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Md. Imran Nur Manik Lecturer Department of Pharmacy Primeasia University

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Page 1: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Lecturer

Department of Pharmacy

Primeasia University

Page 2: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 1

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Introduction Pharmaceutical dosage forms contain both pharmacologically active compounds and excipients added

to aid the formulation and manufacture of the subsequent dosage form for administration to patients.

Definition The word excipient is derived from the Latin excipere, meaning 'to except', which is simply explained

as 'other than'. Pharmaceutical Excipients are substances other than the active medicament (s) which

are included in the manufacturing process or are contained in the finished pharmaceutical product

dosage form.

Role of excipients/Necessities of excipients/Purposes of excipients Excipient play a wide variety of functional roles in the pharmaceutical dosage form including

1. Modulating the solubility and bioavailability of the active pharmaceutical ingredients.

2. Modulating immunogenic response of active ingredients.

3. Maintaining the pH and /or osmolality of the liquid dosage form.

4. Improving dosing compliance (to give a particular shape and to improve palatability, elegance of

the formulation).

5. Increasing the stability of the active ingredient in the dosage form including protection from

degradation/ denaturation.

6. Preventing aggregation and dissociation of different molecules e.g. Protein and Polysaccharides.

7. Providing bulk to the formulation.

8. Helping the active ingredients to maintain preferable polymorphic form or conformation.

9. Conferring a therapeutic enhancement on the active ingredient in the final dosage form, such as

facilitating drug absorption, reducing viscosity, or enhancing solubility.

10. Aiding in handling of “API” during manufacturing. 11. Facilitating administration of the drug by the intended route.

12. Facilitating drug absorption or solubility and other pharmacokinetic considerations.

13. Ensuring a robust and reproducible physical product.

Classification of Excipients Excipients are classified by the functions they perform in the pharmaceutical dosage form. Principle

classes of the excipients are as follows.

1. Diluents (Bulking agents, Fillers)

2. Binder

3. Disintegrant

4. Lubricants

5. Glidant

6. Sweetening agents

7. Acidifying agents,

8. Air displacement agents,

9. Alkalizing agents,

10. Antifoaming agents,

11. Anti-microbial agents,

12. Preservatives,

13. Anti-oxidants,

14. Buffering agents,

15. Chelating agents,

16. Colors, complexing agents,

17. Emulsifying agents,

18. Flavouring agents and perfumes,

19. Humectants,

20. Ointment base,

21. Solvents & Co-Solvents,

22. Stiffening agents,

23. Wetting and solubilizing agents,

24. Viscosity imparting agent.

Page 3: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 2

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Properties of an ideal excipient

Excipients must have such quality that they will increase the stability of the product.

1. They should be compatible and have no interaction with the active ingredient in the preparation.

2. They must not adversely affect the product.

3. They should be pharmacologically inert.

4. They should be nontoxic, nonirritant in the concentration administered to the patient.

5. They should be nonvolatile.

6. They should be physically and chemically stable throughout the shelf life of the product.

7. They should be effective in low concentration over a wide range of pH.

8. They should be soluble in water as well as oil & fat.

9. They should be colorless, odorless and tasteless.

10. They should be cheap and readily available.

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.

Why excipients are important in a drug product?

Excipients are important for many reasons. Such as

1. It comprises the product delivery system i.e. transport the active drug at the site in the body

where the drug is intended to exert its action.

2. The excipients will keep the drug from being released too early in the assimilation process, in

the place where it can damage the tissue or can create gastric irritation or stomach upset. e.g

Diclophenac-Na (Coating is applied for this problem)

3. It helps the drug to disintegrate into particles small enough to reach the blood stream more

quickly. e.g. Disintegrating agents (Povidone).

4. Some of the excipients protect the stability of the product so that it will act with the maximum

effectiveness at the time of use. e.g. Stabilizers (Antioxidants ,Preservatives)

5. Some excipients aid in the identification of the product. e.g. Coloring & Flavoring agent

6. Some excipients are also simply used to make the product tasty and look better. This includes

patient‟s compliance especially in children. 7. In many product excipients makes up the total dosage form. e.g. Diluent.

Advantages and uses of excipients

The followings are important uses and advantages of excipients.

1. Excipients are used to give a particular size and shape of the medicaments. e.g.

Suppositories (Base).

2. To make the medication suitable for administration. e.g. Syrup, Suspension.

3. To protect the medication from gastric environment. e.g. Coating of tablet.

4. To mask unpleasant taste and odor. e.g. Sweetening agents & Flavoring agents.

5. To reduce the adhesion between powdered granules and punch face. e.g. Glidants.

6. To increase the stability of the product. e.g. Stabilizers.

7. To improve the appearance of the product. e.g. Coloring agents.

Page 4: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 3

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Stabilizers Stability: Stability of pharmaceutical product may be defined as the capability of a particular formulation

in a specific container &closure system to remain within the physical, chemical, microbiological,

therapeutic and toxicological specifications.

