GMP Requirements on Raw Materials

Session 4: GMP Requirements on Raw Materials

Total Session Time: 120 minutes

Prerequisites

Learning Tasks

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

Resources Needed:

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

15 minutes Presentation Definition of Pharmaceutical Raw Material

2

50 minutes Types of Pharmaceutical Raw Materials Used

Presentation

3 in Pharmaceutical Manufacturing

discussion

30 minutes GMP Requirements for Pharmaceutical Raw

4 Presentation Materials

10 minutes Presentation

5 Key Points

6 10 minutes Presentation Evaluation

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

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 Pharmaceutical Raw Materials (15 minutes).

Pharmaceutical raw materials generally are substrates or elements which are used for

manufacturing different types of drugs, and basically categorized into three major types

which are:

Raw Material of API: Any substance or mixture of substances intended to be used in the

manufacture of a pharmaceutical dosage form and that, when so used, becomes an active

ingredient of that pharmaceutical dosage form. Such substances are intended to furnish

pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or

prevention of disease or to affect the structure and function of the body. Main thing is that

Accuracy and Precision are must for the raw materials which is used for making the API.

Raw Material of Expedients: is a substance formulated alongside the active ingredient of a

medication, included for the purpose of long-term stabilization, bulking up solid formulations

that contain potent active ingredients in small amounts (thus often referred to as "bulking

agents", "fillers", or "diluents"), or to confer a therapeutic enhancement on the active

ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or

enhancing solubility. Excipients can also be useful in the manufacturing process, to aid in the

handling of the active substance concerned such as by facilitating powder flowability or non-

stick properties, in addition to aiding in vitro stability such as prevention of denaturation or

aggregation over the expected shelf life. The selection of appropriate excipients also depends

upon the route of administration and the dosage form, as well as the active ingredient and

other factors

Raw Material of Packaging: Raw material which is used in making most of the packaging

involve plastic & polymers, glass, paper, aluminum foil and paper boards

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

STEP3:Types of Raw Materials Used in Pharmaceutical Manufacturing (50

minutes)

Activity: Small Group Discussion ( 10 minutes)

DIVIDE students into manageable groups

ASK students to discuss in groups on the following questions

ALLOW students to discuss for 5 minutes

ALLOW groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

The major types of raw materials used in pharmaceutical manufacturing are

pharmaceutical excipients commonly used in pharmaceutical manufacturing of solid

dosage forms.

TABLE ONE (1) EXCIPIENTS used in solid dosage forms.

Excipient Function in Working principle Examples

category formulation

Diluents Fillers Make up the bulk of solid Lactose, Directly

unit dosage forms when drug compressible

itself is inadequate to Starches, Dextrose,

produce the bulk Sorbitol,

Microcrystalline

cellulose, Dibasic

Calcium phosphate

Dehydrate

Binders and Impart cohesive Improves free flow Acacia, Gelatin, Starch

Adhesives qualities to powdered qualities by formulation of paste, Polyvinyl

material. granules to desired pyrrolidone, Glucose,

hardness and size Carboxymethyl

cellulose, Povidone

Lubricants Reduce inter-particular Interpose a film of low shear Talc, Stearic acid,

friction, prevent strength that interface Magnesium

adhesion of tablet between the tableting mass stearate, Calcium

material to the surface and die wall stearate, Polyethylene

of dies and punches glycol, Surfactants,

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

facilitate easy ejection vegetable oil

of tablet from die

cavity and improve the

rate of flow tablet

granulation

Glidants Improve flow Added in dry state prior Colloidal Silicone

characteristics of compression, it reduces dioxide

powder mixture friction between particles. (Carbosil), Asbestos free

starch, Corn starch

Disintergrants Facilitate breakup or Function by drawing water Starches, Clays,

disintegration into the tablet, swelling it Cellulose, Cross

after administration and causing the tablet to Linked polymers,

burst apart Modified starches such

as Primogel and

Explotab, Veegum HV.

Crosscarmalose, Cross

Povidone, Sodium starch

glycolate

Coloring Impart aesthetic FD and C, D and C dyes

agents ( these appearance to and lakes

must be dosage form, disguising

approved and off color drugs, product

certified ) identification

Flavors Limited to chewable Mask unpleasant taste Spray dried and other

tablets/ tablets flavors, syrups etc

Intended to dissolve in

mouth.

