS Catholic University of Heal and Allied sciences

E.L.C.T Evangelical Lutheran Church in Tanzania

HKMU Hurbert Kairuki Memorial University

ICP Increased Intra Cranial Pressure

JSI John Snow Inc

KCMC Kilimanjaro College of Medical Sciences

LZHRC Lake zone Health Recourse Centre

MoHCGC Ministry of Health, Community development, Gender, Elderly and

children

MUHAS Muhimbili University of Health and Allied Sciences

NACTE National Council For Technical Education

RuCU Ruaha Catholic University

SIBS Spring Institute of Business and Science

SLF Saint Luke Foundation

USP United States Pharmacopoeia

MOsmol Milliosmolarity

mEq Milliequivalent

NTP Normal Temperature and Pressure

LAF Laminar Air Flow

TPN Total Parenteral Nutrition fluids

WHO World Health organization

PST 05208 Pharmaceutics Theory & Compounding NTA Level 5 Semester 2 Facilitator Guide

xii

Session 1: Introduction to Sterile Pharmaceutical Preparations

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Define sterile pharmaceutical products.

• Explain categories of sterile pharmaceutical Products.

• List qualities of sterile pharmaceutical products.

• Explain the role of aseptic techniques in assuring quality in pharmaceutical production

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

• Handout 1.1: Categories of Sterile Pharmaceutical products & medical devices

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

2 10 Minutes Presentation Definition of Sterile Pharmaceutical Products

25 Minutes Presentation Classification Categories of Sterile

Brainstorming Pharmaceutical Products

4 35 Minutes Presentation Qualities of Sterile Pharmaceutical Products

35 Minutes Presentation General Methods of Sterilizing Pharmaceutical

Buzzing Products

6 05 Minutes Presentation Key Points

7 05 Minutes Presentation Evaluation

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Definition of Sterile Pharmaceutical Products (10 minutes)

• Sterile pharmaceutical products refer to pharmaceutical products that are free from any viable

microorganisms, these are pharmaceutical products from which viable micro-organisms must be

totally absent.

• The production of sterile products requires special care and attention in order to eliminate

microbial and particulate contamination at all stages of manufacture and wherever possible also

includes a terminal sterilization process.

STEP 3: Categories of Sterile Pharmaceutical Products (25 minutes)

Activity: Brainstorming (10 minutes)

Ask students to brainstorm on the following question:

• What are the classification categories of sterile pharmaceutical products?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Not all pharmaceutical products need to be sterile. Sterility is insisted on the following products:

o Parenterally administered products e.g. injections, irrigations, ophthalmology products etc.

o Pharmaceutical products that come into direct contact with broken skin/mucous membrane or

internal organs e.g. certain instruments, sutures, surgical dressings etc.

• These products are required to be prepared and maintained in a sterile state until used.

Handout 1.1 Categories of Sterile Pharmaceutical products & medical devices

STEP 4: Qualities of Sterile Pharmaceutical Products (35 minutes)

Activity: Buzzing (10 minutes)

Ask students to brainstorm on the following question:

• What are the qualities of sterile pharmaceutical products?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• All products intended for sterilization should be manufactured under clean conditions and

therefore will be of low microbial content (bio burden) prior to sterilization.

• Sterile formulations must meet the following standard of quality:

o Should be sterile

o Free from particulate contaminants

o Free from pyrogen

o Should be physically and chemically stable

o Should have the same pH as the blood; (isohydric means the same concentration of H+

(Hydrogen ions) or pH = 7.38

o Same Osmotic pressure as blood plasma (isotonic)

STEP 5: Role of Aseptic Technique in Assuring Quality in Pharmaceutical

Production (40 minutes)

Activity: Brainstorming (5minutes)

Ask students to brainstorm on the following question:

• What are the roles of aseptic techniques in assuring quality in pharmaceutical production?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• This is a method of handling sterile materials by employing techniques, which minimize the

chances of microbial contamination in order to obtain the sterile products.

• The followings are the roles of aseptic techniques in assuring the quality in pharmaceutical

production;

o To minimize and reduce the risks of contamination

o To disinfect working area, equipment and ingredients in order to attain sterility

o To prevent access of viable micro-organisms and particulate contamination during preparation

and testing of pharmaceutical products

STEP 6: Key Points (5 minutes)

• Sterile formulations must meet the following standard of quality: remained sterile, free from

particulate contaminants, free from pyrogen, been physically and chemically stable, should have

the same pH as the blood and same Osmotic pressure as blood plasma (isotonic)

• The production of sterile products requires special care and attention in order to eliminate

microbial and particulate contamination at all stages of manufacture and wherever possible also

includes a terminal sterilization process.

STEP 7: Evaluation (5 minutes)

• What is sterile pharmaceutical products

• What are the roles of aseptic techniques in assuring quality in pharmaceutical production?

References

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011). Tanzania

Pharmaceutical Handbook (2nd ed.). Dar es salaam.

A. J. Winfield, J. A. R., I. Smith. (2009). Pharmaceutical Practice (4th ed.) British

Britain, R. P. S. o. G. (1994). The Pharmaceutical Codex (12 ed.). London: London Pharmaceutical

Press.

Handout 1.1. Categories of Sterile Pharmaceutical products & medical devices

SN Types/Categories Examples

1. Injections • Intravenous infusions

• Intravenous additives

• Total Parenteral nutrition (TPN) fluids

• Small-volume injections

• Small-volume oily injections

2. Non-injectable sterile fluids • Non-injectable water, (Sterile water for

irrigation)

• Urological irrigation solutions,

• Peritoneal dialysis solutions,

• Haemodialysis solutions,

• Inhaler solutions

3. Ophthalmic preparations • Eye drops

• Eye lotions

• Eye ointments

• Contact lens solutions

• Wetting solutions

• Cleaning solutions

• Soaking solutions

4. Intravenous additives • Potassium chloride

• Lidocaine (lignocaine)

These are sterile drugs or additives

• Heparin

regularly added to infusions

• certain vitamins

immediately before administration.

• Antimalarial injection, eg. Quinine injection

• Antibiotics.

5. Surgical dressings • Paraffin gauze dressing

• Semipermeable adhesive dressing

• Absorbent cotton wool

• Elastic adhesive dressing

• Plastic wound dressings

• Absorbent cotton gauze

• Gauze pads

• Absorbent viscose wadding

6. Implants • Small, sterile cylinders of drug, E.g.

Hormones.

Defn: Implants are small, sterile

cylinders of drug, inserted beneath

the skin or into muscle tissue to

provide slow absorption and

prolonged action therapy.

7. Absorbable haemostats • Oxidized cellulose

• Absorbable gelatin sponge

Defn: consist of a soft pad of solid

• Human fibrin foam

material packed around and over the

• Calcium alginate.

wound that can be left in situ and

absorbed by body tissues over a

period of time, usually up to 6 weeks

and to act as a matrix for complete

blood clotting.

8. Surgical ligatures and sutures Sterilized surgical catgut

Defn: These are strands of material This consists of absorbable strands of collagen

used to tie off blood or other vessels derived from mammalian tissue, particularly the

(ligature) and to stitch wounds intestines of sheep.

(suture) in surgery.

Non–absorbable Sutures and ligatures; e.g.

linen, nylon, silk and polypropylene

9. Instruments and equipment Instruments that may be required in a sterile condition

includes syringes (glass or plastic disposable), needles,

giving sets, metal surgical instruments (e.g.

scalpels, scissors, forceps), rubber gloves, catheters,

etc

Equipment such as pressure transducers,

pacemakers, kidney dialysis equipment, incubators,

Respirator parts, medical devices and endoscopes.

Session 2: Aseptic Processing

Total Session Time: 60 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give introduction of aseptic processing.

• Explain concept of aseptic processing

• Identify basic rules for effective aseptic processing

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

• Figure.2. 1: Aseptic techniques

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

15 Minutes Presentation Introduction to Aseptic Processing.

Brainstorming

10 Minutes Concept of Aseptic Processing

Presentation

Buzzing

4 20 Minutes Presentation Basic Rules for Effective Aseptic Processing

6 05 Minutes Presentation Key Points

7 05 Minutes Presentation Evaluation

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (05 Minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Introduction to Aseptic Processing (15 minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What is aseptic processing?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

Aseptic processing

• Is the processing and packaging of a commercially sterile product into sterilized containers

followed by hermetic sealing with a sterilized closure in a manners that prevents viable

microbiological recontamination of the sterile product.

• It require careful control of the aseptic environment, of personnel practices and procedures,

sterilization of equipment and components, extensive environmental monitoring, and many other

controls.

• The number of controls required and the severe consequences of control failure make aseptic

processing one of the highest-risk pharmaceutical processes. Quality risk management is an essential

tool in ensuring product quality.

STEP 3: Concept of Aseptic Processing (10 minutes)

Activity: Brainstorming (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What are the concepts of aseptic processing?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Suitable measures must be taken to ensure the microbiological quality of pharmaceutical

preparations during manufacturing but also during packaging, storage and distribution is

maintained

• The requirements necessary to achieve strict asepsis include:

o sterile starting materials

o Sterile equipment

o Controlled environment

o Sterile containers

o Suitable technique by trained personnel

Figure.2. 1: Aseptic techniques

processing operation by Ranjith Kumar kankala (2012)

STEP 4: Basic Rules for Effective Aseptic Processing (20 minutes)

• Use a „no touch‟ technique whenever possible.

o Handle small articles with sterile forceps and, when sterile apparatus must be touched, handle

as distant as possible from the part which will come into contact with a sterile liquid or solid,

this rule applies even though sterile gloves may be worn

• Reduce air disturbances to a minimum

o Standard procedures should be designed to minimize movement of personnel within the clean

room. Objects should be positioned within reach under the laminar air flow cabinet. Sharp

and sudden movements should be avoided.

• Consider the arrangement of objects under the laminar air flow (LAF)

o Clean air should not flow over dirty articles to contaminate sterile articles, the cabinet should

not be loaded with unnecessary equipment, and materials required should be carefully

selected and arranged before beginning the procedure.

• Refuse to be distracted

o No interruption should be allowed until a set procedure has been completed.

STEP 4: Key Points (5 minutes

• Aseptic process requires careful control of the aseptic environment, of personnel practices and

procedures, sterilization of equipment and components, extensive environmental monitoring and

many other controls.

• The number of controls required and the severe consequences of control failure make aseptic

processing one of the highest-risk pharmaceutical processes. Quality risk management is an

essential tool in ensuring product quality.

STEP 5: Evaluation (5 minutes)

• What is aseptic processing?

• What is the requirements necessary to achieve strict asepsis

References

Nelson, Philip (1993). Principles of Aseptic Processing and Packaging (3 ed.). USA: GMA Science

and Education Foundation. Retrieved 19 April 2018. Sudan

D., David, Jairus R. (2013). Handbook of aseptic processing and packaging. Graves, Ralph H.,

Szemplenski, Thomas. Boca Raton: Taylor & Francis.

Hargreaves, Paul. (2018)"Recommendation on the Validation of Aseptic Processes". Pharmaceutical

Inspection Co-Operation Scheme. PIC/S. Retrieved 8 May 2018.New York

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011). Tanzania

Pharmaceutical Handbook (2nd ed.). Dar es salaam:

Session 3: Requirements for Preparation of Sterile

Pharmaceutical Products

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

 Explain premise requirements for sterile production.

 Explain personnel requirements for sterile production.

 Explain raw materials requirements for sterile production.

 Explain documentation requirements for sterile production.

 Explain equipment requirements for sterile production.

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

30 Minutes Presentation

Buzzing Premise Requirements for Sterile Production.

30 Minutes Presentation

Brainstorming Personnel Requirements for Sterile Production.

15 Minutes Presentation

4 Raw Materials Requirements for Sterile Production.

Buzzing

15Minutes Presentation

5 Documentation Requirements for Sterile Production.

Brainstorming

15 Minutes Presentation Equipment Requirements for Sterile Production.

Brainstorming

7 05 Minutes Presentation Key Points

8 05 Minutes Presentation Evaluation

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Premise Requirements for Sterile Production (30 minutes)

• The quality of infusions produced will depends very much on the degree of care taken during its

preparation.

• Each step in the production process is a possible source of contamination to the manufactured

product.

• Hence, Manufacture of sterile preparations (e.g. infusions) needs special requirements to

minimise the risks of particulate, microbial and pyrogens contamination.

• Therefore, production of sterile preparations needs environmental control of particulate and

microbial contamination, so as to reduce the introduction, generation, and retention of

contaminants during preparation.

• Well maintained premises:

o The facilities for the manufacture of sterile products should be designed for near to perfect

level of cleanliness.

o The maximum degree of cleanliness must be achieved in the aseptic filling rooms.

o The surrounding areas should provide a buffer area in which standards of cleanliness are only

slightly lower than the aseptic rooms.

o The prevention of contamination must be the primary objective in the design of these

facilities.

o Well-maintained premise is a good indicator that production of infusions is done in clean

environment that reduces risks of contamination to the product.

• Methods of cleansing:

o All equipment and surrounding work area must be cleaned thoroughly at the end of the

working day.

o After thorough cleaning, all surfaces should be disinfected, at least in the aseptic area.

o An effective liquid disinfectant should be sprayed or wiped on all surface.

o Irradiation from UV lamps properly located will further reduce the viable microorganisms on

surfaces and in the air.

• Production Flow pattern:

o The facility should be designed in such a way that it provides a continuous flow of production

activities.

o A change area has to be available before entering the facilities to allow change of street

clothes into the appropriate production garments and gear.

o There should then be a continuous process from supply storage to compounding of product,

filling, sealing, sterilisation, labelling/packaging and finally to storage of the finished product.

STEP 3: Personnel Requirements for Sterile Production (30 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

• What are the personnel requirements for sterile production

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Should be adequately trained and motivated e.g. Equipped with basic understanding of

pharmaceutical technology, microbiology and hygiene.

• They should be aware of the role that every movement has, in determining the quality of the final

product. e.g. Aware of the sources of contamination.

• Appropriate protective clothing should be worn. e.g. Boots, coats, caps, gloves, hats, and mask.

• Personnel working in aseptic areas should be required to follow laid down preparatory

procedures.

o These include removing outside street clothing, scrubbing the hands and arms thoroughly

with disinfectant soap, and wearing of prescribed uniforms.

o Uniforms usually consist of sterile overalls, hats, facemasks and shoe covers. Sterile rubber

gloves also may be required.

o Uniforms are worn to control emission of particulate matter, which is continually shedding

from body surfaces.

o Aware of the hazards, which can be caused by using products of poor standards.

o Behaviour like smoking, eating, drinking, chewing, attending phone calls, in- and out-

movements and any other activity that influence the product quality while in production

processes are restricted

STEP 4: Raw Materials Requirements for Sterile Production (15 minutes)

• All materials purchased for use in compounding and dispensing

o Should be of suitable quality and obtained from a licensed or reliable source.

o „In house‟ check of quality may be made on starting materials.

o Materials should be fully identifiable and carry a clear batch identification and expiry date.

o Appropriate storage conditions should be maintained and out-of-date stock safely disposed

o Should be pyrogens free

STEP 5: Documentation Requirements for Sterile Production (15 minutes)

• All compounding procedures should be fully documented and the record should include the

following details:

o The name of the product.

o A written master formula & the working formula of the batch being prepared.

o The method of preparation

o The names, quantities and identification of each starting material

(Supplier, batch number and date received)

o The date of manufacture.

o The appropriate container and closure.

o The required storage conditions.

o A copy of the label.

STEP 6: Equipment Requirements for Sterile Production.(15 minutes)

Activity: Buzzing (5 minutes)

Ask students to brainstorm on the following question:

• What are equipment requirements for sterile production?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Equipment requirements for sterile production:

o Should be of appropriate design,

o Suitable, well maintained and adequate for the work to be undertaken.

o All equipment must be maintained in accurate working order

o Checked for cleanliness prior to each use.

o Should be simple to use.

o Should be durable

o Spare parts should be available

o Service free

o Cheap

o Should be stainless

STEP 7: Key Points (5 minutes)

• The quality of sterile pharmaceuticals produced will depends very much on the degree of care

taken during its preparation; each step in the production process is a possible source of

contamination to the manufactured product.

• All materials purchased for use in compounding and dispensing, should be of suitable quality and

obtained from a licensed or reliable source, „In house‟ check of quality may be made on starting

materials.

• All compounding procedures should be fully documented and the record should include the

details like the name of the product, a written master formula & The working formula of the batch

being prepared and the method of preparation the names, quantities and identification of each

starting material (supplier, batch number and date received)

STEP 8: Evaluation (5 minutes)

• What are premises requirements for sterile production?

• What are raw materials requirements for sterile production?

• What are documentation requirements for sterile production?

References

Nally, J.D., ed. (2007). Good Manufacturing Practices for Pharmaceuticals (6th ed.). CRC Press.

p. 424. ISBN 9781420020939. New York

FDA Guidelines (2004) "Guidance for Industry Sterile Drug Products by Aseptic Processing,

Current Good Manufacturing Practices,"

A. J. Winfield, J. A. R., I. Smith. (2009). Pharmaceutical Practice (4th ed.). British

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011). Tanzania

Pharmaceutical Handbook (2nd ed.). Dar es salaam:

Session 4: Percutaneous Absorption

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

 Explain percutaneous Absorption

 Explain factors affecting percutaneous absorption

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

50 Minutes Presentation

2 Percutaneous Absorption

Brainstorming

55 Minutes Presentation

3 Factors Affecting Percutaneous Absorption

Buzzing

4 05 Minutes Presentation Key Points

5 05 Minutes Presentation Evaluation

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Percutaneous Absorption (50 minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What is percutaneous absorption?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Percutaneous absorption is the term used to describe the penetration of a substance through the

skin and subsequent movement into the systemic circulation.

• For drugs applied topically for therapeutic purpose, its necessary that:

o The medicament is released from the base

o Adequate amount of drug penetrate the skin

o Sufficient concentration of the drug is maintained at the site of action.

• In some instance, skin penetration of medicament is not necessary for a topical applied

medicament

• A surface film of the active medicament is necessary for this instance. e.g. for medicament

applied topically purposely for:

o Skin protection (against sunlight or moisture loss

o For emollient effect

o For antimicrobial activities in skin disinfection

• When skin penetration for local activity is the aim, the active substance should be retained for as

longer as possible in the viable epidermis and dermis with minimal elimination by systemic

circulation.

• Therefore, by regarding skin as the route of drug administration, it‟s important to know the

mechanism by which medicaments penetrates the skin barrier.

• Structure of skin

o The skin is divided into three layers:

 epidermis

 dermis

 hypodermis (subcutaneous fat layer)

• Epidermis

o Is about 110µm thick

o Is pierced by hair follicles & sebaceous gland

o It is non vascular

o The outer layer of the epidermis is called stratum corneum

o The stratum corneum is transparent, tough coherent & viscoelastic properties.

o The stratum corneum is composed of dead cells each packed with keratin.

o Resistance to the diffusion of chemicals is greater in stratum corneum (sc) than in the

underlying living skin tissue.

o SC is the rate-limiting barrier to movement of materials & responsible tissue for

impenetrability of the skin.

o However the is not an absolute barriers and trace amount of penetrants can be detected; eg

nickel, chromium ions, parathion & toxic gases.

o The thickness of sc varies. It is thick on the plantar & palmar areas and thin behind the ear and

on the eyelid.

o Cells are formed through mitosis at the basale layer

o The daughter cells move up the strata changing shape and composition as they die due to

isolation from their blood source

o The cytoplasm is released and the protein keratin is inserted.

o They eventually reach the corneum and slough off (desquamation).

o This process is called keratinization and takes place within about 27 days.

o This keratinized layer of skin is responsible for keeping water in the body and keeping other

harmful chemicals and pathogens out, making skin a natural barrier to infection.

