Stock Solution and Dilution of Concentrated – PST04209 Compounding of Pharmaceutical Preparations

NTA Level 4 • Semester 2 • PST04209

Stock Solution and Dilution of Concentrated

Compounding of Pharmaceutical Preparations • Source Session/Topic 10
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Session 10: Stock Solution and Dilution of Concentrated

Solution

Total Session Time: 120 minutes + 20 hours of Practice

Prerequisites

• None

Learning Tasks

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

• Define Terminologies Used in this Section
• Describe Stock Solutions
• Perform Trituration, Alligation medial and Alligation alternate for Dilution of

Pharmaceutical Preparations

• Dilute Concentrated Solutions for External Use (Preparations of Antiseptics and

Disinfectants)

Resources Needed:

• Flip charts, marker pens, and masking tape
• Black/white board ,chalk/whiteboard markers
• LCD projector and computer
• Handout 10.1: Practice on Compounding of Antiseptic and disinfectant
• Worksheet 10.1: Practice on Compounding of Antiseptic and disinfectant
CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

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SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

10 minutes Presentation Definition of Terminologies Used in this

2 Section

Buzzing

3 20 minutes Presentation Stock Solutions

30 minutes Presentation Trituration, Alligation Medial and Alligation

4 Alternate for Dilution of Pharmaceutical

Preparations

45 minutes Presentation Dilution of Concentrated Solutions for External

5 Use

6 05 minutes Presentation Key Points

7 05 minutes Presentation Evaluation

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

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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 Terminologies Used in this Section (10 Minutes)

Activity: Buzzing (5 minutes)

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

• What is Stock Solution?
• What is Trituration?
• What is Alligation Medial?
• What is Alligation Alternate?

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

Stock Solution

• Are solutions of known concentration that are frequently prepared for convenience in

dispensing. They are usually strong solutions from which weaker ones may be made

conveniently. When correctly prepared, these solutions enable the pharmaceutical staff to

obtain small quantities of medicinal substances that are to be dispensed in solution.

Trituration

• Trituration is a method of diluting potent medicinal substances. These dilutions offer a

means of obtaining conveniently and accurately small quantities of potent drug for

compounding. Trituration may be done either manually in a mortar with a pestle or with a

mechanical device. Or

• Trituration referred to a pharmaceutical process of reducing substances to fine particles

through grinding in a mortar and pestle.

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 59

Alligation Medial

• Alligation medial is a method by which the „weighted average” percentage strength of

mixtures of two or more substances of known quantity and concentration may be quickly

calculated. The percentage strength expressed as a whole number, of each component of

the mixture is multiplied by its corresponding quantity and the sum of the products is

divided by the sum of quantities to give the percentage strength of the mixture, provided

of course that the quantities have been expressed in a common denomination whether of

weight or of volume

Alligation Alternate

• Alligation alternate is a method to calculate the number of parts of two or more

components of a given strength to prepare a mixture of required strength. The required

strength of the mixture to be prepared must lie somewhere between the strengths of its

components, i.e. the mixture must be stronger than its weakest component and weaker

than its strongest component. The amounts of components to be mixed are found by the

scheme as illustrated in the diagram of example number one.

STEP 3: Stock Solutions (20 Minutes)

• Stock solutions are invariably prepared on a weight in volume (w/v) basis and their

concentrations are expressed as ratio strength or less frequently, as percentage strength.

Examples

• How many milliliters of a 1:400 (w/v) of stock solution should be used to make 4 liters

of a 1:2000 (w/v) solution?

4L  4000mL

1 : 400  0.25%

Then, 0.25% 4000 mL

0.05% x mL

0.05  4000

x

0.25

x = 800mL Answer
CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

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• How many milliliters of a 1% stock solution of a certified red dye should be used in

preparing 4000mL of a mouth wash that is to contain 1:20000 (w/v) of certified red dye

as a coloring agent?