The substances which are used to control these stabilities are known as stabilizers.

The most important stabilizers are,

1. Antioxidants and

2. Preservatives.

Antioxidant An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Antioxidant added

to pharmaceutical formulation to prevent the oxidative degradation of the drug in the presence of

oxygen or peroxides.

They act by blocking an oxidative chain reaction. The antioxidants have great affinity for oxygen and

when they are added to formulation they compete for it affording protection to other oxygen sensitive

drugs.

Some antioxidants are:

1. Quinol group

Hydroquinone

Tocopherols

Hydroxychromans

2. Catechol group

Catechol

Pyrogallol

Gallic Acid

Ethyl Gallate

3. Nitrogen containing Substance

Alkanolamine

Diphenylamines

Casein

Edestine

4. Sulphur containing Substance

Cysteine Hydrochloride

5. Monohydric Phenol

Thymol

Classification of antioxidant

1. On the basis of the function antioxidants are two types. They are,

a. Primary antioxidants/ true antioxidants.

b. Synergists.

Primary antioxidant: Primary antioxidants or true antioxidant act by breaking the antioxidant chain

usually by interfering with the propagation step of autoxidation process.

e.g., Tocopherol (Vitamin E), Gallic acid, Butylated hydroxyl anisol (BHA), Butylated hydroxyl tolune

(BHT) and nordihydroguaiaretic acid (NDGA).

Synergist: The synergist class of antioxidants has little inherent anti-oxidation properties. They act by

enhancing the action of true antioxidants usually by regenerating them or by removing pro-oxidant trace

metals known to catalyse the oxidative degradation.

e.g. EDTA and its Ca & Na salt, Citric acid, Glycerine, Propylene glycol, Polyethylene glycol etc.

2. On the basis of solubility antioxidants are two types. They are,

a. Water soluble antioxidant.

b. Oil soluble antioxidant.

Page 5: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 4

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Water soluble antioxidant: The main classes of water soluble antioxidants are sulfurous acid salts,

ascorbic acid isomers and thiol derivatives.

The important characteristics, storage condition and uses of members of this class are tabulated below.

Compound Solubility pH Drugs for which suitable Conc. Storage

Sodium

bisulfite

Soluble in water,

slightly soluble in

alcohol.

1-5 Steriods, antibiotics,

adrenergics,procainamide,

dextrose morphine

0.05%

Away from

light, Below

40◦C

Sodium

metabisulfite

Soluble in water,

slightly soluble in

alcohol.

acidic epinephrine

0.025-0.1%

Away from

light, Below

40◦C

L-Ascorbic

acid

Soluble in water

and alcohol

3-6 Epinephrine, Ferrous

sulfate

0.2-0.5%

Air tight,

away from

light.

Thioglycerol

Slightly soluble in

water, miscible with

alcohol

3.5-7 Streptomycin sulphate,

reserpine, Methyl-dopa,

promethazine

0.1-0.5%

Air tight,

cool place

Oil soluble antioxidant: The oil soluble antioxidants are often needed for the protection of fatly foods

and cosmetics. In the pharmaceutical field, formulations like ointments, oily injections etc. containing g

oxygen sensitive drugs may require protection by anti-oxidants.

Some of the oil soluble antioxidant properties are given below.

Compound Solubility Materials for

which suitable

Conc. Storage

Butylated hydroxyanisol (BHA)

& Butylated hydroxytoluene

(BHT)

Soluble in alcohol,

propylene glycol

Fatty

formulations

0.005-0.02% Normal

condition

Propyl gallate Soluble in alcohol,

slightly soluble in water.

Thiothixene 0.01-0.1% Normal

condition

Tocopherols Soluble in alcohol Vitamin A 0.05-0.75% Air tight,

away from

light.

Properties of Antioxidants (Choice of antioxidants)

An antioxidants in addition to their antioxidative properties must possess certain other desirable features

indicated below for use in the pharmaceutical preparation.

1. Ought to dissolve readily in the substrate.

2. It should be nontoxic and free from irritant and sensitizing qualities.

3. Must not interfere with the organoleptic properties of the product.

4. It should be compatible with formulation ingredients and packaging material.

5. Should be thermo stable and effective against a wide range of pH.

6. Effective at a low concentration.

7. It should not possess objectionable color, odor and taste.

8. Reasonable cost.

Page 6: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 5

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Some commonly used drugs sensitive to oxidation

Drugs that are sensitive to oxidation are, 1. Ascorbic acid (Vitamin C)

2. Chlorpromazine.

3. Cyanocobalamine (Vitamin B12)

4. Gentamicin.

5. Heparin.

6. Hydrocortisone.

7. Resorcinol.

8. Riboflavin (Vitamin E)

9. Streptomycine.

10. Methyldopa.

11. Morphine.

12. Penicillin.

13. Tetracycline.

14. Thiamine (Vitamin B1)

15. Vitamin A,D and E

16. Paracetamol

Preservatives

Most pharmaceutical formulations are liable to microbial growth and therefor have to be properly

preserved.