Sweeteners Impart sweet taste to Mannitol, Saccharin.etc

the formulation; use is

limited to chewable

tablets

Sorbents Moisture proofing Limits the fluid sorbing, Silica gel, activated

taking up of liquid or gas carbon, clay etc

either by adsorption or

absorption in dry state

Coating Protect tablet Hydroxypropylmethyl

materials ingredients from cellulose (HPMC),

deterioration by Synthetic polymers,

moisture, help Shellac, Corn protein

swallowing unpleasant Zein, Polysaccharides,

tasting tablets Capslues coated by

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Gelatin, Povidone, Ethyl

cellulose

Plasticizers For soft gelatin capsule Produce elasticity and Castor oil, Diacetylated

preparation, gelatin flexibility to the coating Monoglycerides,

based materials in case of tablets, Polyethylene glycol,

suppositories, film determine hardness of Polypropylene glycol,

coated capsule shell in Triacetin

tablets etc case of soft gelatin capsule

and impart softness and

resilience to suppositories

TABLE TWO (2) EXCIPIENTS USED IN LIQUID DOSAGE FORMS:

EXCIPIENT FUNCTION IN WORKING EXAMPLE

CATEGORY FORMULATION PRINCIPLE

Solvents. Dissolving Breaking of bonds Water, alcohol, acetic acid,

solute/Active and reducing acetone, ethyl

pharmaceutical effective charge acetates, syrups, etc

Ingredient. on ions thus

increasing Solute-

Co solvents Increase the solubility Solvent forces of

of solute in solvents attraction which

are eventually

greater than

Solute-Solute and

Solvent-Solvent

forces of attraction

Co-solvent system

works by reducing Ethanol, Sorbitol, Glycerin,

the interfacial Propylene glycol

tension between

predominantly

aqueous solutions

and hydrophobic

solutes

Buffers Maintain pH of the Act by binding Phosphate buffers, Acetate

Formulation hydrogen ions in buffers, Citric

acids and donating acid Phosphate buffers

hydrogen ions in

bases

Antimicrobial Prevent microbial Bacteriostatic Benzyl alcohol, Butyl

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Preservatives. growth in action paraben, Phenol,

formulations Thiomersal etc

Antioxidants. Control oxidation Act by getting Ascorbic acid, Sodium

preferentially bisulphate, Thiourea,

oxidized or by Butyl Hydroxy Toluene

blocking an (BHT),

oxidative chain Tocopherols.etc

reaction.

Wetting agents Aid wetting and Act by reducing Sodium Lauryl Sulphate

dispersion of interfacial tension (SLS), Tween 80, Spans,

hydrophobic active between solids Lecithins etc

pharmaceutical and liquids in

ingredients. suspensions

Antifoaming Discourage formation Lowers surface Simethicone, Organic

agents of stable foam. tension and phosphates, Alcohols,

cohesive binding Paraffin oils, Sterates and

of liquid phase glycols

Thickening Prevent Work by Methyl cellulose,

agents. settling/sedimentation, entrapment of Hydroxyethyl cellulose,

Modify viscosity. solid particles Microcrystallince cellulose

etc.

Humectants Retard evaporation of They are Propylene glycols, Glycerol,

aqueous vehicles from hygroscopic in Polyethylene glycol

dosage forms nature which helps

in preventing

evaporation of

solvent

Chelating agents Protect drug from Chelating agents Disodium EDTA, Dihydroxy

catalysts that form complexes ethyl glycine, Citric acid and

accelerate the with Tartaric acid

oxidative reaction metal ions

inactivating their

catalytic activity

in oxidation of

medicaments

Emulsifying Prevent coalescence Forms barriers at Sodium Lauryl Sulphate,

agents of the dispersed interface, and Cetrimide,

Globules. reduces interfacial Macrogol esters, Sorbitan

tension esters etc

Flocculating Prevent caking Addition of an Starch, Sodium alginate,

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

agents. electrolyte reduces Carbomer.etc

the magnitude of

zeta potential of

dispersed

particles.

Sweetening Impart sweetness Sucrose, Sorbitol, Saccharin,

agents Aspartame, Sucralase

Colors. Impart color Amaranth, Erythrosin, Eosin,

Tartarazine etc

Flavors Impart flavor Aromatic waters.