1 : 20000  0.005%

Then, 1% 4000mL

0.005% x mL

0.005  4000

x

1

x  20 mL, Answer
• What is the % strength of an ointment which contains 1.5 g benzoic acid in 30g of the

preparation? The answer is found as follows:

1.5 x

30 100

1.5  100

x  5%

30

The strength is 5% w/w, Answer.

STEP 4: Trituration, Alligation Medial and Alligation Alternate for Dilution

of Pharmaceutical Preparations (30 minutes)

Trituration

For example; in preparation of Antidandruff lotion, the following ingredients are used:

Salicylic acid……………………………………………………. 1.0 g
Cetrimide……………………………………………………….. 5.0 g
Liquid paraffin…………………………………………………. 3.0 mL
Alcohol (90%)………………………………………………….. 6.0 mL
Purified water…………………………………………………… to 100.0 mL

The 5g of Cetrimide is triturated with 3mL Liquid Paraffin; 1g of Salicylic Acid is

dissolved in 6mL of the Alcohol (90%), and added. The mixture is triturated well, water

is added to the required volume 100mL, and the preparation mixed.

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 61

Alligation Medial

• What is the percentage (v/v) of alcohol in a mixture of 3000mL of 40% (v/v) alcohol and
1000mL of 60% (v/v) alcohol and 1000 mL of 70% (v/v) alcohol (assume no contraction

in volume)?

40  3000  120000

60  1000  60000

70  1000  70000

5000 250000

250,000

Therefore,  50%

5,000

The percentage of alcohol in the mixture = 50% w/v. Answer.
• What is the percentage (v/v) of alcohol in a mixture containing 500mL of terpin hydrate

elixir 40% (v/v) alcohol, 400mL of theophylline sodium glycinate elixir 21% (v/v)

alcohol and sufficient simple syrup to make 1000mL?

40  500  20000

21  400  8400

0  10  0

Total 1000 28400

28400

Therefore  28.4%

1000

The percentage of alcohol in the mixture is 28.4% v/v, Answer.

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

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Alligation Alternate

• How many mL of 0.05% potassium permanganate solution must be added to 135 mL

potassium permanganate solution 1.5% in order to prepare a 0.5% potassium

permanganate solution?

Again the diagram is applied:

1.5 0.45 parts of 1.5% solution

0.5

1 parts of 0.05%

0.05 solution

As the amount of the 1.5% solution is already given, 0.45 part equals 135 mL and the

amount of 0.05% solutions is determined by the following proportion:

0.45 1

135 x

1  135

x  300mL

0.45

Therefore 300 mL potassium permanganate solution 0.05% is added to 135 mL

potassium permanganate solution 1.5% to produce a 0.5% solution, answer.

• Prepare 500 mL sodium chloride solution 0.9% by mixing a 2% and 0.5% sodium

chloride solution

2 0.4 parts of 2% solution

0.9

0.5 1.1 parts of 0.5%

solution

CMT 04101 Dispensing NTA L1.5 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 63

The sum of parts of the two components to be mixed is 1.5, which equal 500 mL. The
respective amounts of mL, which equal 0.4 part and 1.1 parts are again determined by

proportion:

1.5 0.4 0.4

 ,x   500  133.3mL of 2% solution, and

500 x 1.5

1.5 1.1 1.1

 , x  500  366.7 mL of 0.5% solution

500 x 1.5

Therefore, 133.3mL sodium chloride solution 2% is mixed with 366.7 mL sodium
chloride solution 0.5% in order to produce 500 mL 0.9% solution, Answer.

STEP 5: Dilution of Concentrated Solutions for External Use (45 minutes)

• Antiseptic: is a chemical agent used in antisepsis, a substance that opposes sepsis.
• Disinfectant: is a chemical agent used for disinfection.
• Disinfection: Is the destruction of micro-organisms, but not usually bacterial spores, it

does not necessarily kill all micro-organisms but reduces them to a level which is not

harmful. The term is applicable to the treatment of inanimate objects and materials.

Disinfection may also be applied to the treatment of the skin and other body membranes

and cavities.