A preservative is a substance which is added to pharmaceutical formulation to prevent or inhibit the

growth of microorganisms in the preparations in order to prolong their shelf life.

Preservatives are used in multi-use cosmetic/pharmaceutical products (including paediatric formulations)

to prevent an increased risk of contamination and proliferation by opportunistic microbes (from

excipients or introduced externally), that would result in potential health issues.

Ideal properties of preservatives

In concept, the preservative system protects the product against microbial proliferation but does not

compromise product performance. In practice, the preservative selected should have the following

properties.

1. Exert a wide spectrum of antimicrobial activity at low inclusion levels.

2. Maintain activity throughout product manufacture, shelf life and usage.

3. Not compromise the quality or performance of product, pack or delivery system.

4. Not adversely affect patient safety or tolerance of the product.

5. It should be chemically compatible with other ingredients of the formulation.

6. It should be nontoxic and non-sensitizing.

7. It should be soluble in aqueous phase when used in emulsions.

8. It should be odourless, tasteless, and should not impart colour in the formulation.

9. It should be stable and effective over a wide range of pH.

10. It should be of low volatility to ensure that loss does not occur during storage.

Examples: Methyl paraben and Propyl paraben 0.1-0.2%,

Ethyl parabens, Propylparaben, Butylparaben,

Benzoic acid and benzoates 0.1-0.2%,

Sorbic acid and its salts 0.05-0.2%,

Alcohol 15-20%,

Benzalkonium chloride 0.004-0.02%,

Phenol 0.2-0.5%.

Page 7: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 6

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Q. Define combine preservative. Why more than one preservative are used in pharmaceutical

formulation?

The use of two or more preservative collectively known as combine preservative.

No single preservative possesses all the ideal properties. Sometime a single preservative is not enough

or not have the ability to kill or inhibit the growth of microorganism. Therefore it becomes necessary to

use a combination of preservatives to prevent the growth of microorganisms. These days a combination

of two or more preservatives is more in fashion, because such combinations give a broader spectrum of

anti-microbial qualities.

e.g., 0.1- 0.2% Methyl paraben and Propyl paraben which are oil and water soluble respectively used

due to their synergist effect in combined form.

Some Specific Preservatives Benzoic acid and benzoates

1. Simple aromatic acid.

2. Use as a preservative for food, drug, cosmetics etc.

3. Concentration 0.1%.

Parahydroxybenzoates

1. Use for the preservation of food and drug.

2. Various ester of p-hydroxy benzoic acid having methyl, ethyl propyl and butyl radicals are marketed

by different forms under names such as Nipase ceries paraben etc.

3. Concentration 0.005-0.05%

4. Powerful preservative.

5. The esters are considered to be 2-3 times effective as benzoic acid.

6. The different ester may have different action against different classes of microbes. For instance, a

methyl ester is considered to be more effective against mould. Propyl ester is so against yeasts.

Phenyl mercuric nitrate & other salt

1. Low concentration as 1 in 1,00,000.

2. Use for cosmetic.

3. It is recognized preservatives of pharmaceutical product for parental use.

Phenol

1. Classical germicide.

2. Use in lotion and other preparation for internal use.

3. Used in particular products packed as multiple doses in concentration of 0.5%

Dichlorophen

1. Fungicide and bactericide.

2. Use for preservation of natural fiber like cotton and wool.

3. Use as an ingredient for hair tonic and athletes.

4. It is rather tonic and not use in pharmaceutical preparation as preservatives.

Formaldehyde

1. Good preservatives for different kind of material.

2. It is not use in pharmaceutical preparation as preservatives.

3. Is has strong pungent and irritant properties.

Page 8: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 7

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Mode of Action Preservatives interfere with microbial growth, multiplication, and metabolism through one or more of

the following mechanisms

• Modify cation of cell membrane permeability and leakage of cell constituents (partial lysis) • Lysis and cytoplasmic leakage

• Irreversible coagulation of cytoplasmic constituents (e.g., protein precipitation)

• Inhibition of cellular metabolism, such as by interfering with enzyme systems or inhibition of cell wall synthesis

• Oxidation of cellular constituents • Hydrolysis A few of the commonly used pharmaceutical preservatives and their probable modes of action are

presented in following Table

Preservative Probable modes of action

Benzoic acid, boric acid,

p-hydroxybenzoates

Denaturation of proteins

Phenols and chlorinated phenolic compounds Lytic and denaturation action on cytoplasmic membranes and

for chlorinated preservatives, also by oxidation of enzymes

Alcohols Lytic and denaturation action on membranes

Quaternary compounds Lytic action on membranes

Mercurials Denaturation of enzymes by combining with thiol (-SH) groups)

Ointment Bases Ointments are greasy, semisolid preparations, often anhydrous and containing dissolved or dispersed

medicaments.