• Dermis

o The dermis is the layer of skin beneath the epidermis that consists of connective tissue and

cushions the body from stress and strain.

o The dermis is tightly connected to the epidermis by a basement membrane.

o It also harbours many Mechanoreceptor/nerve endings that provide the sense of touch and

heat.

o It contains the hair follicles, sweat glands, sebaceous glands, apocrine glands, lymphatic

vessels and blood vessels.

o The blood vessels in the dermis provide nourishment and waste removal from its own cells as

well as from the Stratum basale of the epidermis.

• Hypodermis

o The hypodermis lies below the dermis

o Its purpose is to attach the skin to underlying bone and muscle as well as supplying it with

blood vessels and nerves.

o The main cell types are fibroblasts, macrophages and adipocytes (the hypodermis contains

50% of body fat). Fat serves as padding and insulation for the body.

Figure: 1.4. Structure of skin

Source: Human Anatomy by Matthew Hoffman, MD (2014)

STEP 3:Factors Affecting Percutaneous Absorption (55 minutes)

Activity: Brainstorming (20 minutes)

Ask students to brainstorm on the following question:

• What are factors affecting percutaneous absorption?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Factors affecting percutaneous absorption can be considered under three main heading

o Condition of the skin

o Physicochemical characteristics of the active substance

o Effect due to the vehicle.

• Condition of the skin.

o Damage and disease.

 Intact skin presents a barrier to absorption that can be reduced considerably when the skin

is damaged or is in a disease state.

 Skin can be damaged by:

• Dryness

• Irritation

• Allergic reaction

• abrasion

o Injured skin has increased percutaneous than intact skin.

• Age

o Percutaneous absorption of infants is higher than in adult to a given medicament due to

 large surface area than that of adult

 Partial developed epidermal drug metabolizing enzymes.

o Old age can also affect permeability of the skin through change in the elasticity, ultrastructure,

chemical composition & barrier properties.

• Temperature & humidity;

o Absorption is influenced by environmental factors such as skin temperature & surface

humidity,

o Diffusion can be accelerated by raising surface temperature e.g. by occlusion

• Skin site

o Fick‟s law of diffusion states that the diffusion of a solute will be inversely proportional to the

thickness of stratum corneum.

o In the plantar & palmar the SC is thick & absorption rate is low than in thin thickness like on

face & behind the ear.

• Hydration.

o Absorption of active substance is enhanced as the skin become more hydrated.

o Topical medicament with occlusive effect has high absorption rate than the non-occlusive

• Miscellaneous aspects

o The application of vasoconstrictor such as steroids on the skins surface may slow penetration

because of the reduced blood supply.

STEP 4: Key Points (5 minutes

• Percutaneous absorption is the term used to describe the penetration of a substance through the

skin and subsequent movement into the systemic circulation.

• For drugs applied topically for therapeutic purpose, it‟s necessary that: the medicament is released

from the base, adequate amount of drug penetrate the skin and sufficient concentration of the drug

is maintained at the site of action.

• Factors affecting percutaneous absorption include condition of the skin, physicochemical

characteristics of the active substance and effect due to the vehicle.

STEP 5: Evaluation (5 minutes)

• What is percutaneous absorption?

• What are factors affecting percutaneous absorption?

References

Bronaugh, R.L.; Stewart, R.F. (1985). "Methods for percutaneous absorption studies. IV. The flow

through diffusion cell". J. Pharm. Sci. 74: 64–7. doi:10.1002/jps.2600740117.Sudan

Mahato RA. (2006) Pharmaceutical dosage forms & drug delivery‟‟ Published by CRS press, Taylor

& Froncrs Group,6000 Broken Sound Parkway, Sute 300, Boca Raton, 196-197.New York

A. J. Winfield, J. A. R., I. Smith. (2009). Pharmaceutical Practice (4th ed.) British

Britain, R. P. S. o. G. (1994). The Pharmaceutical Codex (12 ed.). London: London

Session 5: Semi Solid Preparations

Total Session Time: 120 Minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

 Define semi – solid pharmaceutical preparations

 List ideal properties of semi – solid preparations

 Explain rational approaches to topical formulation

 List treatment target for semisolid preparations

 Explain components of semi – solid pharmaceutical preparations

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

10 Minutes Presentation Definition of Semi- Solid Pharmaceutical

Buzzing Preparations

3 15 Minutes Presentation Ideal Properties of Semi – Solid Preparations

4 15 Minutes Presentation Rational Approaches to Topical formulation

35 Minutes Presentation

5 Treatment Target for Semisolid Preparations

Brainstorming

30 Minutes Presentation Components of Semi – Solid Pharmaceutical

Preparations

7 05 Minutes Presentation Key Points

8 05 Minutes Presentation Evaluation

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Definition of Semi – Solid Preparations (10 minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What are semi – solid pharmaceutical preparations?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Pharmaceutical semisolid preparations: Are the topical products intended for application on

the skin or accessible mucous membranes to provide localized and sometimes systemic effects at

the site of application, it is a preparations designed to exert local activity when applied to the

skin or mucous membranes

• The main medicinal applications of semi-solids pharmaceutical preparations are as protective,

emollient, and therapeutic agents, these semi-solid pharmaceutical preparations for external

application are: ointments, pastes, creams, poultices/cataplasms and gels.

STEP 3: Ideal Properties of Semi – Solid Preparations (15 minutes)

• Physical properties:

o Smooth texture

o Elegant in appearance

o Non dehydrating

o Non gritty

o Non greasy and non-staining

o Non hygroscopic

• Physiological properties:

o Non irritating

o Do not alter membrane / skin functioning

o Miscible with skin secretion

o Have low sensitization index

• Application properties:

o Easily applicable with efficient drug release.

o High aqueous washability.

• Storage properties:

o Should be stored at temperatures not exceeding 25°c unless otherwise authorized.

o They should not be allowed to freeze and must be stored in a well-closed container or, if the

preparation contains water or other volatile ingredients, store in an airtight container.

o The containers are preferably collapsible metal tubes from which the preparation may be

readily extruded.

o If the preparation is sterile, store in a sterile, airtight, tamper-proof container.

STEP 4: Rational Approaches to Topical Formulation (15 minutes)

• There are three main methods for a successful formulation of topical dosage form

o By manipulating barrier function of skin;

 Topical antibiotics and antibacterials help damaged barrier to avoid infections

 Sunscreen and the horny layer protect viable tissues from u.v. radiations

 Emollients restore pliability to desiccated horny layer

o By directing drugs to the viable skin tissues without using oral, systemic or other routes of

therapy

o By using skin delivery for systemic treatment

 e.g. transdermal therapeutic systems provide systemic therapy for motion sickness,

angina and hypertension

STEP 5: Treatment Target for Semi – Solid Preparations (35 minutes)

Activity: Brainstorming (15 minutes)

Ask students to brainstorm on the following question:

• What are treatment target for semi – solid preparations?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Five main target regions:

o Skin surface, horny layer, viable epidermis and upper dermis, skin glands, and systemic

circulation.

• Surface treatment

o Care for skin surface is mainly by cosmetic application, that form protective layer, or attack

bacteria and fungi

o Sunscreens, barriers that hinder moisture loss, antimicrobials and insect repellants)

• Stratum corneum treatment

o Main therapies aimed at the horny layer improve emolliency by raising water content or

stimulating sloughing

o E.g. keratosis, exfolients such as salicylic acid

• Skin appendage treatment

o Antiperspirants (aluminium) reduce hyperhidrosis of sweat glands

o Exfolients (e.g. salicylic acid, tretinoin (retinoic acid), benzoyl peroxide) for acne

o Topical antimicrobials, depilatories etc.

• Viable epidermis and dermis treatment

o Diseases can be treated provided that the preparation efficiently delivers drug to the receptor

o E.g. anti-inflammatory drugs (steroids & non steroids), antitumor (e.g. methotrexate, 5-

fluorouracil) anesthetics (e.g. benzocaine), antihistamines

• Systemic treatment via percutaneous absorption

o In recent years considerable scientific work has led to the skin route being used to treat several

conditions by means of transdermal patches

o E.g. motion sickness (hyoscine), angina (nitroglycerin)

STEP 6: Components of Semi – Solid Pharmaceutical Preparations (30 minutes)

• Antioxidant

o Prevents or slows oxidation of other components

o Examples: Tocopherol, butylated hydroxy toluene, or a reducing agent such as ascorbic acid.

• Base

o Major classes or types of formulation compositions based on composition and physical

properties.

o Examples: Please refer to bases chapter.

• Buffer

o Acid-conjugate base mixture employed to control pH and therefore control ionization state of

drug and impart stability

o Examples: Citrate, phosphate, tartarate

• Chelating agent

o Have the ability to bind metal ions; prevents auto-oxidation phenomena frequently catalyzed

by metal ions and enhances action of preservatives by binding iron and copper ions essential

to microbial growth.

o Example: EDTA, citric acid

• Emulsifying agent: Reduces surface tension of two phases in an emulsion, preventing coalescence

of individual phases.

o Example: Detergent, emulsifying wax (detergent treated wax), cetostearyl alcohol,

polysorbate 20.

• Humectant: Promotes retention of water in a mixture Glycerin, propylene glycol, polyethylene

glycols (low MW).

• Permeation enhancer: Facilitates diffusion process of active ingredient across the stratum

corneum by chemical modification.

o Example: Ethanol, oleic acid, propylene glycol, polyethylene glycol (400)

• Preservative:

o Prevents or slows microbial growth; may be one of 4 major compound types: acid, alcohol,

quaternary ammonium compounds, or organic mercurial.

o Example: Acid: benzoic acid; alcohol: phenylethyl alcohol; quaternary ammonium: stearyl

dimethyl benzyl ammonium chloride; organic mercurial: thimerosal.

• Thickening agent: Increase viscosity; may be natural, semi-synthetic, or synthetic.

o Example: Natural: cellulose, pectin; semi-synthetic: methylcellulose, (sodium)

carboxymethylcellulose; synthetic: Carbopol

STEP 7: Key Points (5 minutes)

• Pharmaceutical semisolid preparations: Is the topical products intended for application on the skin

or accessible mucous membranes to provide localized and sometimes systemic effects at the site

of application, it is a preparations designed to exert local activity when applied to the skin or

mucous membranes

• Ideal properties of semi – solid preparations include, physical properties, physiological properties,

application properties and storage properties

STEP 8: Evaluation (5 minutes)

• What are treatment target for semi – solid preparations?

• What are semis – solid pharmaceutical preparations?

References

Britain, R. P. S. o. G. (1994). The Pharmaceutical Codex (12 ed.). London: London Pharmaceutical

Press.

Winfield, J. A. R., I. Smith. (2009). Pharmaceutical Practice (4th ed.)British

Wolverton, SE. Comprehensive Dermatologic Drug Therapy. WB Saunders. 2001. pp 563-572.New

York

Singh Malik, D; Mital, N; Kaur, G (2016). "Topical drug delivery systems: a patent review". Expert

opinion on therapeutic patents. 26 (2): 213–28. Sudan

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011). Tanzania

Pharmaceutical Handbook (2nd ed.). Dar es salaam.

Session 6: Reference and Formula in Pharmaceutical

production

Total Session Time: 120 minutes + 4 hours of Practical

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Define monographs

• List different types of references used in Pharmaceutical production

• Identify Formula for Pharmaceutical preparations

• Reduce or enlarge official formula to obtain required formula for compounding

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

• Worksheet 6.1: Take Home Assignment

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

10 Minutes Presentation Definition of Drug Monographs

Buzzing

25 Minutes Presentation Types of References Used in Pharmaceutical

3 Production

Demonstration

20 Minutes Presentation Identification of Formula for Pharmaceutical

Demonstration Preparations

40 Minutes Reduce or Enlarge Official Formula to Obtain

Presentation

5 Required Formula for Compounding

Group Discussion

6 05Minutes Presentation Key Points

7 05 Minutes Presentation Evaluation

8 10 Minutes Presentation Take home assignment

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Definition of Drug monographs (10 minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What are drug monographs?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Drug monograph refers to a publication that specifies for a drug ( or class of related drugs) the

kind and amount of ingredients and may contain the conditions and imitations for which it may be

offered, directions for use, warnings, and other information contained in its label

• Drug monograph may also contain important information concerning interactions with other

drugs

STEP 3: Types of References Used in Pharmaceutical Production (25 minutes)

• British Pharmacopoeia (BP)

o Book of standards of purity and strength for medical substances, products, dressings, etc.

together with „official‟ assays and tests.

• British Pharmaceutical Codex (BPC) 1973

o Provides a source of standards for some extemporaneous preparations not included in the BP

and is now incorporated into the Pharmaceutical Codex.

• Pharmaceutical Codex (PCx) 1979

o The PC is an encyclopedia of drug information and includes entries on diseases and

conditions, aspects of pharmaceutics, surgical dressings and veterinary information as well as

the formulae for medicines

• European Pharmacopoeia (EP or Ph. Eur).

o Prepared under the auspices of the council of Europe and was created to permit free

circulation of drugs within the European community.

• International Pharmacopoeia (IP)

o Publication of the World Health Organization (WHO) providing recommended standards for

international use.

• United States Pharmacopoeia (USP) and National Formulary (NF)

o The official standard reference of the United States of America (USA). There is a companion

volume of dispensing information (USPDI).

• European Pharmacopoeia (EP or Ph. Eur).

o Prepared under the auspices of the council of Europe and was created to permit free

circulation of drugs within the European community.

• International Pharmacopoeia (IP)

o Publication of the World Health Organization (WHO) providing recommended standards for

international use.

• United States Pharmacopoeia (USP) and National Formulary (NF)

o The official standard reference of the United States of America (USA). There is a companion

volume of dispensing information (USPDI).

• Martindale: The Extra Pharmacopoeia

o An authoritative reference book on drugs and medicines in current use throughout the world.

Martindale provides detailed information on nomenclature, physical and pharmaceutical

properties, adverse effects, actions and uses, etc.

• Pharmaceutical Handbook

o A reference manual for practitioners and students of pharmacy and the allied professions.

Information such as „The preparation and supply of medicines‟, „methods of sterilization,‟

„nomenclature of organic compounds‟, desirable body weights and calculation of body surface

areas which are useful data relevant to pharmacy.

• British National Formulary (BNF)

o Provides general guidance for prescribers together with the special requirements of particular

groups of patient, e.g. the very young, the elderly, pregnant women and patient with renal or

hepatic failure.

o Contains notes on drugs and preparations classified under the diseases and conditions to be

treated.

o Information on indications, contraindications, cautions, side effects and doses are given for

each drug listed.

o A formulary for commonly used „official‟ extemporaneous preparations and information on

drug interactions, cautionary and advisory labels, etc. for the pharmacists are included.

STEP 4: Identification of Formula for Pharmaceutical Preparation (20 minutes)

• After comprehended the request in the prescription, a compounder has to identify the correct

formula from the reference book

• The correct formulas from the reference book can be obtain through the following ways:

o Find the name of the pharmaceutical preparation to be compounded through table of

contents of the reference book and go to formulation, e.g. solution.

o The formulation in the content indicates the page where the respective formula is

indicated.

o Find the name of the pharmaceutical preparation to be compounded through the index of

the reference book

o The index indicates the number of page where the respective formula is indicated

Below are official formulas obtained from the reference book (TPH) under the indicated table

of content of the book.

• COMPOUND BENZOIC ACID OINTMENTPCx (Syn.Whitfield‟s Ointment)

Benzoic acid, in fine powder……………………………… 6.0 g

Salicylic acid, in fine powder……………………………….. 3.0 g

Emulsifying ointment …………………………………….. 91.0g

• SULPHUR OINTMENT PCx.

Precipitated sulphur, finely sifted…………………………… 10.0 g

Simple ointment…………………………………………… 90.0 g

Activity: Demonstration (10 minutes)

DIVIDE students in small manageable groups.

PREPARE formula from a reference book for demonstration

POSITION students so that everyone can see and hear

REVIEW steps of that skill with students using a reference book

REFER students to the Tanzania Pharmaceutical Handbook (TPH)

DEMONSTRATE the procedure of identifying a formula from a reference book

ALLOW one student from each group to do a return demonstration and let others comment

on it

CLARIFY and SUMMARIZE the procedures to identify a Formula for Pharmaceutical

Preparation

INFORM the students that “every student will practice in the laboratory under supervision

until is competent”

STEP 5: Reduction and Enlarging of Official Formula to Obtain Amount of Each

Ingredient Required for Compounding (40 minutes)

• Reducing and enlarging formula are calculations performed when the required amounts of

medicines (Prescribed/ordered) deviate from the official formula in a reference book.

o Obtaining the amount of each ingredient required for compounding, the figures of the official

formula are multiplied by a factor which is determined by the following proportion:-

Total amount of the official = quantity of each ingredient in the official formula

Total amount required x

(x = quantity of each ingredient in the required amount)

i.e.

x = total amount required × Quantity of each ingredient in the official formula

Total amount of official formula

Thus the factor is determined by the ratio:

Total amount required .

Total amount of official formula

Summary on obtaining the amount for each ingredient in the required amount (x):

x = FACTOR × quantity of each ingredient in the official formula

To Determine Amount of Each Ingredient Required for Compounding

Activity: Small Group Discussion ( 20 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• What is the amount of each ingredient required to make 50g of Salicylic acid ointment

PCx?

REFER Students to Tanzania Pharmaceutical Handbook (2011): Chapter 2,

Formulary and list of alternatives for Pharmaceutical ingredients including water, for

reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

• Official formula given for salicylic acid ointment PCx

o Salicylic acid, finely sifted…. ……………………………………… 2.0g

o Wool alcohols………………….. …………………………………. 98.0g

Thus:

Total amount of official formula = 100g

Total amount required = 40 mL

Amount of each ingredient (x) =?

FACTOR = required amount .

Official amount

= 50gm = 0.5

100gm

Then, amount of each ingredient can be obtained as summarized in table below,

Formula Official amount Factor Required amount

Salicylic acid, finely sifted 2.0g 1.0 g

Wool alcohols 98.0g 0.5 49.0 g

• Therefore amount required for each ingredient to make 50g of Salicylic acid ointment are:

o Salicylic acid, finely sifted ………………………………………….. 1.0 g

o Wool alcohols ………………………….. ……………………………49.0g

• Official formula given for Compound zinc paste PCx. (Syn. Zinc paste)

o Zinc oxide, finely sifted ………………………..……………………. 25.0 g

o Starch, finely sifted ……………………..…………………………… 25.0g

o White soft paraffin ……………..………………..…………………… 50.0 g

• Thus:

o Total amount of official formula = 100g

o Total amount required = 20g

o Amount of each ingredient (x) =?

FACTOR = required amount .

Official amount

FACTOR = 20gm = 0.2

100gm

Then, amount of each ingredient can be obtained as summarized in table below,

Formula Official amount Factor Required amount

Zinc oxide, finely sifted 25gm 5.0 gm

Starch, finely sifted g 25gm 0.2 5.0 gm

White soft paraffin 50gm 10.0gm

• Therefore amount required for each ingredient to make 20g of Compound zinc oxide paste PCx,

o Zinc oxide, finely sifted……………….. 5.0 gm

o Starch, finely sifted …………………… 5.0gm

o White soft paraffin ……………..……… 10.0 gm

STEP 6: Key Points (5 minutes)

• A monograph is a specialist work of writing in contrast to reference works on a single subject or

an aspect of a subject, often by a single author, and usually on a scholarly subject.