• Antisepsis: Is the destruction or inhibition of microorganisms on living tissue having

effect of limiting or preventing the harmful results of infection.

• POTASSIUM PERMANGANATE

It possesses oxidizing (therefore disinfecting and deodorizing) and astringent properties.

Its bactericidal action is of short duration by its rapid reduction in the presence of body

fluids. It is incompatible with iodides, reducing agents and most organic substances.

Dilutions:

o 1: 10 000 to 1:5000 solution is used for urethral irrigations and as wet dressings

and baths in eczematous conditions and acute dermatoses, especially where

there is secondary infection

o 1:5000 solution is employed as a stomach wash-out in the treatment of

poisoning by morphine, opium and strychnine

o 1:4000 solution is used as gargle, mouth-wash, or vaginal irrigation

o 1:1000 solution is used as a cleansing application to ulcers and abscesses

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 64

o 1% solution has been used in bromhidrosis and in mycotic infections such as

athlete‟s foot

o 5% solution has a powerful styptic action

• PHENOL

It is a disinfectant effective against vegetative Gram-positive and Gram-negative bacteria,

but only very slowly effective against spores and acid-fast bacteria. It is also effective

against certain viruses. Its bactericidal effect is greatly weakened by dilution and by

blood and other organic matter. Phenol is more active in acid solution. Aqueous

solutions of 0.2 to 1% are bacteriostatic while stronger solutions are bactericidal. This

action varies with the organism, strength of solution and temperature.

Dilutions:

o 0.2 to 0.5% solution in glycerol is used as a mouth-wash or gargle

o 0.5 to 1% solution is used for its local anesthetic effect to relieve itching

o 2 % solution is used in small wounds dressing

o 5% solution may be used to devitalize the pulp in deciduous teeth

Precautions:

o Phenol and Liquefied Phenol BP are caustic to the skin.

Phenol splashes should be treated by rubbing the contaminated skin for at least 10

minutes with swabs soaked in glycerol. If this is not available, use water.

Alcohol and fixed oils provide relief as well.

o Phenol and Liquefied Phenol BP should be stored in airtight containers and

protected from light.

N.B:Carbolic Acid is a synonym for phenol. Liquefied Phenol BP contains 80% w/w of

phenol in water.

Refer students to Handout 10.1: Dilution of Concentrated Solutions for

further reading

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 65

STEP 6: Key Points (5 minutes)

Stock Solution

• Are solutions of known concentration that are frequently prepared for convenience in

dispensing. They are usually strong solutions from which weaker ones may be made

conveniently

Trituration

• Trituration method is applied when the medicament to be incorporated is insoluble in the

ointment basis or a liquid is present in a small amount. Solids are finely powdered in a

mortar and, if necessary, sifted. Add to the powders about two or three times their weight

of the basis or one of its ingredients, and triturate until a smooth mixture is obtained

• Trituration

For example; in preparation of Antidandruff lotion, the following ingredients are used:

Salicylic acid……………………………………………………. 1.0 g
Cetrimide……………………………………………………….. 5.0 g
Liquid paraffin…………………………………………………. 3.0 mL
Alcohol (90%)………………………………………………….. 6.0 mL
Purified water…………………………………………………… to 100.0 mL

The 5g of Cetrimide is triturated with 3mL Liquid Paraffin; 1g of Salicylic Acid is

dissolved in 6mL of alcohol (90%). The mixture is triturated well, water is added to the

required volume of 100mL, and the preparation mixed.

• Antiseptic: is a chemical agent used in antisepsis, a substance that opposes sepsis.
• Disinfectant: is a chemical agent used for disinfection.

Dilutions of Potassium Permanganate:

• 1: 10 000 to 1:5000 solution is used for urethral irrigations and as wet dressings and baths

in eczematous conditions and acute dermatoses, especially where there is secondary

infection

• 1:4000 solution is used as gargle, mouth-wash, or vaginal irrigation

Dilutions of Phenol:

• 0.2 to 0.5% solution in glycerol is used as a mouth-wash or gargle
• 0.5 to 1% solution is used for its local anesthetic effect to relieve itching
CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 66

STEP 7: Evaluation (5 minutes)

• What is allegation alternate, trituration, allegation medial and stock solution?
• What is stock solution?