The ointment base is that substance or part of an ointment, which serves as a carrier or vehicle for the

medicament.

Properties of an ideal ointment base An ideal ointment based should have the following criteria.

1. It should be inert.

2. It should be stable.

3. It should be smooth.

4. It should be compatible with the skin.

5. It should be non-toxic, non-irritating and nonvolatile.

7. It should have low melting point.

8. It should release the incorporated medicament readily.

Since there is no single ointment base available which possesses all these qualities, therefore it becomes

necessary to use more than one ointment base in the preparation of ointments.

Classification of ointment base

The ointment bases are classified as follows:

1. Oleaginous bases or fatty bases

2. Absorption bases

3. Emulsion bases

4. Water soluble bases.

1. Oleaginous Bases: These bases consist of water insoluble hydrophobic substances e.g. oils and fats.

The most important are the hydrocarbons. i.e. mineral oil, petrolatums and paraffins. The animal fat

includes lard. The combination of these materials can produce a product having desired melting point

and viscosity.

Page 9: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 8

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

The oleaginous bases are decreasing in favour due to the reasons described below. 1. They are greasy. 2. They are difficult to remove both from skin and clothings. 3. The release of medicament is not certain. 4. If some animal fat is included it may get rancid. 5. Fatty mixture bases prevent drainage on oozing areas and also prevent evaporation of cutaneous secretions including perspiration. The water retention increases the heat in the particular areas.

Hydrocarbon Bases

I. Petrolatum (Soft Paraffin): It is a purified mixture of semisolid hydrocarbons obtained from petroleum.

There are two varieties of soft paraffin, one is yellow soft paraffin and the other is white soft paraffin.

Yellow soft paraffin is a pale yellow to yellow translucent soft mass, free or almost free from odour and taste. It has a melting point of 38°C to 56°C. White soft paraffin is obtained by bleaching yellow soft paraffin. It is a white translucent tasteless mass and is odourless when rubbed on the skin. It has a melting point of 38°C to 56°C. White soft paraffin is used when the medicament is while or colourless. Both yellow and white soft paraffins are used and have no noticeable action on the skin and are not absorbed. Thus they are suitable for epidermal type of preparations. Because of hydrophobic nature, aqueous liquids cannot be mixed with it but sometimes wool fat and waxes are included to incorporate aqueous liquids in it.

II. Hard Paraffin: It is a purified mixture of solid hydrocarbons obtained by distillation from petroleum or

shale oil. It is a colourless or white translucent, odourless, tasteless mass and is used to harden or stiffen

the ointment bases.

III. Liquid Paraffin: It is also known as liquid petrolatum or white mineral oil. It consists of a mixture of

liquid hydrocarbons and may be obtained from petroleum by distillation.

Liquid paraffin varies in composition according to the source of the petroleum. It is a colourless, transparent, tasteless and odourless oily liquid. It is insoluble in water and alcohol but soluble in ether and chloroform. It is used along with hard paraffin and soft paraffin to get a desired consistency of the ointment. It is also used to levigate the substances insoluble in it.

2. Absorption base

The term absorption is used to denote the hydrophilic characters of the base. These are generally

anhydrous bases which can absorb a large amount of water but still retain their ointment like

consistency. Generally, they are anhydrous vehicles composed of a hydrocarbon base and a miscible substance with polar groups that functions as a water-in-oil emulsifier, e.g. lanolin, lanolin isolates, cholesterol, lanosterol and other sterols, acetylated sterols, or the partial esters of polyhydric alcohols such as sorbitan monostearate or mono-oleate.

The following are some of the absorption bases used.

A. Wool Fat: It is also known as anhydrous lanolin. It is the purified anhydrous fat like substance

obtained from the wool of sheep. It is practically insoluble in water but can absorb about 50% of its

weight of water. Due to its sticky nature it is not used alone but is used along with other bases in the

preparation of a number of ointments.

B. Hydrous Wool Fat: It is also known as lanolin. It is the purified fat like substance obtained from wool

of sheep. It is a yellowish white ointment like mass with characteristic odour. It is insoluble in water but

soluble in ether and chloroform.

Page 10: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 9

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

C. Wool Alcohol: It is obtained from wool fat by treating it with alkali and separating the fraction

containing cholesterol and other alcohols. It contains not less than 30% of cholesterol. It is used as an

emulsifying agent for the preparation of water in oil emulsions and is used to absorb water in ointment

bases. It is also used to improve the texture, stability and emollient properties of oil in water emulsions.