• In library cataloging, monograph has a broader meaning, that of a nonserial publication complete

in one volume (book) or a definite number of volumes. Thus it differs from a serial publication

such as a magazine, journal, or newspaper.

STEP 7: Evaluation (5 minutes)

• What is a reference book?

• What are the types of references used in pharmaceutical production?

STEP 9: Take Home Assignment (10 minutes)

Activity: Take home Assignment (10 minutes)

DIVIDE students in groups or individual.

ASK the students to work on the following assignment

• Practice to calculate amount required in the following exercises as shown on page 1 and

2 of the worksheet 6.1.

ALLOCATE time for students to do the assignment and submit

REFER students to worksheet 6.1: Take Home Assignment

References

Pharmaceutical Society of Great Britain., & . Department of Pharmaceutical Sciences. (1994). The

Pharmaceutical Codex, Principles and Practice of Pharmaceutics (W. Lund Ed. 12th ed.).

London,: Pharmaceutical .

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011). Tanzania

Pharmaceutical Handbook (2nd ed.). Dar es salaam.

United States Pharmacopeial Convention. Committee of Revision. (2013). The United States

pharmacopeia (pp. v.). Rockville, Md.: United States Pharmacopeial Convention, Inc.

Worksheet 6.1: Take Home Assignment

Take home Assignment

Practice Calculations of amounts required for compounding from the official formula in the

following exercise

Questions / Instructions

1. From the following formula, calculate the quantities required to make 150 g of Hydrous wool fat

ointment PCx

Hydrous wool fat …………………………………………… 50g

Yellow soft paraffin …………………………………………. 50g

2. From the following formula, calculate the quantities required to make 5g of Paraffin ointment

PCx

Hard paraffin ……………………………………………….. 3.0 g

White beeswax ………………………………………………. 2.0 g

Cetostearyl alcohol ……………………………………………. 5.0g

White soft paraffin …………………………………………… 90.0

3. From the following formula, calculate the quantities required to make 50g of Salicylic acid and

sulphur ointment PCx

Salicylic acid, finely sifted……………………………………………. 3.0 g

Precipitated sulphur, finely sifted………………………………………3.0 g

Oily cream …………………………………………………………… 94.0 g

4. From the following formula, calculate the quantity of each ingredient required to make 1500 g of

Compound benzoic acid ointment PCx

Benzoic acid, in fine powder ………………………………………… 6.0g

Salicylic acid, in fine powder ………………………………………….3.0g

Emulsifying ointment ………………………………………………… 91.0g

5. From the following formula, calculate the quantity of each ingredient required to make 250 g of

Calamine ointment PCx

Calamine, finely sifted ………………………………………. 15.0g

White soft paraffin …………………………………………… 85.0g

6. From the following formula, calculate the quantity of each ingredient required to make 100 g of

Zinc and salicylic acid ointment PCx

Salicylic acid, finely sifted ………………………………………………….. 2.0g

Starch, finely sifted ……………………………………………….. ………… 24.0g

Zinc oxide, finely sifted ……………………………………………………… 24.0g

White soft paraffin…………………………………………………………… 50.0g

ANSWERS

1. Hydrous wool fat ……………………………………………… 75.0g

Yellow soft paraffin ……………………………………………75.0g

2. Hard paraffin ………………………………………………. 0.15 g

White beeswax …………………………………………….. 0.1g

Cetostearyl alcohol ……………………………………………. 0.25g

White soft paraffin …………………………………………… 4.5g

3. Salicylic acid, finely sifted………………………………………1.5g

Precipitated sulphur, finely sifted………………………………1.5 g

Oily cream …………………………………………………… 47.0 g

4. Benzoic acid, in fine powder ……………………………………90.0g

Salicylic acid, in fine powder ……………………………………45.0g

Emulsifying ointment ……………………………………………1365.0g

5. Calamine, finely sifted ………………………………………. 37.5g

White soft paraffin …………………………………………… 212.5g

6. Salicylic acid, finely sifted ………………………………………2.0g

Starch, finely sifted …………………………………………… 24.0g

Zinc oxide, finely sifted …………………………………………24.0g

White soft paraffin………………………………………………50.0g

Session 7: Compounding of Ointments

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

 Define ointment

 Describe procedures for preparing ointment

 Prepare ointment

 Label prepared ointment

 Dispense prepared ointment into suitable containers and closure

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

• Figure 7.1: Ointment jars.

SESSION OVERVIEW

Step Time Activity/ Method Content

1 05 minutes Presentation Introduction, Learning Tasks

2 10 minutes Presentation Buzzing Definition of Ointment

3 25 minutes Presentation Procedures for Preparing Ointment

35 minutes Presentation

4 Preparing Ointment

Demonstration

5 20 minutes Presentation Labeling of Prepared Ointment

15 minutes Presentation Dispensing Prepared Ointment into Suitable

Brainstorming Containers and Closure

7 05 minutes Presentation Key Points

8 05 minutes Presentation Evaluation

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Definition of Ointments (10 minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What is ointment?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Ointment is a viscous semisolid preparation, oily in nature used topically on a variety of body

surfaces, and it is usually applied on the skin and the mucus membranes of the eye, vagina, anus,

and nose. An ointment may or may not be medicated.

• Ointments are used as: emollients to make skin more pliable, protective barriers, vehicles in

which to medications are incorporated. They may be readily applied to the skin with inunction

(smearing or rubbing)

STEP 3: Describe Procedures for Preparing Ointments (25 minutes)

• Basic Techniques for Preparation

o Weighing

o Measuring liquids

o Size reduction

o Size separation (sieving)

o Mixing (Fusion or Trituration)

• Preparation

• Method used depends on;

o Properties of the medicaments

o Type of basis

o Quantity of ointment required

• Trituration Method

o Used when medicament to be incorporated is insoluble in the ointment basis or liquid is

present in small amount

o Involves incorporation of drug by levigation

o Used for small quantities of relatively soft ointment

o Employs a slab and a spatula of flexible metal or plastic for mixing and incorporation of

liquids or solids

o Steel spatula are suitable for most substances but should not be used for ointments containing

Hg salts, tannic acid, salicylic acid or iodine

o Insoluble powders must be finely powdered and levigated with some of the melted basis or

with a suitable liquid

o Wool fat, glycerol are good levigating agents

o Water soluble salts should be dissolved in minimum amount of water and then incorporated

with aid of small amount of lanolin

o Mortar and pestle is used if liquids are used for larger quantities of ointment

o After levigation or dissolution the concentrate is diluted geometrically with the basis, with

scrapping off of material from the sides of the mortar and pestle

o Trituration is done until the preparation is uniform

• Fusion Method

o Used for large-scale manufacturing or for ointments in which waxes or solids or high melting

points are mixed with semi-solids or oils

o Also used when large volume of water are to be incorporated

o Constituents are melted successively in decreasing order of melting point

o The fluid mixture stirred until cooled, avoiding aeration

o Crystals of fatty alcohols form (in systems with paraffin) if not well stirred

o Volatile medicaments are added when ointment has cooled below 40⁰C

o Insoluble powders in form of levigated dispersion are incorporated when ointments begin to

thicken

o Soluble, heat-stable can be dissolved in melted basis before congealing thickening

o Roller mills or colloid mills may be used to improve homogeneity to attain uniform

distribution of insoluble solids and elimination of larger particles

• Dilution of Ointment

o Dilution of stronger ointment is done when strength prescribed is not available

o Only recommended diluents should be used e.g. soft paraffin

o In tropical climates, the bases which are too soft are stiffened by addition of fats, hard paraffin, or

waxes

o This addition is permitted if active ingredients content or action is not altered

-Trituration using tile and spatula – Trituration using motor and pestle

Electric Mortar and Pestle

Source: Pharmaceutical Compounding and Dispensing (2008)

STEP 4: Preparation of Ointment (35 minutes)

• In preparation of ointments every official formula has got its procedures on how to carry out the

preparation, although the general procedures remain as mentioned on step 3 above.

Activity: Demonstration (25 minutes)

DIVIDE students in small manageable groups.

PREPARE equipment and materials needed for demonstration

POSITION students so that everyone can see and hear

REVIEW steps of preparing ointments with students

REFER students to the official formula of preparing calamine ointment PCx In

the Tanzania Pharmaceutical Handbook

DEMONSTRATE the procedure of preparing ointments according to the instruction under

the official formula in the Tanzania Pharmaceutical Handbook (Mitte 50g)

ALLOW one student from each group to do a return demonstration and let others comment

on it

CLARIFY and SUMMARIZE Using the content below

INFORM the students that “every student will practice in the skills laboratory under

supervision until is competent”

• Official formula given for calamine ointment PCx

Calamine, finely sifted……………………………………………………….15.0g

White soft paraffin……………………………………………………………85.0g

Mitte 50.0g for Anna Juma

Thus, amount of official formula = 100g

Total amount required = 50g

Amount of each ingredient (x) =?

FACTOR = required amount

Official amount

= 50gm

100g

= 0.5

Then, amount of each ingredient can be obtained as summarised in the table below:

Formula Official amount Factors Required amount

Calamine, finely sifted 15.0gm 0.5 7.5gm

White soft paraffin 85.0gm 42.5gm

Method of preparation

• Weigh 7.5g of calamine, finely sifted

• Transfer the weighed ( 7.5g) of calamine, finely sifted into a mortar

• Weigh 42.5g of white soft paraffin

• Add to the powders about two or three times their weight of white soft paraffin

• After each addition trituration should be done for 3 to 5 minutes

• Triturate until it is completely uniform

• Then transferred to suitable container, label and ready for dispensing to a patient.

STEP 5: Labeling of Prepared Ointment (20 minutes)

• Container should be labeled;

o “For External Uses Only” (red) and “Store at a Cool Place” when appropriate

o Strength of active ingredient should be given as % w/w, (or %v/v) or %w/v

o If diluted product should indicate,“Should Not be Used Later than Two Weeks After

Issue” unless otherwise stated

o If preserved, name and concentration should appear on the label

o Is sterile, should be labeled “Sterile”

Activity: Demonstration (25 minutes)

DIVIDE students in small manageable groups.

PREPARE equipment and materials needed for demonstration

POSITION students so that everyone can see and hear

REVIEW steps of writing a label

REFER students to the important things required to appear on the label.

DEMONSTRATE on how to write a good label

ALLOW one student from each group to do a return demonstration and let others comment

on it

CLARIFY and SUMMARIZE by using the content below

INFORM the students that “every student will practice in the skills laboratory under

supervision until is competent”

• Example of labels:

For External Use Only

CALAMINE OINTMENT PCx

100g

Apply to the affected parts every twelve hours after bath for seven days

The name of the dispenser and the name and address of the dispensing Institution

Preparation date

Discard after

Keep Out of Reach of Children

Keep it away from heat

STEP 6: Dispensing of Prepared Ointment into Suitable Containers and

Closure. (15 minutes)

Activity: Brainstorming (05 minutes)

Ask students to brainstorm on the following question:

• What are suitable containers and closure for ointments?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

Containers

• Well-closed containers

• Container should prevent evaporation

• Should prevent contamination of contents

• Should not release or absorb/adsorb anything from the contents=

• Flexible plastic tubes or

• Collapsible metal tubes

• Wide-mouth glass or plastic jars with plastic screw caps with impermeable liners or close fitting

slip-on lids

• Note:

• Check for reaction between container material and contents before making choice of containers

Figure 7.1: Ointment jars.

Source: Pharmaceutical Compounding and Dispensing (2008).

STEP 7: Key Points (5 minutes)

• Ointment is a viscous semisolid preparation, oily in nature used topically on a variety of body

surfaces, it is usually applied on the skin and the mucus membranes of the eye, vagina, anus, and

nose. An ointment may or may not be medicated.

• Ointment are used as: emollients to make skin more pliable, protective barriers, vehicles in

which to medications are incorporated. They may be readily applied to the skin with inunction

(smearing or rubbing)

• Basic Techniques for Preparation of ointment are weighing, measuring liquids, size reduction,

size separation (sieving) and mixing (Fusion or Trituration

STEP 8: Evaluation (5 minutes)

• What is ointment

• What are procedures for preparing ointments?

• What are suitable containers and closure for ointments?

References

Britain, R. P. S. o. G. (1994). The Pharmaceutical Codex (12 ed.). London: London Pharmaceutical

Press.

Winfield, J. A. R., I. Smith. (2009). Pharmaceutical Practice (4th ed.)British

Wolverton, SE. Comprehensive Dermatologic Drug Therapy. WB Saunders. 2001. pp 563-572.New

York

Singh Malik, D; Mital, N; Kaur, G (2016). "Topical drug delivery systems: a patent review". Expert

opinion on therapeutic patents. 26 (2): 213–28. Sudan

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011). Tanzania

Pharmaceutical Handbook (2nd ed.). Dar es salaam.

Session 8 Compounding of Pastes

Total Session Time: 120 Minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

 Define paste

 Describe procedures for preparing paste

 Prepare paste

 Label prepared paste

 Dispense prepared paste into suitable containers and closure

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

• Figure 8.1: Paste jars and tube

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

2 10 Minutes Presentation Definition of Paste

20 Minutes Presentation Procedures for Preparing Paste

Buzzing

45Minutes Presentation

4 Preparing Paste

Demonstration

20 Minutes Presentation

5 Labeling of Prepared Paste

10Minutes Presentation Dispensing of Prepared Paste into Suitable Containers

Brainstorming and Closure

7 05 Minutes Presentation Key Points

8 05 Minutes Presentation Evaluation

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Definition of Paste (10 minutes)

• Pastes are external semi-solid preparations containing large proportions (20% -60%) of solids

finely dispersed in the basis

• Pastes are like ointments but contain more solid materials and are stiffer

• Pastes are basically ointments into which a high % of insoluble solid has been added

• There are two types of paste:

o Fatty pastes e.g.: Lassar's paste

o Non greasy pastes e g: Bassorin paste

• Examples of pastes

o Coal tar paste P.CX (astringent, antipruritic)

o Compound zinc paste P.CX (astringent)

o Zinc and Salicylic acid Paste P.CX (Lassar‟s paste) astringent

• Characteristics

o Contain more solids than ointments

o Are stiffer than ointments

o Are less greasy than ointments

o Cause less maceration of the skin

o Are less occlusive than ointment

 This is because of high porosity caused by high powder content

o Are more absorbent to exudate weeping lesions

o Pastes are less penetrating and less macerating and less heating than ointment

o Like ointments; paste forms an unbroken relatively water – impermeable film

o Unlike ointments; film formed by pastes is opaque, thus can be used as an effective sun block

accordingly.

STEP 3: Describe Procedures for Preparing Pastes (20 minutes)

Activity: Buzzing (10 minutes)

Ask students to brainstorm on the following question:

• What are procedures for preparing pastes?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Preparation more less like ointments

o e.g. Compound Zinc Paste P.CX (Syn Zinc Paste)

o Zinc oxide, finely sifted ……………….. 25.0g

o Starch, finely sifted……………………….25.0g

o White soft paraffin……………………….50.0g

o The powders are triturated with the melted soft paraffin

STEP 4: Preparation of Pastes (45 minutes)

Activity: Demonstration (45 minutes)

DIVIDE students in small manageable groups.

PREPARE equipment and materials needed for demonstration

POSITION students so that everyone can see and hear

REVIEW steps of preparing pastes with students

REFER students to the official formula of preparing compound zinc paste PCx In the

Tanzania Pharmaceutical Handbook

DEMONSTRATE the procedure of preparing ointments according to the instruction under the

official formula in the Tanzania Pharmaceutical Handbook (Mitte 50g)

ALLOW one student from each group to do a return demonstration and let others comment on it

CLARIFY and SUMMARIZE Using the content below

INFORM the students that “every student will practice in the skills laboratory under supervision

until is competent”

• Official formula given for compound zinc paste PCx

Zinc oxide, finely sifted………………………………………………………..25.0g

Starch, finely sifted……………………………………………………………..25.0g

White soft paraffin………………………………………………………………50.0g

Mitte 50.0g for Alex Shabani

Thus, amount of official formula = 100g

Total amount required = 50g

Amount of each ingredient (x) =?

FACTOR = required amount

Official amount

= 50gm = 0.5

100gm

Then, amount of each ingredient can be obtain as summarised in the table below:

Formula Official amount Factor Required amount

Zinc oxide, finely 25.0gm 0.5 12.5gm

sifted

Starch, finely sifted 25.0gm 12.5gm

White soft paraffin 50.0gm 25.0gm

Method of preparation

• Weigh 12.5g of Zinc oxide, finely sifted and 12.5g Starch, finely sifted

• Transfer the weighed ( 12.5g) of Zinc oxide, finely sifted and Starch, finely sifted into a mortar

• Weigh 25.0g of white soft paraffin

• Add to the powders about two or three times their weight of melted white soft paraffin

• After each addition trituration should be done for 3 to 5 minutes

• Triturate until it is completely uniform

• Then transferred to suitable container, label and ready for dispensing to a patient.

STEP 5: Labeling of Prepared Paste (20 minutes)

• Labeling

o As for ointments

Activity: Demonstration (10 minutes)

DIVIDE students in small manageable groups.

PREPARE equipment and materials needed for demonstration

POSITION students so that everyone can see and hear

REVIEW steps of writing a label

REFER students to the important things required to appear on the label.

DEMONSTRATE on how to write a good label

ALLOW one student from each group to do a return demonstration and let others comment

on it

CLARIFY and SUMMARIZE by using the content below

INFORM the students that “every student will practice in the skills laboratory under

supervision until is competent”

• Example of labels:

For External Use Only

ZINC AND SALICYLIC ACID PASTE PCx

100g

Spread paste on white lint and place on to the affected area every twenty four

hours for five days.

The name of the dispenser and the name and address of the dispensing Institution

Preparation date

Expiry date

Keep Out of Reach of Children

Keep away from heat

STEP 6: Dispensing of Prepared pastes into Suitable Containers and

Closure. (10 Minutes)

Activity: Brainstorming (05 minutes)

Ask students to brainstorm on the following question:

• What are suitable containers and closure for pastes?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Containers

o As for ointments

o Pastes tubes of metal or plastic or in wide-mouthed jars of glass or plastic

Figure 8.1: Paste jars and tube

Source: Pharmaceutical Compounding and Dispensing (2008).

STEP 6: Key Points (5 minutes)

• Pastes are external semi-solid preparations containing large proportions (20% -60%) of solids

finely dispersed in the basis

• Procedures for preparing pastes include; weighing, measuring liquids, size reduction, size

separation (sieving) and mixing (Fusion or Trituration),

• Suitable containers and closure for pastes are: flexible plastic tubes or collapsible metal tubes,

wide-mouth glass or plastic jars with plastic screw caps with impermeable liners or close fitting

slip-on lids

STEP 8: Evaluation (5 minutes)

• What are pastes?

• What are procedures for preparing pastes?

• What are suitable containers and closure for pastes?

References

Britain, R. P. S. o. G. (1994). The Pharmaceutical Codex (12 ed.). London: London Pharmaceutical

Press.

Winfield, J. A. R., I. Smith. (2009). Pharmaceutical Practice (4th ed.)British

Singh Malik, D; Mital, N; Kaur, G (2016). "Topical drug delivery systems: a patent

review". Expert opinion on therapeutic patents. 26 (2): 213–28. Sudan

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011).

Tanzania Pharmaceutical Handbook (2nd ed.). Dar es salaam.