STEP 8: Practice (20 hours)

• DIVIDE students in small manageable groups and conduct practices under facilitator‟s

supervision on the following.

o POTASSIUM PERMANGANATE GARGLE 1:4000

o COMPOUND SODIUM CHLORIDE MOUTH WASH BPC. 1973

o HYDROGEN PEROXIDE MOUTH-WASH PCx.

o ALKALINE PHENOL MOUTH-WASH PCx.

o HYDROGEN PEROXIDE EAR-DROPS PCx.

o SPIRIT WITH GLYCEROL AND ACETIC ACID EAR DROPS.

o CETRIMIDE SOLUTION PCx.

o CHLORINATED LIME AND BORIC ACID SOLUTION PCx. (Syn. Eusol)

o CRESOL AND SOAP SOLUTION B.P. 1968 (Syn. Lysol)

o WEAK IODINE SOLUTION PCx (Syn. Iodine Tincture)

Refer students to Worksheet 10.1: Practice on Compounding of Antiseptic

and disinfectant

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 67

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 Press.

Royal Pharmaceutical Society of Great Britain. (2007). Martindale : the complete drug reference

(S. C. Sweetman Ed. 35th ed.). London: Pharmaceutical Press.

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.

Stoklosa, M. J., & Ansel, H. C. (1996). Pharmaceutical calculations (10th ed.). Baltimore:

Williams & Wilkins.

Taber, C. W. (1997). Taber's cyclopedic medical dictionary (D. Venes Ed. 19th ed.).

Philadelphia, Pa.: F.A. Davis Co.,.

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 68

Handout 10.1: Dilution of Concentrated Solutions

Hydrogen Peroxide Solution

The following two solutions are contained in PCx.

Hydrogen Peroxide Solution: Is an aqueous solution containing about 6% w/v of hydrogen

peroxide, corresponding to about 20 times its volume of available oxygen.

Hydrogen Peroxide Solution, Dilute-an aqueous solution containing about 3% w/v of hydrogen

peroxide, corresponding to about 10 times its volume of available oxygen. The solution is

comparatively stable in the presence of a slight excess of acid but readily decomposes when

alkaline and when in contact with ox disable substances or certain metals. The addition of a

small amount of dilute phosphoric acid (10% w/w), dilute sulphuric acid (10% w/w), or benzoic

acid is therefore recommended. Hydrogen peroxide is used as a disinfectant and deodorant. It

owes its action to its ready release of oxygen when applied to tissues, but the effect is of short

duration. Solutions of hydrogen peroxide have poor powers of penetration and are

comparatively feeble disinfectants. They are of value for cleansing wounds; the effervescence of

oxygen detaches dead tissue and pockets of bacteria from inaccessible parts. Adhering and

blood soaked dressings are also removable with a solution of hydrogen peroxide. Discharging

ulcers, abscesses and venereal sores can be effectively cleansed.

CETRIMIDE

It is quaternary ammonium disinfectant effective against both Gram-positive and Gram-negative

organisms, but higher concentrations are necessary to kill the later type. It is relatively

ineffective against bacterial spores, acid fast bacteria, viruses and fungi. It is most effective in

neutral or slightly alkaline solution and its bactericidal activity is appreciably reduced in acid

media. It is incompatible with soaps and other anionic surfactants, bentonite, iodine, phenyl

mercuric nitrate, acid dyes and alkali hydroxides. For application to the skin, solutions

containing 0.1 to 1% of cetrimide are used. 0.5% solution in ethanol (70%) or isopropanol

(70%) is used for pre-operative skin disinfection after all traces of soap have been removed from

the skin. Solutions containing 1 to 3% of cetrimide are used as shampoos to remove the scales in

seborrhea and care should be taken to prevent the solution from entering the eyes. It may also be

used to prevent napkin rash. Baby napkins, after washing and thorough rinsing to remove soap

completely, are soaked in a weak solution of cetrimide and allowed to dry without rinsing.