D. Bees Wax: It is purified wax obtained from the honeycomb of bees. It is of two types: (a) yellow bees

wax and (b) white bees wax obtained by bleaching and purifying the yellow bees wax. Bees wax is used

as a stiffening agent in pastes, ointments and other preparations.

E. Cholesterol: It is widely distributed in animal organisms. Wool fat is also used as a source of

cholesterol. It is used to increase the incorporation of aqueous substances in oils and fats.

Advantages of Absorption Bases 1. They are compatible with majority of medicaments. 2. They are relatively heat stable. 3. These bases may be used in their anhydrous form or in emulsified form. 4. They can absorb a large quantity of water or aqueous substances. 5. They can be more easily removed from the skin in compared to the oily bases. Disadvantage of Absorption Bases 1. These bases possess the undesirable property of greasiness.

3. Emulsion Bases

Emulsion bases are semi solid emulsions having cream like consistency. These are of two types: oil in

water or water in oil emulsions. Examples of emulsion bases include hydrophilic ointment, rose water

ointment and vanishing creams.

Some additional amount of water can be incorporated in both the types and still retain soft cream like consistency. The oil in water type emulsion bases are more popular because they can be easily removed from the skin or clothings by washing with water. The water in oil emulsion bases are greasy and sticky, therefore they are difficult to remove from the body and clothings. Examples of emulsion bases include hydrophilic ointment, rose water ointment and vanishing creams. 4. Water Soluble Bases

Water soluble bases contain only the water soluble ingredients and not the fats or other greasy

substances that is why sometimes they are known as greaseless bases. They differ from emulsion bases

that the latter contain water soluble and water insoluble components. Since these bases do not contain ally fats or oils, they can be easily washed with water from the skin and clothings. Certain other substances which are used as water soluble bases include tragacanth, gelatin, pectin, silica gel, sodium alginate, cellulose derivatives, magnesiutn-aluminium silicate and bentonite. In the true sense these substances are not water soluble but they swell up with the absorption of water.

Surfactants

Surfactants or surface active agents are the substances which when added to a liquid that lower the

surface tension (or interfacial tension) between two liquids or between a liquid and a solid and increase

the solubility. For e.g. Surfactants decrease the surface tension of a material, coating agent, and a substrate, a tablet. By reducing the surface tension, the coating can more uniformly cover the tablet surface, resulting in a more aesthetically pleasing product. When used in suspension, the surfactant facilitates the wetting of the drug particle, facilitating its ability to go into solution. They may be used as emulsifying agents, detergents, solubilising agents, wetting agents, foaming agents.

antifoarning agents, flocculating agents and deflocculating agents.

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Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 10

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Properties of surfactants: A surfactant must fulfil two structural requirements-

a) A surfactant must contain a lipophilic region.

b) A surfactant must contain a hydrophilic region.

In a surfactant both hydrophilic and lipophilic region must be balanced because then both the regions

will be concentrated at an interface and therefore surface tension will be lowered.

Types of surfactants

Surfactants can be classified in a number of ways but the most widely acceptable classification system is

based on ionic behaviour in the solutions.

There are of four types of surfactants based on the charge of the hydrophilic region.

1. Anionic surfactant (here the hydrophilic region is negatively charged i.e. an anion): They ionise in

aqueous solutions into a large anion. e.g. Sodium lauryl sulphate - It is used as an excipient on some

dissolvable aspirins and other fibre therapy caplets.

2. Cationic surfactant (here hydrophilic region is positively charged i.e. a cation): They ionise in aqueous

solutions into a large cation. e.g. Cetyl trimethyl ammonium bromide (cetrimide) - is an effective

antiseptic agent against bacteria and fungi.

3. Non-ionic surfactants : They do not ionise in aqueous solution.

e.g. Tween 80 ( polyoxyethylene sorbitol monooleate)- Polysorbate 80 is an excipient that is used to

stabilize aqueous formulations of medications for parenteral administration

Span (sorbitan ester of lauric acid)

4. Amphoteric surfactant: e.g. Lecithin- it acts as a wetting, stabilizing agent and a choline enrichment

carrier, helps in emulsifications and encapsulation, and is a good dispersing agent. N-dodecyl alanine.

Figure: Different types

of micelles.

(A) Spherical micelle of

an anionic surfactant;

(B) spherical micelle of

a nonionic surfactant;

(C) cylindrical micelle of

an ionic surfactant;

(D) lamellar micelle of

an ionic surfactant;

(E) reverse micelle of an

anionic surfactant in

oil. (From Shinoda K,

Nakagawa T, Tamamushi B-I,

Isemura T. Colloidal Surfactants. New

York: Academic Press, 1963.)