Session 9: Compounding of Creams

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

 Define creams

 Describe procedures for preparing creams

 Prepare creams

 Label prepared cream

 Dispense prepared cream into suitable containers and closure

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

• Figure 9.1: Cream jars and tube

SESSION OVERVIEW

Step Time Activity/Method Content

1 05 Minutes Presentation Introduction, Learning Tasks

15 Minutes Presentation Definition of creams

Buzzing

3 15 Minutes Presentation Procedures for preparing creams

Presentation

4 Preparing of Creams

30 Minutes Demonstration

Presentation

5 Labeling of prepared creams

30 Minutes Demonstration

15 Minutes Presentation Dispensing of prepared creams into suitable

Brainstorming containers and closure

7 05 Minutes Presentation Key Points

8 05 Minutes Presentation Evaluation

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Definition of Creams (15 minutes)

Activity: Buzzing (05 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What are creams?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Creams are semi-solid emulsions intended for application to the skin or mucous membrane, they

are viscous semisolid emulsion system with opaque appearance

• Usually they are of two types, namely:

o Aqueous creams, i.e. oil-in-water emulsions (O/W). This creams contain oil-in-water

emulsifying agent

o Oily creams, i.e. water-in-oil emulsions (W/O). This cream contain water-in-oil emulsifying

agent.

• Aqueous creams are relatively non-greasy and are most useful as water-washable bases whereas

oily creams are emollient and cleansing.

• Patients often prefer a w/o cream to an ointment because the cream spreads more readily, is less

greasy and the evaporating water soothes the inflamed tissue.

• O/w creams („vanishing‟ creams) rub into the skin; the continuous phase evaporates and increases

the concentration of a water-soluble drug in the adhering film.

• Consistency and rheological characters depend on weather the cream is w/o or o/w.

• Creams intended for application to large open wounds should be sterile.

STEP 3: Procedures for Preparing Creams (15 minutes)

• Emulsified creams are prepared by heating the components of the oily phase including the

emulgent until molten and then cooling to 60°C.

• The components of the aqueous phase are mixed in a separate vessel and also heated at 60°C.

• The aqueous phase is then added to the oily phase at the same temperature, this is very important

and the thermometer should be used.

• The resulting emulsion should be stirred until cool.

• Rapid cooling may result in separation of high melting point components and excessive aeration

caused by vigorous stirring may also lead to a granular product.

• If necessary the product may be homogenized after cooling.

• Dilution of creams

o Should be done under hygienic conditions

o Stability and bacteriocidal properties of original cream should NOT be reduced on dilution

o The diluent should be compatible with ingredients and the whole original preparation

o Dilution may alter extent of release of medicament from creams

o Information on suitability of diluent should be available, otherwise DO NOT DILUTE

• Preservation & hygiene during preparation

o Creams can support growth of micro-organisms, hence most need preservatives

o Accidental contamination will almost certainly occur during bench scale manufacture, but

good technique can keep this to a minimum

o All apparatus and final containers should be thoroughly cleansed before use and purified

water should be used in the preparation of products

STEP 4: Preparing of Creams (30 minutes)

Activity: Demonstration (15 minutes)

DIVIDE students in small manageable groups.

PREPARE equipment and materials needed for demonstration

POSITION students so that everyone can see and hear

REVIEW steps of preparing pastes with students

REFER students to the official formula of preparing aqueous calamine cream

PCx In the Tanzania Pharmaceutical Handbook

DEMONSTRATE the procedure of preparing cream according to the instruction under the

official formula in the Tanzania Pharmaceutical Handbook (Mitte 50g)

ALLOW one student from each group to do a return demonstration and let others comment

on it

CLARIFY and SUMMARIZE Using the content below

INFORM the students that “every student will practice in the skills laboratory under

supervision until is competent”

• Official formula given for aqueous calamine cream PCx

Calamine……………………………………………………………… 4.0g

Zinc oxide……………………………………………………… 3.0.0g

Emulsifying wax………………………………………………… 6.0g

Arachis oil (0.86g/mL)…………………………………………….. 30.0g

Purified water, freshly boiled and cooled ………………………… 50.0g

Mitte 50.0g for Okeyo Odhiambo

o Thus, amount of official formula = 100g

o Total amount required = 50g

o Amount of each ingredient (x) =?

o FACTOR= Required amount

Official amount

= 50gm

100gm

= 0.5

Then, amount of each ingredient can be obtain as summarised in the table below:

Formula Official amount Factor Required amount

Calamine 4.0gm 2.0g

Zinc oxide 3.0gm 1.5g

Emulsifying wax 6.0gm 0.5 3.0g

Arachis oil (0.86g/mL) 30.0gm 15.0g

Purified water, freshly 57.0gm 28.5g

boiled and cooled

Method of preparation

• Melt oily phase (heat up to 75oC, and cool to 60oC)

• Prepare aqueous phase and heat to 60oC

• Add aqueous phase to oily phase with slow but constant agitation until cold

• Incorporate insoluble medicinal ingredient

• Then transferred to suitable container, label and ready for dispensing to a patient.

STEP 5: Labeling of Prepared Creams (30 minutes)

• The preparation should be labelled “For External Use Only” in red ink and bear the instructions

that it should be stored in a cool place.

• The strength of active ingredients must be stated as percentage by weight or by volume.

• For diluted creams, the label should state that the product should not be used after two weeks

from the date it was dispensed unless otherwise stated.

• The date of dispensing (preparation date)

• Instruction for use.

• The expiry date, where applicable and/ or manufacturing date

• Storage condition

• The name of the dispenser (initial)

• The name and address of the dispensing institution.

Activity: Demonstration (15 minutes)

DIVIDE students in small manageable groups.

PREPARE equipment and materials needed for demonstration

POSITION students so that everyone can see and hear

REVIEW steps of writing a label

REFER students to the important things required to appear on the label.

DEMONSTRATE on how to write a good label

ALLOW one student from each group to do a return demonstration and let others comment

on it

CLARIFY and SUMMARIZE by using the content below

INFORM the students that “every student will practice in the skills laboratory under

supervision until is competent”

Example of labels:

For External Use Only

AQUEOUS CALAMINE CREAM PCx

100g

MR.AMON JUMA

Apply to the affected parts every twenty four hours for seven days

The name of the dispenser and the name and address of the dispensing Institution

Preparation date

Discard after

Keep Out of Reach of Children

Keep away from heat

STEP 6: Dispensing of Prepared Creams into Suitable Containers and

Closure. (15 minutes)

Activity: Brainstorming (05 minutes)

Ask students to brainstorm on the following question:

• What are suitable containers and closure for creams?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Creams should be dispensed in well-closed containers to prevent evaporation of the aqueous phase.

• Wide-mouthed squat jars may be used for creams where the risk of contamination may be minimal

but the mouth of the jar should be covered with a disc of greaseproof paper.

• Collapsible metal or flexible plastic tubes are to be preferred since these reduce the risk of

contamination during use, most creams are packed in tubes.

Figure 9.1: Cream jars and tube

Source: Pharmaceutical Compounding and Dispensing (2008).

STEP 7: Key Points (5 minutes)

• Creams are semi-solid emulsions intended for application to the skin or mucous membrane, they

are viscous semisolid emulsion system with opaque appearance

• Usually they are of two types, namely: aqueous creams, i.e. oil-in-water emulsions this creams

contain oil-in-water emulsifying agent and oily creams, i.e. water-in-oil emulsions, this creams

contain water-in-oil emulsifying agent.

• Suitable containers and closure for creams are: Flexible plastic tubes or collapsible metal tubes

and wide-mouth glass or plastic jars with plastic screw caps with impermeable liners or close

fitting slip-on lids

STEP 8: Evaluation (5 minutes)

• What are creams?

• What are procedures for preparing creams?

• What are suitable containers and closure for creams?

References

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011).

Tanzania Pharmaceutical Handbook (2nd ed.). Dar es salaam.

Britain, R. P. S. o. G. (1994). The Pharmaceutical Codex (12 ed.). London: London Pharmaceutical

Press.

Winfield, J. A. R., I. Smith. (2009). Pharmaceutical Practice (4th ed.)British

Wolverton, SE. Comprehensive Dermatologic Drug Therapy. WB Saunders. 2001. pp 563-572.New

York

Singh Malik, D; Mital, N; Kaur, G (2016). "Topical drug delivery systems: a patent review". Expert

opinion on therapeutic patents. 26 (2): 213–28. Sudan

Session 10: Compounding of Gels/ Jellies

Total Session Time: 120 Minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

 Give overview of gels

 Describe procedures for preparing gels

 Prepare gels

 Label prepared gels

 Dispense prepared gels into suitable containers and closure

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

• Figure 10.1: Gels jars and tube

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

Presentation

25 Minutes Buzzing Introduction to Gels

3 10 Minutes Presentation Procedures for Preparing Gels

Presentation

4 Preparing Gels

35 Minutes Demonstration

Presentation

25 Minutes Demonstration Labeling of Prepared Gels

Presentation Dispensing of Prepared Gels into Suitable Containers

10 Minutes Brainstorming and Closure

7 05 Minutes Presentation Key Points

8 05 Minutes Presentation Evaluation

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Introduction to Gels (25 minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What are Gels?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Gels are transparent (or translucent) semi-solid or solid preparations of either suspensions made

up of small inorganic particles or large organic molecules interpenetrated by a liquid

• Are semisolid systems consisting of dispersion of small or large molecules in an aqueous liquid

vehicle rendered jelly-like through addition of a gelling agent

• Movement of dispersing system is restricted by interlacing network of particles or solvated

macromolecules of dispersed phase

• Gels are made using substances (called gelling agents) that undergo a high degree of cross-

linking or association when hydrated and dispersed in the dispersing medium or when dissolved

in the dispersing medium

• Cross-linking or association of dispersed phase alters the viscosity of the dispersing medium

• Hence the movement of dispersing medium is restricted by the dispersed phase

• Two-phase System Gel

o Is when the gel contains a network of small discrete particles

• One or Single-phase System Gel

o When gels appear to have no discrete particles,

o Macromolecules are uniformly distributed throughout the liquid, usually organics

o No apparent boundaries between dispersed macromolecules and the liquid

o Two-phase system gels are thixotropic

Gel mass consists of floccules of small distinct particles

Usually involve inorganics

Semisolid on standing but liquefy on shaking

If the particles in the two-phase systems are large

• The gel is called a Magma or Milk

Composition of gels is:

o Gelling agents

o Water

o Co-solvents

o Preservatives

o Stabilizers

• One-phase gels are made from synthetic or natural organic macromolecules distributed uniformly

throughout a liquid without any boundary between dispersed and dispersing phases (e.g.

tragacanth, cellulose, methylcellulose)

• If made from natural gum, single-phase gels are called Mucilages

• Some Gelling Agents

o Acacia, tragacanth, Methylcellulose,

o Alginic acid, Bentonite, Carbopol®,

o Carboxymethylcellulose (CMC),

o Gelatin, Hydroxypropyl cellulose,

o Magnesium Aluminium Silicate (Veegum®) etc

• Characteristic Properties of gels are:often non-greasy, smooth, elegant, produce cooling effect on

application and easily washable from skin

STEP 3: Procedures for Preparing Gels (10 minutes)

• Specific method depends on gelling agent

o e.g. gelatin gels

o By dispersing gelatin in hot water followed by cooling OR

o By wetting gelatin with organic liquid e.g. Propylene glycol, followed by addition of hot water

and cooling

• Example of a gel formulation:

• Methylcellulose and Carbomer Gel Base

o Methylcellulose, 4000cps 1.0%

o Carbomer 934 0.35%

o 1N Sodium Hydroxide Solution qs to pH 7

o Propylene glycol 16.7%

o Methyl paraben 0.015%

o Purified water, qs 100

o Disperse the methylcellulose in a portion of hot (80-90°C) water

o Cool to room temperature, and disperse the Carbomer 934 in the gel using a bladed stirrer.

o Adjust the pH of the dispersion to 7.0 by adding sufficient 1N Sodium hydroxide solution.

o Dissolve the methylparaben in the propylene glycol. Mix the methylcellulose, Carbopol 934

and propylene glycol fractions using caution to avoid incorporating air.

STEP 4: Preparing of gels (35 minutes)

Activity: Demonstration (45 minutes)

DIVIDE students in small manageable groups.

PREPARE equipment and materials needed for demonstration

POSITION students so that everyone can see and hear

REVIEW steps of preparing pastes with students

REFER students to the official formula of preparing Ichthammol gel IP In the

Tanzania Pharmaceutical Handbook

DEMONSTRATE the procedure of preparing ointments according to the instruction under

the official formula in the Tanzania Pharmaceutical Handbook (Mitte 50g)

ALLOW one student from each group to do a return demonstration and let others comment

on it

CLARIFY and SUMMARIZE Using the content below

INFORM the students that “every student will practice in the skills laboratory under

supervision until is competent”

• Official formula given for Ichthammol gel PCx

Ichthammol……………………………………………………….. 1.0g

Tragacanth, in powder……………………………………………… 2.5g

Alcohol 90%……………………………………………………………… 5.0g

Glycerin……………………………………………………………… 1.0g

Purified water q.s………………………………………………………… 50.0g

Mitte 50.0g for Allen Mbogo

• Thus, amount of official formula = 100g

• Total amount required = 50g

• Amount of each ingredient (x) =?

• FACTOR= Required amount

Official amount

= 50g

100g

= 0.5

Then, amount of each ingredient can be obtain as summarised in the table below:

Formula Official amount Factors Required amount

Ichthammol 1.0g 0.5g

Tragacanth, in powder 2.5g 0.5 1.25g

Alcohol 90% 5.0g 2.5g

Glycerol 1.0g 0.5g

Purified water q.s 50.0g 25g

Procedure:

• Prepare Ichthammol solution:

o According to solubility,

o 1g Ichthammol 10ml water

• Formula for Ichthammol solution:

o Ichthammol 1.0g

o Glycerol 1.0g

o Water 10ml

Weigh empty beaker (preferably plastic) and weigh1.0g of Ichthammol and 1.0g of glycerol directly

into beaker. Add about 10ml of water then stir until obtaining solution.

• Prepare mucilage:

o Calculate amount of water

o Final weight of jelly – other ingredients.

-50g – (1.0g+2.5g+5.0g+1.0g)

Ichthammol Tragacanth Alcohol Glycerol

(Approximate Conversion)

=50g – 9.5g =40.5g – 40g =40ml water used in preparation

10ml water has been used for Ichthammol solution

40ml – 10ml=30ml: Amount of water can be used for mucilage.

• Formula for mucilage

o Tragacanth 2.5gm

o Alcohol (90%) 5.0mL

o Water 30mL

• Weigh2.5g of Tragacanth and measure 5.0ml of alcoholand

30ml of water.

o Place alcohol first in mortar and add Tragacanth onto alcohol then disperses by pestle.

o After obtaining uniform dispersion, add water as quickly as possible at once then mix well.

NB: Alcohol should be placed first otherwise may lead lump formation

• Combine:

o Add Ichthammol solution into the mucilage in portion triturate frequently scraping off the

material from the side soft hemortar and the pest leuntil obtaining completely uniform

mixture

• Adjust final weight:

o Weigh the empty dispensing container, then transfer jellies into the container.

o Make the required weight by rinsing the mortar and pestle with a small amount of water.

o When the weight is made up, mix the contents well by stirring rod

o Make sure that the product is uniform

STEP 5: Labeling of Prepared Gels (25 minutes)

• As for other external semisolids or otherwise stated

Activity: Demonstration (10 minutes)

DIVIDE students in small manageable groups.

PREPARE equipment and materials needed for demonstration

POSITION students so that everyone can see and hear

REVIEW steps of writing a label

REFER students to the important things required to appear on the label.

DEMONSTRATE on how to write a good label

ALLOW one student from each group to do a return demonstration and let others comment

on it

CLARIFY and SUMMARIZE by using the content below

INFORM the students that “every student will practice in the skills laboratory under

supervision until is competent”

• Example of labels:

For External Use Only

ICHTHAMMOL GEL IP

50g

Spread the medicine in a thin layer and then apply to the affected part every twelve

hours for seven days

The name of the dispenser and the name and address of the dispensing Institution

Preparation date

Expiry date

Keep Out of Reach of Children

Keep away from heat

STEP 6: Dispensing of Prepared Gels into Suitable Containers and

Closure. (10 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

• What are suitable containers and closure for gels?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Containers containing gels should be well filled to minimise evaporation of water

• Well closed and stored in a cool place to prevent drying out

• Collapsible tubes should be used for packing the sterile products such as catheter

Figure 10.1: Gels jars and tube

Source: Pharmaceutical Compounding and Dispensing (2008).

STEP 7: Key Points (5 minutes)

• Gels are transparent (or translucent) semi-solid or solid preparations of either suspensions made

up of small inorganic particles or large organic molecules interpenetrated by a liquid

• Procedures for preparing gels include: by dispersing gelatin in hot water followed by cooling OR

by wetting gelatin with organic liquid e.g. Propylene glycol, followed by addition of hot water

and cooling

• Suitable containers and closure for creams are: containers containing gels should be well filled to

minimise evaporation of water, well closed and stored in a cool place to prevent drying out and

collapsible tubes should be used for packing the sterile products such as catheter

STEP 8: Evaluation (5 minutes)

• What are gels?

• What are procedures for preparing gels?

• What are suitable containers and closure for gels?

References

Britain, R. P. S. o. G. (1994). The Pharmaceutical Codex (12 ed.). London: London Pharmaceutical

Press.

Winfield, J. A. R., I. Smith. (2009). Pharmaceutical Practice (4th ed.)British

Wolverton, SE. Comprehensive Dermatologic Drug Therapy. WB Saunders. 2001. pp 563-572.New

York

Singh Malik, D; Mital, N; Kaur, G (2016). "Topical drug delivery systems: a patent review". Expert

opinion on therapeutic patents. 26 (2): 213–28. Sudan

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011). Tanzania

Pharmaceutical Handbook (2nd ed.). Dar es salaam.

Session 11: Introduction to Isotonicity

Total Session Time: 60 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Define terms used in isotonicity

• Explain the importance of isotonic solution.

• Explain effects of administering paratonic solutions

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Step Time Activity/Method Content

1 05 Minutes Presentation Introduction, Learning Tasks

Presentation Definition of Terms Used in Isotonicity and

2 15 Minutes

Brainstorming Electrolytes.

15 Minutes Presentation Importance of isotonic solution.

Small group discussion

4 15 Minutes Presentation Effects of administering paratonic solutions

5 05 Minutes Presentation Key Points

05 Minutes Presentation

6 Evaluation

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Definition of Terms used in Isotonicity and Electrolytes (15 minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What is isotonicity?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Body fluids e.g. blood plasma have certain quantity of dissolved substances e.g. salts that

determine power of the blood called osmotic pressure.

• Osmotic pressure is the pressure created by solvent molecules moving from a low concentrated

solution to higher concentrated solution through a semi-permeable membrane, a semi-permeable

membrane allow only the solvent molecules to pass.

• The characteristics of a solution is determined by the number of dissolved substances in it,

aqueous solutions which exert the same osmotic pressure as blood plasma are said to be isotonic

with plasma. This is equivalent to 0.9%w/v sodium chloride injection (Normal saline)

• An isotonic solution is a solution in which body cells can be bathed without a net flow of water

across a semipermeable membrane. E.g. 0.9% normal saline (NS).

• Osmolality

o A unit of measure of osmotic pressure.

o Blood has 300 mOsmol per liter. (MiliOsmolality)

o Both Normal Saline and Dextrose 5% solutions have a similar osmolarity.

• Solutions, which exert a different osmotic pressure as blood plasma, are said to be paratonic with

plasma. (i.e. solutions with hypotonic or hypertonic osmotic pressure)

• Those solutions with a lower osmotic pressure than blood plasma are said to be hypotonic

solutions and a solution of less than normal tonicity is hypotonic, which has fewer numbers of

dissolved solutes than blood cells. E.g. 0.45% Normal Saline.