Excipient used in Developing pressure Trichloromonofluoromethane,

Aerosol in container which Dichlorodifluoromethane

Propellant expels the product

TABLE Three (3) EXCIPIENTS USED IN SEMI SOLID DOSAGE FORMS:

EXCIPIENT CATEGORY FX IN FORMULATION EXAMPLE

Structure forming Form gel like structure Cetosterly alcohol, sorbiton

excipients and other hydrophilic

surfactants , fluid

hydrocarbons like mineral

oils etc

Preservatives For preserving the Benzyl alcohol, proply

formulation paraben, methyl paraben,

chlorocresol, imidazolidinyl

urea, sodium benzoate

etc

Antioxidants Prevent oxidation Butyl hydroxy toulne , butyl

hydroxy anisole, ascorbic

acid etc

Solubilizers. Enhance solubility of the Lanolin, cholesterol or

active ingredient in ointments cholesterol esters

Gelling agents Form gels Carbomer934, pemulen®,

carboxy methyl cellulose,

hydroxy propyl cellulose,

xanthan gum etc

Emollients Modify vehicle/skin Glycerin, mineral oil,

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

characteristics to assist petrolatum, isopropyl

penetration of active palmitate etc

ingredient through skin

suppository bases Used to form base for Cocoa butter, glycerin,

dissolving coconut oil, gelatin,

active ingredient hydrogenated vegetable oil,

polyethylene glycol etc

STEP 4: GMP Requirements for Pharmaceutical Raw Materials (30

minutes)

General principle:

The main objective of a pharmaceutical plant is to produce finished products for patients‟ use

from a combination of materials (starting and packaging). Materials include starting

materials, packaging materials, gases, solvents, process aids, reagents and labeling materials.

Therefore the following should be taken into consideration, and that:

control, should come into direct contact with the product. Where possible, such materials

should be of a suitable grade (e.g. food grade) to minimize health risks.

receipt or processing and inspection, until they are released for use or distribution.

by the manufacturer and in an orderly manner to permit batch segregation and stock

rotation by First Expiry First Out and/or First In First Out rule.

of bin cards and stock cards or any fully validated electronic record system.

order to allow appropriate space for cleaning and inspection.

intended use.

STARTING MATERIAS.

has a particular and thorough knowledge of the products and suppliers.

directly from the producer. It is also recommended that the specifications established by

the manufacturer for the starting materials be discussed with the suppliers. It is of benefit

that all critical aspects of the production and control of the starting material in question,

including handling, labeling and packaging requirements as well as complaints and

rejection procedures, are contractually agreed between the manufacturer and the supplier.

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

and seal and for correspondence between the order, the delivery note, and the supplier‟s

labels.

the order. Containers should be cleaned where necessary and labeled, if required, with the

prescribed information. Where additional labels are attached to containers, the original

information should not be lost.

material should be recorded and reported to the quality control department and

investigated.

as separate for sampling, testing and release.

PACKAGING MATERIALS

as for starting materials.

in secure conditions so as to exclude the possibility of unauthorized access. Roll feed

labels should be used wherever possible. Cut labels and other loose printed materials

should be stored and transported in separate closed containers so as to avoid mix-ups.

Packaging materials should be issued for use only by designated personnel following an

approved and documented procedure.

specific reference number or identification mark.

be destroyed and its disposal recorded.

packaging department for quantity, identity and conformity with the packaging

instructions

FINISHED PRODUCTS

should be stored as usable stock under conditions established by the manufacturer.

product for sale are described under “Good practices in quality control”.

WASTE MATERIALS

disposal. Toxic substances and flammable materials should be stored in suitably designed,

separate and enclosed cupboards.

receptacles for removal to collection points outside the buildings and disposed of safely

and in a sanitary manner at regular and frequent intervals.

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

MISCELLANEOUS

permitted to contaminate equipment, starting materials, packaging materials, in process

materials or finished products.

STEP 5: Key points (10 minutes)

excipients and packaging materials.

manufacturing different types of drugs.

wetting agents etc

pharmaceutical dosage form and such substances are intended to furnish pharmacological

activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of

disease or to affect the structure and function of the body.

STEP 6: Evaluation (10 minutes)

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

Signore, A. A., & Jacobs, T. (2017). Good design practices for GMP pharmaceutical

facilities. Boca Raton, Fl.: CRC Press.

Lund, W. (2009). The pharmaceutical codex: Principles and practice of pharmaceutics. New

Delhi: CBS.

Aulton, M. E., & Taylor, K. (2018). Aulton s pharmaceutics: The design and manufacture of

medicines. Edinburgh: Elsevier.

Rawlins E.A, Editor: 1977 Bentley’s Textbook of Pharmaceutics, 8th Ed. Baillie're Tindall.

London

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PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

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