Page 12: Pharmaceutical excipients-MANIK

Md. Imran Nur Manik

Md. Imran Nur Manik

Pharmaceutical Excipients

Prepared By: Md. Imran Nur Manik; M.Pharm. (R.U.) Page 11

[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

The mechanism action of surfactant The molecules of a surfactant consist of two parts, i.e. a polar part and non-polar part. When such

molecules are placed in two phases of different polarities the polar part moves towards high polarity

phase while non-polar part moves towards the low polarity phase and preferentially they are absorbed

at the interphase. As the concentration is increased a level is reached where the interphase becomes

saturated with surface active agents and no more space is available at the surface to be occupied.

Therefore the surfactant molecules move towards the bulk of the solution. At this concentration an

unusual phenomenon occurs. The molecules tend to form colloidal aggregates known as micelles

consisting of 50 to 150 molecules of surface active agents. The concentration of surfactant at which the

micelles are formed is known as critical micelle concentration or C.M.C. The solubilization begins at

C.M.C and generally increases with increase the concentration of micelles.

Micelle: The colloidal aggregate molecules consisting of 50 to 150 molecules of surface active agents known as micelles. C.M.C: The concentration of surfactant at which the micelles are formed is known as critical micelle concentration or C.M.C.

Emulsifying agents (Emulgents or Emulsifier) Emulsifying agents are those substances used in the emulsion to reduce the interfacial tension between

the two phases i.e. aqueous phase and oily phase thus make them miscible with each other to form a

stable emulsion.

Classification Emulsifying agents may be classified as follows:

1. Natural emulsifying agents from vegetable origin

The natural emulsifying agents obtained from vegetable sources are carbohydrates which include gums and

mucilaginous substances. They are anionic in nature and produce O/W emulsion. Examples are

a. Acacia

b. Tragacanth

c. Agar

d. Chondrus (Irish moss0

e. Pectin

f. Starch.

2. Natural emulsifying agents from animal origin

Examples are

a. Gelatin

b. Egg yolk

c. Wool fat (Anhydrous lanolin)

3. Semi-Synthetic polysaccharides

Examples are

a. Methyl Cellulose

b. Sodium carboxymetjhyl cellulose

4. Synthetic emulsifying agents

This group includes surface active agents.Examples are

a. Anionic: Various alkali soaps, metallic soaps, sulphated alcohols and sulphonates.

b. Cationic: Quaternary ammonium compounds.

c. Non-ionic: Glyceryl esters e.g. Glyceryl monostearate.

5. Inorganic emulsifying agents

Examples are

a. Magnesium oxide

b. Magnesium trisilicate

c. Magnesium aluminium silicatwe

d. Bentonite

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6. Alcohols

Examples are

a. Cholesterol

b. Carbowaxes

The choice of emulsifying agents To get an emulsion of required properties, the emulsifying agent selected must have the following qualities.

1. It should be capable of reducing the interfacial tension between the two immiscible liquids.

2. It should be capable of keeping the globules of dispersed liquid distributed indefinitely throughout the

dispersion medium.

3. It should be non-toxic,

4. The odour and taste should be compatible with the preparation.

5. It should be chemically compatible with other ingredients of the preparation.

6. It should be able to produce and maintain the required consistency of the preparation.

Organoleptic Additives

Organoleptic properties are those which can be sensed with organs. In case of pharmaceutical

preparations ,three of these properties can be changed to make a pharmaceutical product more

palatable and more attractive, especially for liquid dosage forms.

These are i. Color ii. Odor and iii. Taste

Colors

Colouring agents may be defined as the substances used to impart colour to foods, drugs and cosmetics

to increase their organoleptic properties. In the pharmaceutical products Colouring agents impart the

preferred colour to the formulation. The function of these ingredients is to enhance the product quality.

They are used for

1. Product identification.

2. Increasing product acceptability to the patients.

3. Giving warning.

4. Producing standard preparations.

Sources Colours may be obtained from

1. Mineral: Colours obtained from minerals are also known as pigments. e.g. ferric oxide (yellow

and red), carbon black, titanium di oxide, Prussian blue etc.

2. Plants: Different colours obtained from plants. e.g. Chlorophyll, indigo, alizarin, carotenoids,

flavones etc.

3. Animal: The animal world has been comparatively a minor source of colours. e.g. Tyrian blue,

Cochineal etc.

4. Synthetic: The synthetic colours are prepared from coal tar dyes. e.g. nitro-dyes, nitroso-dyes,

azo-dyes, thiazines etc.

They are either soluble or form fine suspension in the solvent system. For uniform distribution the

particle size must be < 10 microns. If a very light shade is desired a concentration is less than 0.01%.

On the other hand if dark colour is required concentration is more than 2%.

Example: White: Titanium dioxide

Blue : Brilliant blue ,Indigo carmine

Red : Amaranth Carmine

Yellow: saffron

Brown: caramel

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Flavouring agents and perfumes Flavouring agents are the substances which are used to impart pleasant smell to the preparation and to

mask specific type of taste of the preparation, thus make them more palatable and improve patient

acceptance.