• Solutions with a higher osmotic pressure than blood plasma are said to be hypertonic solutions, a

hypertonic solution has more number of dissolved solutes than the blood cells themselves. E.g.

50% Dextrose or 3% Sodium chloride.

• Aqueous solutions intended to contact with body fluid should preferably be made isotonic with

speci※c bodily ‼uid in order to minimize any possible adverse effects.

• Tonicity is generally classified in three types:

o Hypertonicity

o Hypo tonicity

o Isotonicity

• Hypertonic, isotonic and hypotonic solutions are defined in reference to a cell membrane by

comparing the tonicity of the solution with the tonicity within the cell.

• For a solution to be termed isotonic (equal tone) it must have the same osmotic pressure as a

speci※c bodily ‼uid. The easiest way to calculate the osmotic pressure

of a solution is to utilize the more easily measured property of the freezing point depression, as

they are proportional to one another.

• In pharmacy, isotonicity calculations are most often performed for parenteral and ophthalmic

solutions, which must have a freezing point depression of 0.520C for them to be isotonic with

blood plasma and tears. Therefore a solution is considered to be isotonic if it has a freezing point

of -0.520C

• Electrolytes are substances containing free ions, thus rendering the substance electrically

conductive

• Electrolyte preparations are used in the treatment of disturbances of electrolyte and fluid balance

in the body. In clinical practice, they are provided in the form of oral solutions, and syrup as dry

granules intended to be dissolved in water or juice to make an oral solution and when necessary as

intravenous infusions

STEP 3: Importance of Isotonicity (15 minutes)

Activity: Small Group Discussion ( 10 minutes)

DIVIDE students into small manageable groups

ASK students to discuss on the following question

• What is the importance of isotonicity?

REFER Students to Tanzania Pharmaceutical Handbook pg. 33-50

ALLOW students to discuss for 10 minutes

ALLOW few groups to present and the rest to add points not mentioned

CLARIFY and SUMMARIZE by using the contents below

• It is important for a solution to be isotonic with a bodily ‼uid to prevent irritation and cell

damage, and to maximize drug eﬃcacy. Its neutrality is not affecting the osmotic pressure of a

cell

• This state allows for the free movement of water across the membrane without changing the

concentration of solutes on either side.

• Isotonic solutions are used in Oral Rehydration Therapy (ORT), which is a treatment for

dehydration associated with gastroenteritis. ORT replenishes the body's lost electrolytes and

promotes the uptake of glucose and fluid by the intestinal epithelial cells.

• Isotonic solutions given intravenously in case of severe dehydration and is used in the treatment

of hypernatremia (a condition in which serum concentration of sodium is high) in individuals who

have impaired water excretion, eg 0.9% NaCl solution

• It can be used as a medium for intravenous administration of drugs like propofol, which are not

absorbed well by the intestinal lining.

• They are used in the treatment of conditions like hypovolemia (a condition in which blood

volume is lowered either due to injury or other reasons) and acidosis (a condition in which the

acidity of the blood increases), eg Lactated Ringer's solution and Hartmann's solution

Isotonic solution used as mediums for dissolving drugs that are used for nebulization

(administration of drugs in the form of aerosol), such as ipratropium or salbutamol, eg:

0.9% NaCl or 0.14% H2CO3 solutions

• It can be used as an aqueous medium for making many medicines that are administered through

the ocular routes such as rinse, eye drops, steroids, antihistamines, antibiotics, etc

Figure 11. 1.: Importance of Isotonic solution

Source: http://www.imedpub.com/journal-pharmacy-practice-education/ 2018

STEP 4: Effects of Administering Paratonic Solutions (15 minutes)

Intravenous injections

• Effects of hypotonic solutions on blood-cells:

o When hypotonic solution is injected into the blood stream, blood cells swell rapidly and burst,

i.e. the solution cause haemolysis of blood cells particularly if the solution is very hypotonic

or a large volume of less hypotonicity.

o This damage is irreversible and dangerous if a large number of cells are involved.

• Effects of hypertonic solutions on blood-cells

o When hypertonic solution is injected into the blood stream, water passes outwards from blood

cells and they shrink, becoming crenate (curved/bent), blood cells returns to normal shape

when osmotic pressure becomes normal.

o Therefore, grossly hypertonic solutions may be administered without damage to blood cells,

thus injections, which are hypertonic, are slowly injected intravenously to ensure rapid

dilution in the blood stream and minimal crenulations of the blood cells.

Figure 11.2: Types of tonicity solutions

Hypotonic Isotonic Hypertonic

NaCl 0.2% NaCl 0.9% NaCl 2%

solute

› solute solute

= solute solute

‹ solute

Inside outside Inside outside Inside outside

Swelling Equilibrium shrinkage

Source: http://www.imedpub.com/journal-pharmacy-practice-education/ 2018

Figure 11.3: Schematic representation of erythrocyte behavior in tonicity solutions

Source: http://www.imedpub.com/journal-pharmacy-practice-education/ 2018

Figure 11.4: Schematic representation of erythrocyte behavior in tonicity solutions

Source: http://www.imedpub.com/journal-pharmacy-practice-education/ 2018

STEP 5: Key Points (5 minutes)

• Body fluids e.g. blood plasma have certain quantity of dissolved substances e.g. salts that

determine power of the blood called osmotic pressure.

• Osmotic pressure is the pressure created by solvent molecules moving from a low concentrated

solution to higher concentrated solution through a semi-permeable membrane, a semi-permeable

membrane allows only the solvent molecules to pass.

• Tonicity is a measure of the osmotic pressure of two solutions separated by a semi-permeable

membrane, it is important for a solution to be isotonic with a bodily ‼uid to prevent irritation and

cell damage, and to maximize drug eﬃcacy.

STEP 6: Evaluation (5 minutes)

• What is osmotic pressure

• What is the importance of isotonic solutions

References

Patel H, Parikh VP (2017) an Overview of Osmotic Drug Delivery System: an update review.

International Journal of Bioassays 6(7): 5426-5436.

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011). Tanzania

Pharmaceutical Handbook (2nd ed.). Dar es salaam:

A. J. Winfield, J. A. R., I. Smith. (2009). Pharmaceutical Practice (4th ed.) New York

Britain, R. P. S. o. G. (1994). The Pharmaceutical Codex (12 ed.). London: London Pharmaceutical

Press.

Doemling DP (1998) Isotonic vs Isosmotic Solutions: A Clarification of Terms. JAMA,203(3): 232-

233.

Sareen R, Jain N, Kumar D (2012) An insight to osmotic drug delivery. Curr. Drug Deliv. 9(3): 285-

296.India

Session 12: Determination of Isotonicity by Freezing Point

Method

Total Session Time: 120 minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Define freezing point depression

• Determine the isotonicity by freezing point depression

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

2 45 Minutes Presentation Introduction to Freezing Point Depression

Presentation Determining the Isotonicity by freezing Point

3 60 Minutes Small Group Depression

Discussion

4 05 Minutes Presentation Key Points

5 05 Minutes Presentation Evaluation

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Freezing Point Depression (45 minutes)

• The freezing point of body fluid is at – 0.520C.

• Any solution freezing at – 0.520C will have the same osmotic pressure as body fluids

• Hypotonic solution will have a higher freezing-point and consequently need the addition of

adjusting substance to reach a freezing point of – 0.520C

• The amount of adjusting substance which is often sodium chloride, is calculated as shown in the

following examples.

o Solution A freezes at – 0.390C. How much sodium has to be added to obtain an isotonic

solution?

o The adjusting substance sodium chloride has to decrease the freezing point by 0.52 – 0.39 =

0.130C

o A 1 % w/v sodium chloride solution freezes at – 0.5760C; so the amount needed is found by

the proportion:

o 1 == x x == 1 x 0.13 == 0.2%w/v

0.576 0.13 0.576

• Therefore, solution A will need the addition of 0.2%w/v sodium chloride in order to become

isotonic with body fluids; e.g. 50mL of this solution require 0.1g sodium chloride.

• From the above used proportion, the following equation has been derived:

o W == 0.52 – a

o Where:

 w== concentration %w/v of adjusting substance in the final solution

 a == freezing point of unadjusted solution

 b==freezing point of a 1%w/v solution of adjusting substance

• The freezing points of 1%w/v aqueous solution of various substances are obtain from the table

below; “a „ is calculated by multiplying the freezing depression of a 1%w/v solution by the

concentration of unadjusted solution expressed as %w/v

• Example:

o Adjust 1000mL of a 2%w/v solution of anhydrous dextrose isotonic with body fluids;

adjusting substance is sodium chloride

 Freezing point of 1%w/v anhydrous dextrose solution : – 0.1010C

 Freezing point of unadjusted solution: – 0.101 x 2 == – 0 .2020C

 Freezing point of 1%w/v sodium chloride solution = -0.5760C

 The last two values are substituting “ a “ and “b” in the formula

o W = 0.52 – 0.202 = 0.318 = 0.55%w/v

0.576 0.576

o Therefore, a 2%w/v anhydrous dextrose solution requires the addition of 0.55%w/v

sodium chloride in order to become isotonic with blood serum and tears; for 1000mL

solution 5.5g are needed

STEP 3: Determining the Isotonicity by Freezing Point Depression (60 minutes)

To determine amount of ingredients required to make isotonic solution

Activity: Small Group Discussion ( 30 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

1. Render the following solution iso – osmotic with blood and tears

Ephedrine hydrochloride…………………………0.1g

Chlorbutol…………………………………………0.1g

Water for preparation……………………….to 20mL

Adjusting substance is sodium chloride

REFER Students to Pharmaceutical Calculation. 13th Edition by HOWARD C.

ANSEL: Chapter 11, For reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

• The freezing point depression of 1%w/v solution is obtained from the table below.

• First the concentrations %w/v must be calculated for ephedrine hydrochloride and Chlorbutol by

proportion:

0.1 = xx =0.1 x100 x = 0.5%w/v

20 100 20

• A 0.5%w/v solution of ephedrine hydrochloride has a freezing point depression of 0.165 x 0.5 =

0.08250C

• A 0.5%w/v solution for Chlorbutol has a freezing point depression of 0.14 x 0.5 =0.070C

• Now the equation can be used:

W = 0.52 – 0.1525 ==0.3675 = 0.638%w/v =0.64%w/v

0.576 0.576

• Therefore, the unadjusted solution needs the addition of 0.64%w/v sodium chloride. The actual

amount for 20mL solution is found by simple proportion

0.638 = x x = 0.638 x 20 =0.1276gm of sodium chloride

100 20 100

• So the formula for the adjusted solution becomes:

Ephedrine hydrochloride…………………………0.1g

Chlorbutol………………………………………..0.1g

Sodium chloride………………………………….0.13g

Water for preparation……………………….to 20mL

STEP 4: Key Points (5 minutes)

• Freezing-point depression is the decrease of the freezing point of a solvent on addition of a non-

volatile solute

• The formula for determining the Isotonicity by freezing point depression is

w= 0.52 – a

STEP 5: Evaluation (5 minutes)

• What is freezing point depression in determining isotonicity?

• What is the formula for determining isotonicity by freezing point depression?

STEP 6: Take Home Assignment (15 minutes)

Activity: Take home Assignment (15 minutes)

ASK each individual student to do the following assignment

• Calculate the strength of sodium chloride solution which is iso – osmotic with blood

serum and tears

ALLOCATE time for students to do the assignment and submit

REFER students to recommended references

References

Aulton, M. E., & Taylor, K. (2013). Aulton's pharmaceutics : the design and manufacture of

medicines (4th ed.). Edinburgh: Churchill Livingstone/Elsevier.

Pharmaceutical Society of Great Britain., & Pharmaceutical Society of Great Britain. Department of

Pharmaceutical Sciences. (1994). The Pharmaceutical Podex, Principles and Practice of

Pharmaceutics (W. Lund Ed. 12th ed.). London,: Pharmaceutical P.

Senya, S. S., Mwasha, C. Y. S., Muyinga, A. M., Amiri, R. I., & Mauga, E. A. S. K. (2011).

Tanzania Pharmaceutical Handbook (2nd ed.). Dar es salaam: School of Pharmaceutical

Sciences, Institute of Allied Health Sciences, Muhimbili University of Health and Allied

Health Sciences.

Remington, J. P. (2005). Remington, the science and practice of pharmacy (T. David Ed. 21st ed.).

Easton, Pa. London, UK: Mack Pub. Co. Pharmaceutical Press.

Ansel, H. C., Stockton, S. J., & Bradley, W. T. (2017). Pharmaceutical calculations. Philadelphia:

Wolters Kluwer.

Session 13: Determination of Isotonicity by Sodium Chloride

Equivalent Method

Total Session Time: 120 minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give overview of sodium chloride equivalent method

• Determine the isotonicity by sodium chloride equivalent method

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

45 Minutes Presentation Introduction to Sodium Chloride Equivalent

2 Method

Brainstorming

60 Minutes Presentation Determining the Isotonicity by Sodium Chloride

3 Method

Demonstration

4 05 Minutes Presentation Key Points

5 05 Minutes Presentation Evaluation

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Sodium Chloride Equivalent Method (45 minutes)

• The Sodium Chloride equivalent method (E) is the amount of sodium which has the same osmotic

effect (based on number of particles) as 1g of the drug sample calculation

• Percentage of sodium chloride for adjustment to isotonicity = 0.9 – ( % of medicament in

solution x sodium chloride equivalent of medicament)

• When adjustment is to be made with a substance other than sodium chloride first calculate the

required percentage of sodium chloride and then divide this by the sodium chloride equivalent of

the chosen adjusting substance

• Example

o Calculate the percentage of anhydrous dextrose required to render a 1% solution of ephedrine

hydrochloride iso – osmotic with body fluid

o Sodium chloride equivalent

 Ephedrine hydrochloride = 0.30

 Anhydrous dextrose = 0,18

• Therefore percentage of sodium chloride for adjustment = 0.9 – ( 1 x 0.3) == 0.6

• Equivalent percentage of anhydrous dextrose = 0.6 = 6

0.1

STEP 3: Determining the Isotonicity by Sodium Chloride Equivalent Method (60

minutes)

• Calculate the amount of NaCl required to make the following ophthalmic solution isotonic.

Atropine Sulfate 2%

NaCl qs

Aqua. dist. qs. ad. 30 ml

M.ft. isotonic solution

1. Determine the amount of NaCl to make 30 ml of an isotonic solution

2. Calculate the contribution of atropine sulfate to the NaCl equivalent

3. Determine the amount of NaCl to add to make the solution isotonic by subtracting (2) from (1)

Other substances may be used, in addition to or in place of NaCl, to render solutions isotonic.

This is done by taking the process one step further and calculating the amount of the

substance that is equivalent to the amount of NaCl calculated in step 3.

For example, boric acid is often used to adjust isotonicity in ophthalmic solutions because of

its buffering and anti-infective properties. If E for boric acid is 0.50, then the amount of boric

acid needed to replace the NaCl in step 3 can be calculated:

or, more simply:

Thus, 0.38 g or 380 mg of boric acid would be required to render the previous ophthalmic

solution isotonic

100

To determine amount of ingredients required making isotonic solution

Activity: Small Group Discussion (20 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• Calculate the percentage of sodium chloride needed to make an injection containing

morphine sulphate 1%, hyoscine hydrobromide 0.04% and sodium metabisulphate 0.1%

iso – osmotic with blood plasma

REFER Students to Pharmaceutical Calculation. 13th Edition by HOWARD C.

ANSEL: Chapter 11,for reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

• Sodium chloride equivalent

o Ephedrine hydrochloride = 0.30

o Anhydrous dextrose = 0,18

• Therefore percentage of sodium chloride for adjustment:

= 0.9 – ( 1 – 0.14) + ( 0.04 x 0.12 ) + ( 0.1 x 0.70 )

= 0.9 – (0.14 + 0.0048 + 0.07)

= 0.9 – 0.2148

= 0.6852

= 0.69

• Percentage of sodium chloride for adjustment = 0.69%

STEP 4: Key Points (5 minutes)

• The Sodium Chloride equivalent method (E) is the amount of sodium which has the same osmotic

effect (based on number of particles) as 1g of the drug sample calculation

• Percentage of sodium chloride for adjustment to isotonicity = 0.9 – ( % of medicament in

solution x sodium chloride equivalent of medicament)

101

• When adjustment is to be made with a substance other than sodium chloride first calculate the

required percentage of sodium chloride and then divide this by the sodium chloride equivalent of

the chosen adjusting substance

STEP 5: Evaluation (5 minutes)

• What is sodium chloride equivalent method (E) in determining isotonic?

• What is the percentage of sodium chloride for adjustment to isotonicity?

STEP 6: Take Home Assignment (15 minutes)

Activity: Take home Assignment (15 minutes)

ASK each individual student to do the following assignment

• Calculate the strength of sodium chloride solution which is iso – osmotic with blood

serum and tears

ALLOCATE time for students to do the assignment and submit

REFER students to recommended references

102

References

Ansel, H. C &Stocklosa, M. J. (2001). Pharmaceutical Calculations (11th ed.). Philadelphia, United

States: LIPPINCOTT WILLIAMS & WILKINS

Ansel, H. C (2010) Pharmaceutical Calculations (13rd ed.). Philadelphia, United States:

LIPPINCOTT WILLIAMS & WILKINS

Senya, S. S, Mwasha, C.Y, Muyinga, A. M, Amiri,R. I. and Mauga E.A.S.K. (2011) Tanzania

Pharmaceutical Handbook (2nd ed.). Dar eS Salaam, Tanzania: School of Pharmaceutical

Sciences.

Zatz, J.L and Teixeira, M.G. (2005). Pharmaceutical Calculation (4th ed.). New Jersey: John Wiley

& Sons, Inc

103

Session 14: Determination of Isotonicity by Molecular

Concentration Method

Total Session Time: 120 minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Explain isotonicity by molecular concentration method

• Determine the isotonicity by molecular method

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

45 minutes Presentation Isotonicity by Molecular Method

Brainstorming

60minutes Presentation Determining the Isotonicity by Molecular

3 Concentration Method

Demonstration

4 05 minutes Presentation Key Points

5 05 minutes Presentation Evaluation

104

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Molecular Concentration Method (45 minutes)

• Molecular concentration: number unit i.e. molecules or ions or both presents in a solution

• A solution containing 1g molecule of a non – ionizing solute in 22.4 liters at normal temperature

and pressure (NTP) has an atmospheric pressure of one atmosphere

• Therefore a solution containing on gram molecule in 1 litre (a mole solution) will have osmotic

pressure of 22.4 atmosphere

• The molarity or molar concentration of a solute is defined as the number of moles of solute per

liter of solution (not per liter of solvent!):

• M=N/L Where M=molarity, N = number of mole and L = 1 litre of a solution

• N =M/MW where M = mass or weight and MW = molecular weight of compound

STEP 3: Determining the Isotonicity by Molecular Concentration Method (60

minutes)

Activity: Small Group Discussion ( 30 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• Calculate MW of compound x which contains 9.06g isotonic solution given dissociation

factor is 1.8.

REFER Students to Pharmaceutical Calculation. 13th Edition by HOWARD C.