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 69

Dilutions:

1: 200 SOLUTIONS:

• for general antiseptic purposes
• disinfections of hospital equipment
• rinsing instruments prior to sterilization
• disinfection of instruments (immerse for 30 minutes)
• storage of sterilized instruments

1:100 SOLUTIONS:

• swabbing in obstetrics
• disinfection of wounds and burns
• hand rinsing
• storage of thermometers

1:30 SOLUTION:

• cleansing and disinfecting dirty wounds and burns
• cleansing catheters and rubber appliance prior to sterilization

1:30 SOLUTION IN ETHANOL (70%) OR ISOPROPANOL (70%):

• emergency disinfection of instruments (immerse for 2 minutes)
• disinfection of clinical thermometers

Precautions:

o To prevent rusting; 0.4% of sodium nitrite should be added to solutions used to store

instruments

o Cetrimide is not a reliable agent for sterilizing surgical instruments and heat-liable

articles

o Cetrimide should not be applied repeatedly to the skin and wet dressings should not

be left in contact as hypersensitivity may occur

N.B: Savlon Hospital Concentrate® is a concentrated solution of cetrimide 15% and

chlorhexidine gluconate 1.5%.

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 70

Worksheet 10.1: Practice on Compounding of Antiseptic and disinfectant

Instructions: Under facilitator‟s supervision students in small manageable groups should practice on

preparing the following liquid preparations (antiseptic and Disinfectants), pack and label them ready

for dispensing.

The official formula for each preparations are obtained in Tanzania Pharmaceutical Handbook (TPH),

other Compedia may be used for more references

After compounding students will write a report on each preparation showing clearly the official

formula, all calculations performed, methods used for preparation, container used to pack, use of each

ingredient, and labels in English and in Swahili languages.

NOTE: For the preparations to be dispensed to patients should be attached with Swahili label and

preparations for Hospital or Laboratory use should be attached with English label

Questions / Instructions

1. Prepare 80 mL POTASSIUM PERMANGANATE GARGLE 1:4000 in water such that

when 2 teaspoonful of the solution are diluted with water by a patient to glass full capacity 250

ml will produce a Potassium Permanganate Gargle.

2. Prepare and dispense COMPOUND SODIUM CHLORIDE MOUTH WASH BPC. 1973. Sign:

10ml tds ×3/7

3. Prepare HYDROGEN PEROXIDE MOUTH-WASH PCx. Sign: 15 ml od ×2/7 for Uncle Kidevu
4. Prepare and dispense ALKALINE PHENOL MOUTH-WASH PCx. Sign: 10 mL nocte ×4/7 for

5. Prepare HYDROGEN PEROXIDE EAR-DROPS PCx. Sign: gtt ii a.u. tds ×5/7

6. Prepare SPIRIT WITH GLYCEROL AND ACETIC ACID EAR DROPS. Sign: gtt iii a.u. tds

×4/7

7. Prepare CETRIMIDE SOLUTION PCx. Mitte 40 mL fo Orthopedic ward. N.B. strong Cetrimide
Solution is o/s, therefore prepare Stock solution of 20 mL.
8. Prepare CHLORINATED LIME AND BORIC ACID SOLUTION PCx . Mitte 60 mL for

minor theatre.

9. Prepare CRESOL AND SOAP SOLUTION B.P. 1968. Mitte 50 mL for Microbiology

Laboratory

10. Prepare AQUEOUS IODINE SOLUTION PCx. Mitte 20 mL, Sign: gtt vi tds×3/52 for Mzee

Mpembuzi.

CMT 04101 Dispensing NTA L 4 Semester 1 Facilitator Guide

Session X: ———— -(Title)———————- 71

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