The four basic taste sensations are salty, sweet, bitter and sour. It has been proposed that certain

flavours should be used to mask these specific taste sensations.

Example: Clove oil, citric and syrup, glycerin, rose oil, orange oil, raspberry flavor, vanilla flavor etc.

Classification flavouring agents

1. Natural flavouring agent: The flavouring agents obtained from natural sources include pine-apple,

banana, cardamom, ginger, cinnamom, peppermint and volatile oils obtained from anise, caraway

clove, dill, lemon oil, orange, rose, jasmine, lavender etc. Malt extract, glycyrrhizin extract, coffee,

vanilla, chocolate and tolu balsam are also used as flavouring agents. Menthol, mannitol, chloroform

spirit and chloroform water are widely used as flavouring agents in liquid formulations.

2. Synthetic colouring agent: Synthetic chemical like certain alcohol, aldehydes, esters, fatly acids,

ketones and lactones are used as flavouring agents. More recent butterscotch, „tutti-frutti‟ flavor are used.

Q. Why synthetic flavouring agents are better than natural flavouring agents. Most of the flavours used in pharmaceutical preparations are obtained from natural sources but now a day they are being replaced by synthetic flavours. This is due to, 1. They are constant in composition. 2. They are readily available. 3. They are comparatively cheap. 4. They are more stable. 5. Their incompatibilities are more predictable.

Relation between taste and flavour There is a close relation between taste and flavour. In case of pharmaceutical p[reparations the

following guidelines should be followed.

Matches between taste and flavours

Taste Flavour/Flavours

Alkaline Mint, Chocolate, vanilla, custard

Acid (Sour) Lemon, orange, raspberry, cherry, strawberry

Bitter Anise, mint, fennel, chocolate, spicy ,cherry

Metallic Grape, lemon, burgundy

Salty Citrus flavour, maple, raspberry, fruity, melon

Sweet Fruity, vanilla, maple, honey

Matches between flavours and colours

Flavours Colures

Cherry, raspberry, strawberry, apple, rose Pink, red

Chocolate, honey, molasses, caramel Brown

Lemon, lime, orange, Cherry Yellow to orange

Banana, mint,, pistachio Green

Vanilla, mint, spearmint, jasmine, banana White to off white

Grape, liquorice Violet to purple

Blue berry, mixed fruit, plum, liquorice blue

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In general, children like very sweet flavours and so do the people in the geriatric group. Children prefer

cherry, grape, orange etc., while the old persons may prefer flavours like orange, cherry, burgundy etc.

Adult preferences are vanilla, strawberry, mint etc. Very strong flavours as a rule should be avoided.

Sweetening agents Sweetening agents are the substances which are used in the formulations to mask the objectionable

taste of the drug and to make the preparations sweet in taste.

Sweetening agents are usually employed in the liquid formulations designed for oral administration

specifically to increase the palatability of the therapeutic agent.

Example: Sucrose, Lactose, Aspartame, Sorbitol, Mannitol etc.

The main sweetening agents employed in oral preparations are sucrose, liquid glucose, glycerol,

sorbitol, saccharin sodium and aspartame. Aspartame is an artificial sweetening agent. The use of

artificial sweetening agents in formulations is increasing.

The use of sugars in oral formulations for children and patients with diabetes mellitus is to be avoided. Why mannitol is extensively used in chewable tablets Chewable tablets are intended to be chewed in the mouth prior to swallowing and are not intended to be swallowed intact. The use of sweeteners is primarily limited to the chewable tablets to exclude or limit the use of sugar in the tablet. Sucrose causes hyperglycaemia. So we have to exclude it in the chewable tablet. Saccharine can use in place of sucrose, but it has the disadvantage that it has a bitter after taste and has been reported to be carcinogenic. Aspartame can be used in place of saccharine, but the primary disadvantage of aspartame is its lack of stability in the presence of moisture. For the above reason mannitol is used extensively in the chewable tablet because- a. Mannitol is reportedly about 72% as sweet as sucrose. b. It does not have bitter after taste. c. It has the stability in the presence of moisture. d. It does not produce hyperglycaemia.

Acidifying agents Acidifying agents are the substances that are used in liquid preparation to provide acidic media for

product stability.

e.g. Citric acid , Acetic acid, Fumaric acid, Hydrochloric acid, Nitric acid .

Air displacement agents Air displacement agents are the substances employed to displace air in a hermetically sealed container

to enhance product stability. e.g. nitrogen. carbon dioxide.