ANSEL: Chapter 11, for reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

105

From freezing point = 1.86Ni

Where N = Number of mole and i dissociation factor

N = m/ mw and i = (% x p) + (100% – %) where p = number of ions after dissociation

Now

0.52 = 1.86 x N x 1.8

N = 0.52/ 1.86 x 1.8

N = 0.1553166

But N = M/MW

MW = m/N therefore 9.06g/0.1553166

Mw =58.33

STEP 4: Key Point (5 minutes)

• Molecular concentration is the number of units i.e. molecules or ions or both present in a solution

• A solution containing 1g molecule of a non – ionizing solute in 22.4 liters at normal temperature

and pressure (NTP) has an atmospheric pressure of one atmosphere

• Therefore a solution containing one gram molecule in 1 litre (a mole solution) will have osmotic

pressure of 22.4 atmosphere

STEP 5: Evaluations (5 minutes)

• What is molecular concentration

STEP 6: Take Home Assignment (5 minutes)

Activity: Take home Assignment (15 minutes)

ASK each individual student to do the following assignment

• Compound x contains 9.07g dissociate by 80% into two ions. Calculate molecular

weight of isotonic solution

ALLOCATE time for students to do the assignment and submit

REFER students to recommended references

106

References

Ansel, H. C & Stocklosa, M. J. (2001). Pharmaceutical Calculations (11th ed.). Philadelphia, United

States: LIPPINCOTT WILLIAMS & WILKINS

Ansel, H. C (2010) Pharmaceutical Calculations (13rd ed.). Philadelphia, United States:

LIPPINCOTT WILLIAMS & WILKINS

Senya, S. S, Mwasha, C.Y, Muyinga, A. M, Amiri,R. I. and Mauga E.A.S.K. (2011) Tanzania

Pharmaceutical Handbook (2nd ed.). Dar eS Salaam, Tanzania: School of Pharmaceutical

Sciences.

Zatz, J.L and Teixeira, M.G. (2005). Pharmaceutical Calculation (4th ed.). New Jersey: John Wiley

& Sons,

107

Session 15: Calculations Involving Milliequivalent

Total Session Time: 120 minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Explain Milliequivalent

• Calculate Milliequivalent

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

• Handout 15.1: Values for some important ions

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

2 45minutes Presentation Milliequivalent

60 minutes Presentation Calculating Milliequivalent

Demonstration

4 05 minutes Presentation Key Points

5 05 minutes Presentation Evaluation

108

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (05 Minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Milliequivalent (45 Minutes)

• The equivalent weight of an element is the gram atomic weight divided by its valency OR

• A Milliequivalent of an ion is the ionic weight in mg divided by the valence of that ion

• Divide the Equivalent by 1000, and you get a

• For example, Na has an atomic weight of 23. So 23 mg of Na+ in solution means 1 mmol of Na+

is in solution. We could also say 1 mEq of Na+ is in solution.

• Ca has an atomic weight of 40. So 40 mg of Ca2+ in solution means 1 mmol of Ca2+ is in solution.

In this case, 2 mEq of Ca is in solution.

1mEq = ionic weight in mg e.g. 1mEqCa2+ = 40 = 20mg

Valency 2

1mEqCa is equivalent to 20mg calcium

The number of mEq of each ion obtained from a salt in solution therefore depends on the valency

of the ion e. g. Sodium chloride has 1 Na+ and Cl- in each molecule and both have the valency of

one

1mEq Na+ = 23 = 23mg sodium

1mEq Cl = 35. 5 = 35.5mg sodium

Therefore, 58.5mg sodium chloride provide 1 mEq Na+ and 1 mEq Cl-

• In this case mmol and mEq give numerically the same results, because both ions have the valency

of one

CaCl2 2H2O provides 1 Ca2+ which has the valency of two and Cl- with the valency of one

1mEqCa2+ = 40 = 20mg calcium

–

1mEqCl = 35 = 35.5mg chloride

109

Hence 147mg CaCl2.2H2O will provide 2mEq Ca2+ and 2 mEq Cl;

(20 x 2) + (35.5 x 2) + (18 x 2) = 147

N.B: The molecular weight of H2O is 18

• Therefore, the amount of salt containing 1 mEq of specified ion is calculated by the following

equation:

• Mg salt containing 1 mEq of specified ion = molecular weight of salt

Valency of specified ion x number of specified ions in the

molecule

• E.g. How many mg of calcium chloride are needed to provide 1mEq of Ca2+ and 1 mEq Cl?

• MgCaCl2.2H2O containing 1mEq of Ca2+ = 147 = 73.5mg

2×1

• MgCaCl2.2H2O containing 1mEq of Cl = 147 = 73.5mg

–

2×1

•

73.5mg CaCl2 .2H2O provide 1mEq Ca and 1 mEq Cl-

• When g or mg salt are stated the number of mEq can be calculated by simple proportion

e.g. How many mEq Na+ are contained in 351mg NaCl?

1 = x x = 1 x 351 = 6mEq

58.5 351 58.5

• The number of mEq of anions cations in any amount of salt is always the same, whereas the

number of mmol of anions and cations differs with certain salts, depending on the number of ions

in the molecule

• Conversion of mmol to mEq and vice versa can be done by the following equation:

Mmol == mEq

Valency

Examples

• Molecular weights can be obtained from the table below

1. How many mg of sodium phosphate contain 1mEq HPO42-

Mg Na2HPO4.12H2O containing 1mEq HPO42- = 358 = 179mg

2X1

179mg ofNa2HPO4.12H2O provide 1mEq HPO4

• According to the note above, 179mg of the salt will provide as well 1mEq Na+

2. A solution contains 90 mEq Na+, 60mEq K+ and 150 mEq Cl- per litre. Convert to g/L

• A convenient way to solve the question is first to arrange the mEq in a table, so that the

composition of the salt is obvious

110

Cations Anions

Na+ K +

Cl-

90 90

60 60

150 150

NaCl: As 1 mEq Na+ or Cl- is provided by 58.5mg NaCl, then 90mEq will be provided by

58.5 x 90

58.5x 90 = 5265mg

KCL: The amount is found respectively

74.5 x 60 = 4470mg

Therefore the solution contains 5.265g NaCl and 4.47g KCL per litre

STEP 3: Calculating Milliequivalent (60 minutes)

Activity: Small Group Discussion ( 30 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• 367mg calcium chloride provide how many mmol Ca2+ and how many mmol Cl-?

REFER Students to Pharmaceutical Calculation. 13th Edition by HOWARD C.

ANSEL: Chapter 11,for reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

1mmol Ca2+ = 147 == 147mg

111

Therefore: 1 = x x = 1 x 367 = 2.49 = 2.5 mmol Ca2+

147 367, 147

1mmol Cl- = 147mg = 73.5mg

Therefore:

1 = x x = 1 x 367 = 4.99 = 5mmol Cl-

73.5 367 73.5

367mg calcium chloride provide 2.5mmol Ca2+ and 5 mmol Cl-

Handout 15.1: Values for some important ions

STEP 4: Key Points (5 minutes)

• A Milliequivalent of an ion is the ionic weight in mg divided by the valence of that ion

• The number of mEq of anions cations in any amount of salt is always the same, whereas the

number of mmol of anions and cations differs with certain salts, depending on the number of ions

in the molecules

STEP 5: Evaluation (5 minutes)

• What is equivalent weight of an element?

• What is Millequivalent?

STEP 6: Take Home Assignment (15 minutes)

Activity: Take home Assignment (15 minutes)

ASK each individual student to do the following assignment

• Calculate the strength of sodium chloride solution which is iso – osmotic with blood

serum and tears

ALLOCATE time for students to do the assignment and submit

REFER students to recommended references

112

Handout 15.1: Values for some important ions

113

References

Ansel, H. C &Stocklosa, M. J. (2001). Pharmaceutical Calculations (11th ed.). Philadelphia, United

States: LIPPINCOTT WILLIAMS & WILKINS

Ansel, H. C (2010) Pharmaceutical Calculations (13rd ed.). Philadelphia, United States:

LIPPINCOTT WILLIAMS & WILKINS

Senya, S. S, Mwasha, C.Y, Muyinga, A. M, Amiri,R. I. and Mauga E.A.S.K. (2011) Tanzania

Pharmaceutical Handbook (2nd ed.). Dar eS Salaam, Tanzania: School of Pharmaceutical

Sciences.

Zatz, J.L and Teixeira, M.G. (2005). Pharmaceutical Calculation (4th ed.). New Jersey: John Wiley

& Sons, Inc

114

Session 16: Calculations Involving Millimoles

Total Session Time: 120 minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give overview of calculations involving Millimoles

• Perform calculations involving Millimoles

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

• Handout 11.1 Powders and granules for oral administration

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

2 45minutes Presentation Introduction to Calculations Involving Millimoles

60 minutes Presentation Performing Calculations Involving Millimoles

Demonstration

4 05 minutes Presentation Key Points

5 05 minutes Presentation Evaluation

115

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Millimoles (45 minutes)

• A Millimole (mmol) of an element, a compound, or an ion is its atomic, molecular, or ionic

weight respectively e.g. the ionic weight of Ca2+ is 40, therefore, 1 mmol Ca2+ = 40mg calcium

• The number of mmol of each ion obtained from a salt in solution depends on the number of each

ion in the molecule of the salt. e.g. Sodium chloride (NaCl, mol wt.: 58.5) has 1 Na and 1 Cl in

each molecule. Hence 1 mmol NaCl ( 58.5mg) provides 1 mmol Na (23mg) and 1 mmol Cl

(35.5mg)

• Calcium chloride (CaCl2.2H2O, mol wt.: 147) has 1 Ca2+ and 2Cl in each molecule. Hence

1mmolCaCl2.2H2O (147mg) provides 1 mmol Ca2+ ( 40mg) and 2mmol Cl(71mg)

• Therefore the amount of mg salt containing 1 mmol of a specified ion is calculated by the

following equation:

mg salt containing 1 mmol of specified ion = molecular weight of the salt

Number of specified ions in the molecule

Example:

• How many mg calcium chloride are needed to provide 1 mmol of Ca2+ and 1 mmol of Cl-

• mgCaCl2.2H2O containing 1 mmol of Ca2+= 147 = 147 mg

• 147mg CaCl2. 2H2O will provide 1 mmol Ca2+

• mgCaCl2.2H2O containing 1 mmol of Cl- = 147 = 73.5mg

• 73.5 mg CaCl2. 2H2O will provide 1 mmol Cl-

• When g or mg salt are stated the number of mmol can be calculated by simple proportion

116

Example:

• How many mmol Cl are obtained from234mg sodium chloride?

• 58.5mg NaCl provide 1 mmol Cl-, therefore;

1 == x x = 1 x 234 = 4mmol

58.5 234 58.5

234mg NaCl provide 4 mmol Cl-

STEP 3: Calculating Millimoles (60 minutes)

Activity: Small Group Discussion ( 40 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• 367mg calcium chloride provide how many mmol Ca2+ and how many mmol Cl-?

REFER Students to Pharmaceutical Calculation. 13th Edition by HOWARD C.

ANSEL: Chapter 11, for reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

1mmol Ca2+ = 147 == 147mg

Therefore: 1 = x x = 1 x 367 = 2.49 = 2.5 mmol Ca2+

147 367 147

–

1mmol Cl = 147mg = 73.5mg

117

Therefore:

1 = x x = 1 x 367 = 4.99 = 5mmol Cl-73.5 367

73.5

367mg calcium chloride provide 2.5mmol Ca2+ and 5 mmol Cl-

STEP 4: Key Points (5 minutes)

• A Millimole (mmol) of an element, a compound, or an ion is its atomic, molecular, or ionic weight

respectively e.g. the ionic weight of Ca2+ is 40, therefore, 1 mmol Ca2+ = 40mg calcium

• The number of mmol of each ion obtained from a salt in solution depends on the number of each ion

in the molecule of the salt. e.g. Sodium chloride (NaCl, mol wt.: 58.5) has 1 Na and 1 Cl in each

molecule. Hence 1 mmol NaCl ( 58.5mg) provides 1 mmol Na (23mg) and 1 mmol Cl (35.5mg)

STEP 5: Evaluation (5 minutes)

• What is Millimole (mmol) of an element?

STEP 6: Take Home Assignment (15 minutes)

Activity: Take home Assignment (15 minutes)

ASK each individual student to do the following assignment

• Calculate the strength of sodium chloride solution which is iso – osmotic with blood

serum and tears

ALLOCATE time for students to do the assignment and submit

REFER students to recommended references

118

References

Ansel, H. C &Stocklosa, M. J. (2001). Pharmaceutical Calculations (11th ed.). Philadelphia, United

States: LIPPINCOTT WILLIAMS & WILKINS

Ansel, H. C (2010) Pharmaceutical Calculations (13rd ed.). Philadelphia, United States:

LIPPINCOTT WILLIAMS & WILKINS

Senya, S. S, Mwasha, C.Y, Muyinga, A. M, Amiri,R. I. and Mauga E.A.S.K. (2011) Tanzania

Pharmaceutical Handbook (2nd ed.). Dar eS Salaam, Tanzania: School of Pharmaceutical

Sciences.

Zatz, J.L and Teixeira, M.G. (2005). Pharmaceutical Calculation (4th ed.). New Jersey: John Wiley

& Sons, Inc

119

Session 17: Calculations Involving Milliosmoles (mOsmol)

Total Session Time: 120 minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give introduction to calculations involving milliosmoles

• Perform calculations Involving Milliosmoles

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and compute

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

45 Minutes Introduction to Calculations Involving

2 Presentation Milliosmoles

60 Minutes Presentation Performing Calculation Involving Milliosmoles

Demonstration

4 05 Minutes Presentation Key Points

5 05 Minutes Presentation Evaluation

120

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Introduction to Milliosmoles (45 minutes)

• The osmotic activity of a solution may be stated in terms of Milliosmoles which is an expression

of the osmotic activity of 1 Millimole

• The term Osmolarity is used to express the strength in mOsmol per liter and indicates the total

ionic concentration of the solution

• Labels of some pharmacopoeia solutions that provide intravenous replenishment of fluids,

nutrients, electrolytes and the osmotic diuretic mannitol are required to state osmolar

concentration.

• This information indicates to the practitioner whether the solution is hypotonic, isotonic or

hypertonic with regard to biologic fluids and membranes

• Since the unit that is used to measure osmotic concentration is Milliosmoles then;

o For non – electrolytes e.g. dextrose 1 mmol (formulary weight in mg) represents

1 mOsmol

o For electrolytes, the total number of particles in solution depends on the degree of

dissociation of the substance in question, assuming complete dissociation

• 1 mmol of NaCl represents 2 mOsmol ( Na+ and Cl-) of the total particles

• 1 mmol of CaCl2 represents 3 mOsmol ( Ca2+ and 2Cl-) of the total particles

• 1 mmol of Sodium citrate (Na3C6H5O7) represents 4 mOsmol ( 3Na+ -C6H5O7) of the total

particles

• The milliosmolar value of separate ion of an electrolyte may be obtained by dividing the

concentration in mg per liter of an ion by its atomic weight

• The milliosmolar value of the whole electrolyte in solution is equal to the sum of the milliosmolar

value of separate ions

• According to USP, the ideal osmolar concentration may be calculated using the following

equation:

• mOsmol/L = Weight of the substance(in g/L) x Number of specie x 1000

Molecular weight (in g)

121

• Examples

o A solution contains 5% anhydrous dextrose in water for injection. How many mOsmol per

liter are represented by this concentration?

o Formula weight of anhydrous dextrose = 180

o 1mmol of anhydrous dextrose (= 180 mg) = 1 mosmol

o 5% solution contains 50g or 50,000mg/L

o Therefore:

 mOsmol/L = 50,000 = 278mOsmol/

180

 OR Using USP equation:

 mOsmol/L = 50 x 1000 = 278 mOsmol/ L

o 180

STEP 3: Performing Calculations Involving Milliosmoles (60 Minutes)

Activity: Small Group Discussion ( 40 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• How many mOsmol are represented in a liter of a 0.9% sodium chloride solution

REFER Students to Pharmaceutical Calculation. 13th Edition by HOWARD C.

ANSEL: Chapter 11, for reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

Formula weight of NaCl = 58.5

1 mmol of NaCl (= 58.5mg) = 2 mOsmol

900mg of NaCl per 100mL = 9000mg NaCl per liter

Then by using proportion:

58.5mg = 2mOsmol x = 9000 x 2

9000mg x mOsmol 58.5

X = 307.7 = 308mOsmol/

122

STEP 4: Key Points (5 minutes)

• Milliosmoles (mOsmol) is an expression of the osmotic activity of 1 Millimole

• The osmotic activity of a solution may be stated in terms of Milliosmoles which is an expression

of the osmotic activity of 1 Millimole

• The term Osmolarity is used to express the strength in mOsmol per liter and indicates the total

ionic concentration of the solution

• This information indicates to the practitioner whether the solution is hypotonic, isotonic or

hypertonic with regard to biologic fluids and membranes

STEP 5: Evaluation (5 minutes)

• What is Milliosmoles?

• What are the uses of Osmolarity?

STEP 6: Take Home Assignment (15 Minutes)

Activity: Take home Assignment (15 minutes)

ASK each individual student to do the following assignment

• A solution contains 156mg of k+ ions per 100 mL. How many mOsmol are represented

in a liter of the solution?

ALLOCATE time for students to do the assignment and submit

REFER students to recommended references

123

References

Ansel, H. C &Stocklosa, M. J. (2001). Pharmaceutical Calculations (11th ed.). Philadelphia, United

States: LIPPINCOTT WILLIAMS & WILKINS

Ansel, H. C (2010) Pharmaceutical Calculations (13rd ed.). Philadelphia, United States:

LIPPINCOTT WILLIAMS & WILKINS

Senya, S. S, Mwasha, C.Y, Muyinga, A. M, Amiri,R. I. and Mauga E.A.S.K. (2011) Tanzania

Pharmaceutical Handbook (2nd ed.). Dar eS Salaam, Tanzania: School of Pharmaceutical

Sciences.

Zatz, J.L and Teixeira, M.G. (2005). Pharmaceutical Calculation (4th ed.). New Jersey: John Wiley

& Sons, Inc

124

Session 18: Calculations Involving Osmolarity

Total Session Time: 120 minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give introduction to calculation involving Osmolarity

• Concept on osmolarity vs. osmolality

• Perform calculations Involving Osmolarity

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and compute

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Tasks

2 40 Minutes Presentation Introduction to Calculation Involving Osmolarity

25 Minutes Presentation Concept on Osmolarity vs. Osmolality

40 Minutes Presentation Performing Calculation Involving Osmolarity

Demonstration

4 05 Minutes Presentation Key Points

5 05 Minutes Presentation Evaluation

125

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Introduction to Calculation Involving Osmolarity (40 Minutes)

Osmolarity

Osmolarity is defined as the number of osmoles of solute per liter (L) of solution. It is expressed in

terms of osmol/L or Osm/L. Osmolarity depends on the number of particles in a chemical solution,

but not on the identity of those molecules or ions.

Sample Osmolarity Calculations

A 1 mol/L NaCl solution has an osmolarity of 2 osmol/L. A mole of NaCl dissociates fully in water

to yield two moles of particles: Na+ ions and Cl- ions. Each mole of NaCl becomes two osmoles in

solution.

A 1 M solution of sodium sulfate, Na2SO4, dissociates into 2 sodium ions and 1 sulfate anion, so each

mole of sodium sulfate becomes 3 osmoles in solution (3 Osm).

To find the osmolarity of a 0.3% NaCl solution, you first calculate the molarity of the salt solution

and then convert the molarity to osmolarity.

Convert percent to molarity:

0.03 % = 3 grams

100 ml = 3 grams / 0.1 L = 30 g/L molarity NaCl = moles / liter = (30 g/L) x (1 mol /

molecular weight of NaCl)

Look up the atomic weights of Na and Cl on the periodic table and add the together to get the

molecular weight. Na is 22.99 g and Cl is 35.45 g, so the molecular weight of NaCl is 22.99 + 35.45,

which is 58.44 grams per mole.

Plugging this in:

Molarity of the 3% salt solution = (30 g/L) / (58.44 g/mol)

molarity = 0.51 M

You know there are 2 osmoles of NaCl per mole, so:

Osmolarity of 3% NaCl = molarity x 2

Osmolarity = 0.51 x 2

Osmolarity = 1.03 Osm

126

STEP 3: Concept on Osmolarity vs. Osmolality (25 Minutes)

• Osmolality and osmolarity are units of measurement. Osmolality is the number of osmoles of

solute in a kilogram of solvent, while osmolarity is the number of osmoles of solute in a litre of

solution. Osmolarity is the concentration of an osmotic solution.

• Osmolality is convenient to use because the amount of solvent remains constant, regardless of

changes in temperature and pressure.

• While osmolarity is easy to calculate, it's less difficult to determine because the volume of

solution changes according to temperature and pressure. Osmolarity is most commonly used when

all measurements are made at a constant temperature and pressure.

• If osmolality is the number of osmoles of solute in a kilogram of solvent, then osmolarity is the

number of osmoles of solute in a litre of solution.

• Osmolarity deals with the concentration of an osmotic solution, while osmolality deals with the

concentration of particles in a fluid.

• It is easier to determine the osmolality than the osmolarity. Osmolarity is expressed as Osm/L,

and osmolality is expressed as Osm/Kg.

• Osmolality is used to determine medical conditions like diabetes, shock and dehydration, while

osmolarity is used for the detection of the concentration of dissolved particles in urine.Osmolality

is the commonly used method of measurement in Osmometry.

• When the concentration of solutes is very low, the osmolality and osmolarity are similar.

127

STEP 3: Performing Calculations Involving Osmolarity (40 Minutes)

Activity: Small Group Discussion ( 20 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• How many mOsmol are represented in a liter of a 0.9% sodium chloride solution

REFER Students to Pharmaceutical Calculation. 13th Edition by HOWARD C.

ANSEL: Chapter 11, for reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

Formula weight of NaCl = 58.5

1 mmol of NaCl (= 58.5mg) = 2 mOsmol

900mg of NaCl per 100mL = 9000mg NaCl per liter

Then by using proportion:

58.5mg = 2mOsmol x = 9000 x 2

9000mg x mOsmol 58.5

X = 307.7 = 308mOsmol/L

STEP 4: Key Points (5 Minutes)

• Milliosmoles (mOsmol) is an expression of the osmotic activity of 1 Millimole

• A distinction also should be made between the terms osmolarity and osmolality. Whereas

Osmolarity is the milliosmoles of solute per liter of solution while osmolality is the milliosmoles

of solute per kilogram of solvent. For dilute aqueous solutions, osmolarity and osmolality are

nearly identical.

• For more concentrated solutions, however, the two values may be quite dissimilar. The

Pharmaceutical personnel should pay particular attention to a product‟s label statement regarding

molarity versus molality.

128

STEP 5: Evaluation (5 Minutes)

• What is Milliosmoles?

• What are the difference between osmolarity and osmolality?

STEP 6: Take Home Assignment (15 minutes)

Activity: Take home Assignment (15 minutes)

ASK each individual student to do the following assignment

• A solution contains 156mg of k+ ions per 100 mL. How many mOsmol are represented

in a liter of the solution?

ALLOCATE time for students to do the assignment and submit

REFER students to recommended references

129

References

Ansel, H. C &Stocklosa, M. J. (2001). Pharmaceutical Calculations (11th ed.). Philadelphia, United

States: LIPPINCOTT WILLIAMS & WILKINS

Ansel, H. C (2010) Pharmaceutical Calculations (13rd ed.). Philadelphia, United States:

LIPPINCOTT WILLIAMS & WILKINS

http://www.differencebetween.net/science/difference-between-osmolality-and-

osmolarity/#ixzz5SIJfXc7h

Senya, S. S, Mwasha, C.Y, Muyinga, A. M, Amiri,R. I. and Mauga E.A.S.K. (2011) Tanzania

Pharmaceutical Handbook (2nd ed.). Dar eS Salaam, Tanzania: School of Pharmaceutical

Sciences.

Zatz, J.L and Teixeira, M.G. (2005). Pharmaceutical Calculation (4th ed.). New Jersey: John Wiley

& Sons, Inc

130

Session 19: Calculations Involving Constituted Solutions

Total Session Time: 120minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give overview of calculations involving constituted solutions

• Perform calculations involving constituted solutions

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

45minutes Introduction to Calculations Involving Constituted

2 Presentation Solutions

60 minutes Presentation Performing Calculations Involving Constituted

3 Solutions

Demonstration

4 05 minutes Presentation Key Points

5 05 minutes Presentation Evaluation

131

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Introduction to Calculations Involving Constituted Solutions (45

Minutes)

• Process of mixing and diluting solutions

• Parts of Solutions

Terms

• Solute

o Substance to be dissolved or diluted

o Can be either solid or liquid

• Solvent

o Substance (liquid) that dissolves another substance to prepare solution

o Often referred to as diluent

• Solution

o Resulting mixture of solute plus solvent

Caution

o Before reconstituting injectable drugs, read and follow label or package insert directions

carefully

o Check drug

o Check diluent dates

• When reconstituting injectable medications, must determine both type and amount of diluent to be

used

o Sterile water and 0.9 percent NaCl commonly used

o Some drugs supplied with special diluent

o Determine volume in mL of diluent to be used

132

o Check that route noted on drug label matches route ordered

o Reconstitute drug and note resulting supply dosage on vial

o Note if single-dose or multiple-dose vial

Example Drug Label

133

STEP 3; Performing Calculations Involving Constituted Solutions (60 Minutes)

Activity: Small Group Discussion ( 30 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• Reconstituting Parenteral Solutions: Single Strength

o Order: Zithromax 400 mg IV daily for 2 days

o Available: Zithromax 500 mg vial for IV infusion

o Drug is in powder form with directions on label that state, “Constitute to 100 mg/mL

with 4.8 mL of Sterile Water for Injection

REFER Students to Pharmaceutical Calculation. 13th Edition by HOWARD C.

ANSEL: Chapter 11, for reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

Procedure:

1. How much and what type of diluent is needed?

• 4.8 mL of sterile water

2. What is the dosage concentration after reconstitution?

• 100 mg per mL

3. What is the total volume after reconstitution?

• 5 mL

4. Given the ordered dose, how many doses are available in the vial?

• One

To reconstitute Zithromax:

• Choose 5 mL syringe

• Withdraw 4.8 mL of sterile water

• Add 4.8 mL of sterile water to Zithromax powder and shake well

Determine amount needed for dose ordered

1. Convert

• No conversion needed

2. Think

• Need 400 mg

134

Have 100 mg per mL

• Need four times that amount

3. Calculate

Dosage on hand = Amount on hand

Dosage desired X Amount desired

100 mg = 400 mg

1 mL X

100 X = 400

100 X= 400 X = 4 mL

100 100

Withdraw 4 mL of reconstituted Zithromax using 5 mL syringe

• Further dilute and give IV

• Since single-dose vial, discard any remaining drug

Reconstituting Parenteral Solutions: Multiple Strength

• Some parenteral powdered medications have directions for preparing several different solution

strengths

• Penicillin G potassium 1,000,000 units vial

Reconstitution instructions note four different solution concentrations as determined by amount of

diluent added

Units per mL

mL Diluent

20 mL 50,000

10 mL 100,000

4 mL 250,000

1.8 mL 500,000

• Order: Penicillin G potassium 300,000 units IM every 6 h for adult patient

o Available: Penicillin G potassium 1,000,000 unit vial

o Given the reconstitution concentrations on the previous slide, which should you use when

preparing to administer the ordered dose?

• Consider:

o Dose ordered

o Patient receiving dose

o Consider:

o Volume and concentration that results with each noted diluent volume

o Smaller the amount of diluent added, stronger the resulting solution concentration

135

o Consider maximum recommended volumes for injection by patient and parenteral route

• Considering previously mentioned factors, adding 4 mL of diluent results in reasonable volume

and medication concentration

o Results in concentration of 250,000 units per mL

o How many mL are needed to deliver ordered dose of 300,000 units?

1. Convert

o No conversion necessary

2. Think

o 250,000 units in 1 mL need 300,000 units

o Slightly more than what is available in 1 mL

250,000 units = 300,000unit

1mL x mL

250, 000x = 300,000

250,000 = 300,000 x = 1.2 mL

250,000 250,000

o Rule

o When reconstituting multiple-dose injectable medications:

o Label reconstituted drug noting resulting supply dosage

o In previous example, 250,000 units per mL

o Verify length of drug potency and storage directions

o Label on penicillin G potassium notes that solution “may be kept in refrigerator for one (1)

week”

o Complete label of reconstituted multiple-dose vial, noting:

 Date and time of preparation

 Supply dosage

 Length of potency

o Expiration date

o Complete label of reconstituted multiple-dose vial, noting:

 Storage directions

 Own initials

o Different IM and IV Reconstitution Instructions

 Reconstitution instructions can differ in amount and/or type of diluent based on

administration route

 Must carefully check route ordered and related reconstitution directions

o Complete label of reconstituted multiple-dose vial, noting:

 Storage directions

 Own initials

o Different IM and IV Reconstitution Instructions

136

o Reconstitution instructions can differ in amount and/or type of diluent based on

administration route

o Must carefully check route ordered and related reconstitution directions

• Reconstitution of Non-Injectable Solutions

• Examples:

o Nutritional formulas

o Irrigating solutions

o Usually need to dilute liquid concentrate to weaker solution

• Solution Concentration

o Amount of solvent used determines final solution concentration or strength

 Fraction expresses strength of solution made from liquid concentrate

o Numerator

o Number of parts of solute

• Fraction expresses strength of solution made from liquid concentrate

o Denominator

• Number of parts of solution

o Difference between denominator (final solution) and numerator (parts of solute) is number of

parts of solvent

• Solution Concentration Example:

1 Strength nutritional formula

1 part concentrate

3 parts total solution

3 – 1 = 2 parts of solvent

• Water

• Calculating Solutions

• To prepare solutions:

1. Apply ratio-proportion to find amount of solute (X)

Solution strength = X amount of solute

Quantity of desired solution

2. Quantity of desired solution – Amount of solute = Amount of solvent

137

• Solution Calculation Example

Physician orders patient‟s wound irrigated with 2

strength hydrogen peroxide and normal saline solution every four hours while patient is awake

• 60 mL per irrigation for three irrigations during 12-hour shift

o Prepare 60mL x 3 irrigations = 180mL total solution

• How much stock hydrogen peroxide and normal saline is needed?

1. Convert

o No conversion necessary

2. Think

o Need2 strength

2 parts solute (concentrated hydrogen peroxide) to 3 total parts solution

o Amount of solvent is 3 – 2 = 1 part saline

o For 180 mL of solution, need2 as solute (120 mL) and1 as solvent (60 mL)

3. Calculate

2 = x mL

3 180

3x = 360

3 x = 360 x = 120mL

o 120 mL of full strength hydrogen peroxide and 60 mL of normal saline are needed to make

desired solution

STEP 4: Key Point (Minutes 5)

• Solute is a substance to be dissolved or diluted and can be either solid or liquid, solvent is a

substance (liquid) that dissolves another substance to prepare solution and often referred to as

diluent and solution is a resulting mixture of solute plus solvent

• Caution; Before reconstituting injectable drugs, read and follow label or package insert directions

carefully, check drug and check diluent dates

STEP 5: Evaluations (Minutes 5)

• What are the solvents?

• What are the Cautions before reconstituting injectable drugs?

138

References

Ansel, H. C &Stocklosa, M. J. (2001). Pharmaceutical Calculations (11th ed.). Philadelphia, United

States: LIPPINCOTT WILLIAMS & WILKINS

Ansel, H. C (2010) Pharmaceutical Calculations (13rd ed.). Philadelphia, United States:

LIPPINCOTT WILLIAMS & WILKINS

Senya, S. S, Mwasha, C.Y, Muyinga, A. M, Amiri,R. I. and Mauga E.A.S.K. (2011) Tanzania

Pharmaceutical Handbook (2nd ed.). Dar eS Salaam, Tanzania: School of Pharmaceutical

Sciences.

Zatz, J.L and Teixeira, M.G. (2005). Pharmaceutical Calculation (4th ed.). New Jersey: John Wiley

& Sons, Inc

139

Session 20: Calculations Involving Intravenous Admixture

Total Session Time: 120minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give overview of calculations involving intravenous admixture

• Perform calculations Involving of intravenous admixture

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

45minutes Introduction to calculations involving intravenous

2 Presentation admixture

60 minutes Presentation Performing Calculations Involving Intravenous

3 Admixture

Demonstration

4 05 minutes Presentation Key Points

5 05 minutes Presentation Evaluation

140

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Introduction to Calculations Involving Intravenous Admixture (45

Minutes)

• The preparation of intravenous admixtures involves the addition of one or more drugs to large

volume sterile fluid such as sodium chloride injection, dextrose injection, lactated ringer‟s

injection and others.

• The additives are generally in the form of small volume sterile solutions packed in ampules, vials,

small – volume minibags for use as piggybacks, or sterile solids, some requiring constitution with

a sterile solvent before transfer

• Although a wide variety of drugs and drug combinations are used in preparing dilute infusions for

intravenous therapy, some of the more common additives include electrolytes, antibiotics,

vitamins, trace minerals, heparin, and, in some instances, insulin

• In any properly administered intravenous admixture programme, all basic fluids(large volume

solutions), additives (already in solution or extemporaneous constituted), and calculations must be

carefully checked against the medication

• Patient care facilities often adopt standard concentrations of intravenous solutions of commonly

used drugs to provide uniformity within the institution

• Common examples are dopamine 400mg in 250mL of D5W, insulin 25 units in250mL of NS, and

nitroglycerin 50mg in 250mL D5W.

• In preparing these standard concentrations, the pharmacist withdraws the determined volume

From an ampule or vial containing the concentrated drug solution and transfers it to the specified

volume of D5W, NS, or other intravenous fluid.

141

STEP 3: Performing Calculations Involving Intravenous Admixture (60minutes)

Activity: Small Group Discussion ( 30 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• A medication order for a patient weighing 154lb. calls for 0.25mg of amphotericin B per

kilogram of body weight to be added to 500mL of 5% dextrose injection. If amphotericin

B is to be obtained from a constituted injection that contains 50mg/10mL, how many

milliliters should be added to the dextrose injection?

REFER Students to Pharmaceutical Calculation. 13th Edition by HOWARD C.

ANSEL: Chapter 11, for reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

1kg == 2.2 lb.

154(lb.) = 70

2.2(lb.)

0.25mg x 70 = 17.5mg

Constituted solution contains 50 mg/ 10mL

50 (mg) == 10 (mL) x = 3.5mL

17.5(mg) x (mL)

OR, solving by dimensional analysis:

154 lb. x1kg x 0.25mg x 10mL = 3.5mL

2.2lb 1kg 50mg

142

STEP 4: Key Points (5 minutes)

• The preparation of intravenous admixtures involves the addition of one or more drugs to large

volume sterile fluid such as sodium chloride injection, dextrose injection, lactated ringer‟s

injection and others.

• The additives are generally in the form of small volume sterile solutions packed in ampules, vials,

small – volume minibags for use as piggybacks, or sterile solids, some requiring constitution with

a sterile solvent before transfer

STEP 5: Evaluation (5 minutes)

• What are the procedures for preparation of intravenous admixtures?

STEP 6: Take Home Assignment (15 minutes)

Activity: Take home Assignment (15 minutes)

ASK each individual student to do the following assignment

• An intravenous infusion is to contain 15mEq of potassium ion and 20mEq of sodium

ion in 500mL of 5%. Using potassium chloride injection containing 6g/30mL and

0.9% sodium chloride injection, how many milliliters of each should be used to supply

the required ions?

ALLOCATE time for students to do the assignment and submit

REFER students to recommended references

143

References

Ansel, H. C &Stocklosa, M. J. (2001). Pharmaceutical Calculations (11th ed.). Philadelphia, United

States: LIPPINCOTT WILLIAMS & WILKINS

Ansel, H. C (2010) Pharmaceutical Calculations (13rd ed.). Philadelphia, United States:

LIPPINCOTT WILLIAMS & WILKINS

Senya, S. S, Mwasha, C.Y, Muyinga, A. M, Amiri,R. I. and Mauga E.A.S.K. (2011) Tanzania

Pharmaceutical Handbook (2nd ed.). Dar eS Salaam, Tanzania: School of Pharmaceutical

Sciences.

Zatz, J.L and Teixeira, M.G. (2005). Pharmaceutical Calculation (4th ed.). New Jersey: John Wiley

& Sons, Inc

144

Session 21: Calculations Involving Rate of Flow of Intravenous

Fluid

Total Session Time: 120minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give overview of calculations involving rate flow of Intravenous Fluid

• Perform calculations Involving rate of flow of Intravenous

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

45minutes Introduction to Calculations Involving Rate Flow

2 Presentation of Intravenous Fluid

60 minutes Presentation Performing Calculations Involving Rate of flow

3 of Intravenous Fluids

Demonstration

4 05 minutes Presentation Key Points

5 05 minutes Presentation Evaluation

145

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Rate of Flow of Intravenous Fluid (45 minutes)

• On medication orders, the physician specifies the rate of flow of intravenous fluids in milliliters

per minute, drops per minute, amount of drug(as milligrams per hour), or, more frequently, as the

approximate duration time of administration of the total volume of the infusion.

• Pharmacist may be called on to perform or check rate of flow calculations as those described in

the following example problems in this session

• Oftentimes, the following equation finds use in rate – of flow calculations

Rate of flow (drops/minute) == Volume infusion (mL) x Drip set Drops/m

Time (minutes)

• In common usage are macro sets that deriver 10, 15, or 20 drops per milliliter and micro drip or

mini drip sets that deriver 60 drops per milliliter

STEP 3: Performing Calculations Involving Rate of Flow of Intravenous Fluid

(60minutes)

Activity: Small Group Discussion (30 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• A medication order calls for 100mL of D5W to be administered over an 8-hour period.

Using an IV administration set that drivers 10 drops/mL, how many drops per minute

should be delivered to the patient?

REFER Students to Pharmaceutical Calculation. 13th Edition by HOWARD C.

ANSEL: Chapter 11, for reference

ALLOW students to discuss for 20 minutes

146

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

Volume of fluid = 1000mL

8hours = 480minutes

1000(mL) = 2.08 per minute

480(minutes)

2.08mL/min x 10 (drops/mL) = 20.8 or 21 drops per minutes

OR,

Solving by the equation:

Rate of flow (drop/min) = Volume infused (mL) x Drip set (drops/mL)

Time (min)

1000mL x 10drops/mL ==20.8 or 21drops per minutes

480minutes

STEP 4: Key Points (5 minutes)

• On medication orders, the physician specifies the rate of flow of intravenous fluids in milliliters

per minute, drops per minute, amount of drug(as milligrams per hour), or, more frequently, as the

approximate duration time of administration of the total volume of the infusion.

• Pharmacist may be called on to perform or check rate of flow calculations as those described in

the following example problems in this session

STEP 5: Evaluation (5 minutes)

• What is formula used to calculate rate of flow of intravenous fluids?

147

STEP 6: Take Home Assignment (15 minutes)

Activity: Take home Assignment (15 minutes)

ASK each individual student to do the following assignment

• Ten (10) milliliters of 10% calcium gluconate injection and 10 mL of multivitamin

infusion are mixed with 500mL of a 5% dextrose injection. The infusion is to be

administered over 5 hours. If the dropper in the venoclysis set calibrates 15drops/mL,

at what rate, in drops per minutes, should the flow be adjusted to administer the

infusion over the desired time interval?

ALLOCATE time for students to do the assignment and submit

REFER students to recommended references

148

References

Ansel, H. C &Stocklosa, M. J. (2001). Pharmaceutical Calculations (11th ed.). Philadelphia, United

States: LIPPINCOTT WILLIAMS & WILKINS

Ansel, H. C (2010) Pharmaceutical Calculations (13rd ed.). Philadelphia, United States:

LIPPINCOTT WILLIAMS & WILKINS

Senya, S. S, Mwasha, C.Y, Muyinga, A. M, Amiri,R. I. and Mauga E.A.S.K. (2011) Tanzania

Pharmaceutical Handbook (2nd ed.). Dar eS Salaam, Tanzania: School of Pharmaceutical

Sciences.

Zatz, J.L and Teixeira, M.G. (2005). Pharmaceutical Calculation (4th ed.). New Jersey: John Wiley

& Sons, Inc

149

Session 22: Calculations Involving Buffer Solutions

Total Session Time: 60minutes + 6 hours of Practices

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give overview of calculations involving buffer solutions

• Perform calculations involving buffer solution

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

45minutes Introduction to Calculations Involving Buffer

2 Presentation Solutions

60 minutes Presentation Performing Calculations Involving Buffer

3 Solutions

Demonstration

4 05 minutes Presentation Key Points

5 05 minutes Presentation Evaluation

150

SESSION CONTENTS

STEP1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Buffer Solution (45 minutes)

• When a minute trace of hydrochloric acid is added to pure water, a significant increase in

hydrogen – ion concentration occurs immediately

• In similar manner, when a minute trace of sodium chloride is added to pure water, it causes a

correspondingly large increase in in the hydroxyl – ion concentration

• These changes takes place because water alone cannot neutralize even traces of acid or base, that

is, it has no ability to resist changes in hydrogen – ion concentration or pH. A solution of a neutral

salt, such as sodium chloride, also lacks this ability. Therefore it is said to be unbuffered

• The presence of certainly substances or combination of substances in aqueous solution imparts to

the system the ability to maintain a desired pH at a relatively constant level, even with the

addition of materials that may be expected to change the hydrogen – ion concentration.

• These substances or combinations of substances are called buffers, their ability to resist changes

in PH is referred to as buffer action; their efficiency is measured by the function known as buffer

capacity; solutions of them are called buffer solutions

• By definition, then, a buffer solution is a system, usually an aqueous solution, that possesses the

property of resisting changes in PH with the addition of small amounts of a strong acid or base

• Buffers are used to establish and maintain an ion activity within rather narrow limits

• In pharmacy, the most common buffer systems are used in

o The preparation of such dosage forms as injections and ophthalmic solutions, which are

placed directly into pH sensitive body fluids;

o The manufacture of formulations in which the pH must be maintained at a relatively constant

level to ensure maximum product stability: and

o Pharmaceutical tests and assays requiring adjustment to or maintenance of a specific pH for

analytic purposes

• A buffer solution is usually composed of a weak acid and a salt of the acid, such as acetic acid

and sodium acetate, or weak base and a salt of the base, such as ammonium hydroxide and

ammonium chloride

• Typical buffer systems that may be used in pharmaceutical formulations include the following

pairs; acetic acid and sodium acetate, boric acid and sodium borate, and disodium phosphate and

sodium acid phosphate

151

• Formulas for standard buffer solutions for pharmaceutical analysis are given in the united States

Pharmacopeia

• In the selection of a buffer system, due consideration must be given to the dissociation constant of

the weak acid or base to ensure maximum buffer capacity. This dissociation constant, in the case

of an acid, is a measure of the strength of acid; the more readily the acid dissociates, the higher

its dissociation constant and the stronger the acid

• Selected dissociation constants, or ka value, the dissociation constant, or Ka value, of a weak acid

is given by the equation:

Ka = (H+) (A-) Where A- == salt

(HA) HA == acid

• Because the numerical values of most dissociation constants are small numbers and may vary

over many powers of 10, it is more convenient to express them as negative logarithms

pKa = – log Ka

When equation Ka = (H+) (A-) is expressed in logarithmic form, it is written:

(HA)

pKa = – log (H+) – log salt

acid

Since pH = – log (H ):

then pKa = pH – log salt

acid

and pH = pKa + log salt

acid

152

Buffer Equation:

• The equation just derived is the Henderson –Hasselbalch equation for weak acids, commonly

known as the buffer equation

• Similarly, the dissociation constant, or Kb value, of a weak base is given by the equation:

Kb = (B+) (OH -) in which B+ = salt

(BOH) and BOH = Base

And the buffer equation for weak bases, which is derived from this relationship, may be expressed as:

pH = pKw – pKb + log base

salt

• The buffer equation is useful for calculating

o The pH of a buffer system if its composition is known

o The molar ratio of the components of a buffer system required to give a solution of a desired

pH. The equation can also be used to calculate the change in pH of a buffered solution with

the addition of a given amount of acid or base

STEP 3: Performing Calculations Involving Buffer Solutions (60 Minutes)

Activity: Small Group Discussion ( 30 minutes)

DIVIDE students in small manageable groups

ASK students to discuss in groups on the following questions

• pKa Value of a Weak Acid with known Dissociation Constant

• Calculate the pKa value of a weak acid, given its dissociation constant, Ka.

REFER

• Students to Pharmaceutical Calculation. 13th Edition by HOWARD C. ANSEL:

Chapter 11, for reference

ALLOW students to discuss for 20 minutes

ALLOW each groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

153

The dissociation constant of acetic acid is 1.75 x 105- at 250C. Calculate its pKa value

Ka = 1.75 x 10-5

And log Ka = log 1.75 + 105-

= 0.2430 – 5 = – 4.757 or – 4.76

Because pKa = – log Ka

pKa = – (-4.76) = 4 .76

STEP 4: Key Points (5 minutes)

• Buffer solution is a system, usually an aqueous solution, that possesses the property of resisting

changes in pH with the addition of small amounts of a strong acid or base

• A buffer solution is usually composed of a weak acid and a salt of the acid, such as acetic acid

and sodium acetate, or weak base and a salt of the base, such as ammonium hydroxide and

ammonium chloride

• Typical buffer systems that may be used in pharmaceutical formulations include the following

pairs; acetic acid and sodium acetate, boric acid and sodium borate, and disodium phosphate and

sodium acid phosphate

STEP 5: Evaluation (5 minutes)

• What is a buffer solution?

• What are the applications of buffer solutions in pharmacy?

154

STEP 6: Take Home Assignment (15 minutes)

Activity: Take home Assignment (15 minutes)

• pH Value of a salt /Acid Buffer System

• Calculate the pH value:

• What is the pH of a buffer solution prepared with 0.05M sodium borate and 0.005M

boric acid?

• The pKa value of boric acid is 9.24 at 250C

Note that the ratio of the components of the buffer solution is given in molar

concentrations

ALLOCATE time for students to do the assignment and submit

REFER students to recommended references

• Using the buffer equation for weak acids:

pH = pKa + log salt

acid

= 9.24 + log 0.05

0.005

= 9.24 + log 10

= 9.24 +1

= 10 .24

155

References

Ansel, H. C &Stocklosa, M. J. (2001). Pharmaceutical Calculations (11th ed.). Philadelphia, United

States: LIPPINCOTT WILLIAMS & WILKINS

Ansel, H. C (2010) Pharmaceutical Calculations (13rd ed.). Philadelphia, United States:

LIPPINCOTT WILLIAMS & WILKINS

Senya, S. S, Mwasha, C.Y, Muyinga, A. M, Amiri,R. I. and Mauga E.A.S.K. (2011) Tanzania

Pharmaceutical Handbook (2nd ed.). Dar eS Salaam, Tanzania: School of Pharmaceutical

Sciences.

Zatz, J.L and Teixeira, M.G. (2005). Pharmaceutical Calculation (4th ed.). New Jersey: John Wiley

& Sons, Inc

156

Session 23: Preservation of Pharmaceutical Product

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give overview of Preservatives which are used in pharmaceutical production

• List agent used as antimicrobial preservatives for pharmaceutical products

• List the criteria for selection of antimicrobial preservatives

• List the limitations for use of antimicrobial preservatives

• Identify functions antimicrobial preservatives for pharmaceutical products

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• Handout 23.1:Classification of compounds used as antimicrobial preservatives in pharmaceutical

formulations

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 Minutes Presentation Introduction, Learning Objectives

25 Minutes Presentation Introduction to Preservative as Used In Pharmacy

Buzzing

25 Minutes Agent Used as Antimicrobial Preservatives for

3 Presentation

Pharmaceutical Products

20 Minutes Presentation Criteria for Selection of Antimicrobial

Brainstorming Preservatives

15 Minutes Presentation Limitations for Use of Antimicrobial

Preservatives

20 Minutes Presentation Group Functions of Antimicrobial Preservatives in

Discussion Pharmaceutical Product

157

7 5 Minutes Presentation Key Points

8 5 Minutes Presentation Evaluation

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Introduction to Preservative Used in Pharmaceutical Products (25

Minutes)

• Preservative: Is a natural or synthetic chemical added to various products which helps to prevent

microbial decomposition

• Antimicrobial preservative; is a compound/ chemical substance incorporated into a

pharmaceutical formulation designed to kill or limit the growth of any micro-organism that may

gain entry into product during manufacture or use.

• Pharmaceutical preservatives: is a substance added to multiuse nonsterile liquids, ointments,

and creams and sterile injectable products to protect them from microbial contamination that may

be introduced inadvertently during use of the product (post manufacturing).

• The two words have different meanings;

o Contamination is the entry of microorganisms into the product, whilst spoilage describes the product

damage that results from microbial growth.

• Anhydrous medicines are not normally susceptible to spoilage because microbial reproduction

will not occur in the absence of water; the amount of free water available for microbial growth in

a product is determined by the water activity.

• Reducing the water activity of a product is therefore a means of protecting it against spoilage

STEP 3: Agent Used as Antimicrobial Preservatives for Pharmaceutical Products

(25 minutes)

• The following are classification of compounds used as antimicrobial preservatives in

pharmaceutical formulations:

o Acids (organic) and Saltseg:Benzoic acid, ,sorbic acid, sulphites like Sodium metabisulphite

and Sodium sulphite

158

o Alcohols eg: Benzyl alcohol, bronopol , chlorbutol , ethanol, phenoxyethanol, and

phenylethanol

o Biguanideseg: .Chlorhexidine diacetate, chlorhexidine digluconate and polyhexamethylene

o Hydroxybenzoates ( or Parabens)eg:MethylhydroxybenzoateMethylparaben),

ethylhydroxybenzoate (Ethylparaben) ,propylhydroxybenzoate (Propylparaben),

butylhydroxybenzoate

o (Butylparaben) and benzylhydroxybenzoate.

o Mercurials(Organomercurial compounds)eg: Phenylmercuric Acetate PMA), phenylmercuric

Nitrate (PMN), phenylmercuric Borate and thiomersal

o Phenols eg:Chlorocresol, cresol and bisphenol

o Quaternary ammonium compoundseg:Benzalkonium Chloride and Cetrimide

o Other agentslike: Chloroform (as Chloroform water), glycerol, sucrose, formaldehyde,

hexetidine, hexamidine and triclosan

• Depending on the concentration, the following compounds can be used both as preservatives

and disinfectants;

o Benzalkonium chloride,

o cetrimide,

o chlorocresol

o Thiomersal.

Handout 23.1: Classification of compounds used as antimicrobial preservatives

in pharmaceutical formulations

159

STEP4: Criteria for Selection of Antimicrobial Preservatives (20 minutes)

Activity: Brainstorming (10 minutes)

Ask students to brainstorm on the following question:

• What are the criteria for selection of antimicrobial preservatives?

ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• The intended use and route of administration of a product are usually the major factors limiting the

choice a preservative. However, the properties that are normally required in preservative selection

include the following:

o A broad spectrum of antimicrobial activity covering Gram-positive and Gram-negative

bacteria, yeasts and moulds, and no vulnerability to resistance development

o Low toxicity for humans, enabling it to be used in topical, oral and parenteral products

o Good solubility in water; low oil solubility

o Stability and effectiveness over a wide pH range

o Compatible with common formulation excipients and containers.

o Non-volatile, odorless and tasteless.

• Not surprisingly, no single preservative satisfies all these criteria; if there were such an

agent it would be universally used to the exclusion of all others.

• Microbial contamination of medicines arises from three principal sources:

o Raw materials (particularly water),

o Manufacturing environment

o Personnel.

o Others are raw materials of animal, vegetable or mineral origin normally have a higher level

of contamination than those made by chemical synthesis where heat, extremes of pH or

organic solvents tend to kill microorganisms

160

STEP 5: Limitations for Use of Antimicrobial Preservatives (15 Minutes)

• The range of available preservatives is quite limited, and they all suffer from one or more of the

following faults:

o Only possess good activity against bacteria or fungi, but not both.

o Exhibit reduced antimicrobial activity in certain pH ranges – several only working well in

acid conditions

o Some causes skin sensitivity reactions

o A number of microbiologically effective preservatives used in cosmetics have caused a

significant number of cases of contact dermatitis, and are thus precluded from use in

pharmaceutical creams.

o Most active antimicrobial agents are often non-selective in action

o Interact with other common excipients – several preservatives lose activity in the presence of

surfactants.

o Entrapment of preservatives within micelles of surfactants or emulsifying agents is a related

phenomenon where again, the preservative is present but unavailable to inhibit microbial

spoilage

o Interact significantly with formulation ingredients, containers as well as with patients and

microorganisms.

o Preservatives may be removed from solution by adsorption onto suspended solids like

bentonite, kaolin, magnesium trisilicate and talc

o Having excluded the more toxic, irritant and reactive agents, those remaining generally have

only modest antimicrobial efficacy.

o There are no preservatives considered sufficiently non-toxic for use in highly sensitive areas,

e.g. for injection into central nervous system tissues or for use within the eye.

o A rapid rate of kill may only be possible for relatively simple aqueous solutions such as eye-

drops or injections. For physicochemically complex systems such as emulsions and creams,

inhibition of growth and a slow rate of killing may be all that can be realistically achieved.

161

STEP 6: Functions of Antimicrobial Preservatives in Pharmaceutical Product (20

Minutes)

Activity: Small Group Discussion (15 minutes)

DIVIDE students into small manageable groups

ASK students to discuss on the following question

• What are the Functions of antimicrobial in pharmaceutical product?

ALLOW students to discuss for 15 minutes

ALLOW few groups to present and the rest to add points not mentioned

CLARIFY and SUMMARIZE by using the contents below

• The preservative‟s function is to prevent pharmaceutical product contamination and colonisation

by microbes such as bacteria, moulds and fungi after production and during its use and not to

cover for poor manufacturing or control techniques.

• Prevents microbial spoilage in non-sterile pharmaceutical products such as oral liquids, creams,

cosmetics, foods and transmission of disease to the user which might occur when the

contaminating micro-organism uses the product as a growth medium.

• It maintains sterility during use in sterile preparations such as eye-drops and multi-dose

injections.

• It maintains stability of the product so that it can be used for the required duration of time.

• Ideally preservatives should destroy pathogenic organisms.

STEP 7: Key Points (5 Minutes)

• Medicines are vulnerable to contamination and spoilage by microorganisms.

• Microorganisms should be excluded from medicines not only because they represent an infection

hazard, but also because they may degrade the active pharmaceutical ingredient, reduce the

product‟s physical stability or make it unacceptable to the patient.

162

• Preservative chemicals are required for most water-containing non-sterile products and for multi-

dose sterile products.

• There are no preservatives considered sufficiently non-toxic for use in highly sensitive areas, e.g.

for injection into central nervous system tissues or for use within the eye.

STEP 8: Evaluation (5 Minutes)

• What are pharmaceutical preservatives?

• What are criteria for selecting antimicrobial preservatives

163

References:

R.A. Fassihi, (1991), Preservation of Medicines against Microbial Contamination, in: S.A.Block

(Ed.) Disinfection Sterilization and Preservation, 4th Edition, Lea and Febiger, , pp. 871-886.

London

Scheler et al,( 2010), Preservation of liquid drug preparations for oral administration, J. Pharm. Sci,

Vol. 99, No. 1, , 357-367.New York

Meyer et al, (2007), Antimicrobial preservative use in parenteral products: Past and present, J. Pharm.

Sci., Vol. 96, No. 12,, 3155-3167. India

Narang R, Narasimhan B, Judge V, Ohlan S, Ohlan R. (2009),Evaluation of preservative

effectiveness in an official antacid preparation. ActaSci Pharm;51:225-29.

164

Handout 23.1: Classification of compounds used as antimicrobial

preservatives in pharmaceutical formulations

S/N Chemical Class Preservative’s In-use Formulation type

chemical name concentration

(%w/v)

1. Acids i.Benzoic acid 0.1 %w/v topical.

(organic)and Salts ii.Sorbic acid 0.2 %w/v Oral,

iii. Sulphites, 0.1 %w/v Parenteral

e.g. Sodium metabisulphite,

Sodium sulphite,

Sodium bisulphite,

Potassium bisulphite, Potassium

metabisulphite

2. Alcohols Benzyl alcohol 1.0 %w/v Parenteral, topical,

Bronopol 0.01-0.1 %w/v Oral, Ophthalmic.

Chlorbutol 0.3-0.5 %w/v

Ethanol 20 -70% w/v

Phenoxyethanol 1.0 %w/v

Phenylethanol , 0.25 -0.5 %w/v

3. Biguanides i. Chlorhexidine diacetate 0.01-0.1%w/v Ophthalmic, topical.

ii. Chlorhexidine digluconate, 0.01-0.1%w/v

iii. Polyhexamethylene

4. Hydroxybenzoates 1.Methylhydroxybenzoate Ophthalmic, topical,

( or Parabens) (Methylparaben) 0.4 – oral,

2.Ethylhydroxybenzoate 0.8 % w/v topical,

(Ethylparaben)

3.Propylhydroxybenzoate

(Propylparaben)

4.Butylhydroxybenzoate

(Butylparaben)

5.Benzylhydroxybenzoate

5. Mercurials i. Phenylmercuric Acetate (PMA) 0.001-002%w/v Ophthalmic,

(Organomercurial ii. Phenylmercuric Nitrate (PMN) 0.002-0.01%w/v Parenteral,

compounds) iii. Phenylmercuric Borate ophthalmic

iv. Thiomersal

6. Phenol i.Chlorocresol 0.1%w/v Parenteral, topical

ii. Cresol 0.3%w/v

iii. Bisphenol 0.25-0.5%w/v

7. Quaternary i. Benzalkonium Chloride 0.01- 0.25%w/v Parenteral,

ammonium ii.Cetrimide 0.01-0.1%w/v Ophthalmic,

compounds topical

8. Other agents i. Chloroform 0.25%v/v Oral,

(as Chloroform water) 66.7%w/w Topical

ii. Glycerol

iii. Sucrose

iv. Formaldehyde

v. Hexetidine

vi. Hexamidine

vii. Triclosan

165

← View topic-by-topic index

PDF / OFFLINE NOTES

Unataka kutumiwa notes hizi kupitia WhatsApp?Kwa notes zilizopangiliwa vizuri kwa kusoma offline au PDF, bonyeza kitufe hapa chini. Ujumbe wenye Level, Semester, Module na Topic utaandaliwa moja kwa moja.TUMIWA NOTES WHATSAPP

WhatsApp: 255620339260