Alkalizing agents Alkalinizing agents are the substances which provides alkaline medium for product stability in liquid

preparations. Alklinizing agent excipients are important in pharmaceutical formulations where the active

pharmaceutical ingredient requires an alkaline environment for stability or therapeutic effectiveness.

e.g. Ammonia solution, Ammonium carbonate, Diethanolamine, Monoethanolamine,

Potassium hydroxide, Sodium bicarbonate, Sodium borate, Sodium carbonate, Sodium hydroxide

Trolamine , Sodium citrate/citric acid, Sodium lactate Alkaline agents are used to balance the acids of our body and to strengthen the effect of cleaning solutions. Maintaining a proper potential hydrogen (pH) level is vital to our health, keeping cholesterol, blood sugar and the heart's circular system running smoothly. If pH level is kept at 7, the alkaline and acids are equally balanced, influencing bone health, proper digestion, electrolyte activity and keeping immunity strong to prevent sickness.

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[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Anti-Foaming Agent A defoamer or an anti-foaming agent is a chemical additive that breaks up and inhibits the formation of

foams in liquids by reducing interfacial tension between two phases. In pharmaceutical industry defoamers

are used as to reduce bloating (ফীহতা )

A familiar example is the drug Simethicone which is the active ingredient in drugs such as Entacyd plus.

Others include: Dimethicone, Lauric acid NF32, Myristic acid

Palmitic acid.

Properties of an anti-foaming agent 1. It should be insoluble in the foaming medium.

2. It should be surface active.

3. Should have low viscosity.

4. It should spread rapidly on foamy surfaces.

5. It has affinity to the air-liquid surface where it destabilizes the foam lamellas.

Classification

Anti-foaming agents are classified into the following types.

1. Oil based anti-foaming agents: Oil based anti-foaming agents have an oil carrier. Oil and water do

not mix with each other so these are the best anti foaming agents. The oil might be mineral oil,

vegetable oil, white oil or any other oil that is insoluble in the foaming medium except silicone oil. An oil based defoamer also contains a wax and/or hydrophobic silica to boost the performance. Typical waxes are ethylene bis stearamide (EBS), paraffin waxes, ester waxes and fatty alcohol waxes. These products might also have surfactants to improve emulsification and spreading in the foaming medium.

2. Powder anti-foaming agents: Powder anti-foaming agents are in principle oil based defoamers on a

particulate carrier like silica. These are added to powdered products like cement, plaster and detergents.

3. Water based anti-foaming agents: Water based anti-foaming agents are different types of oils and

waxes dispersed in a water base.

The oils are often white oils or vegetable oils and the waxes are long chain fatty alcohol, fatty acid soaps or esters. These are normally best as deaerator, which means they are best at releasing entrained air. 4. Silicone based anti-foaming agents: Silicone-based anti-foaming agents are polymers with silicon

backbones. These might be delivered as oil or a water based emulsion.

The silicone compound consists of hydrophobic silica dispersed in silicone oil. Emulsifiers are added to ensure that the silicone spreads fast and well in the foaming medium. The silicone compound might also contain silicone glycols and other modified silicone fluids.

Buffering agents A buffering agent adjusts the pH of a solution. These materials, when dissolved in solvent enable the

solution to resist any change in pH. They are added to substances that are to be placed into acidic or

basic conditions in order to stabilize the substance.

Change in the pH of preparation may occur during storage because of degradative reaction in the

product or by the Interaction of the product with container.

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So, buffers are used to maintain a required pH of the formulation in order to:

Ensure physiological compatibility

Maintaining/optimising chemical stability

Maintaining/optimising anti-microbial effectiveness

Optimise solubility (or insolubility if taste is an issue)

Two common types of buffer solutions are:

(1) A weak acid together with a salt of the same acid with a strong base. These are called Acid buffers

e.g., CH3COOH + CH3COONa.

(2) A weak base and its salt with a strong acid. These are called Basic buffers. e.g.

NH4OH + NH4Cl.

The principle buffer systems employed for parenteral preparation are acetate, citrate and phosphate.

Name of buffer System Concentration

Acetate CH3COOH + CH3COONa 1-2%

Citrate Citric acid + Na-citrate 1-3%

Phosphate H3PO4 + H salt 0.8-2%

Carbonate H2CO3 + NaHCO3 1-2%

Mechanism of Action

The way buffering agents work is seen in how buffer solutions work. Using Le Chatelier's principle we get an equilibrium expression between the acids and conjugate base. As a result we see that there is little change in the concentrations of the acid and base so therefore the solution is buffered. A buffering agent sets up this concentration ratio by providing the corresponding conjugate acid or base to stabilize the pH of that which it is added to. The resulting pH of this combination can be found by using the Henderson-Hasselbalch equation, which is

Where HA is the weak acid and A is the anion of the base.

The importance‟s of buffer system in pharmaceutical formulation are the following.

Buffered aspirin has a buffering agent, such as MgO, that will maintain the pH of the aspirin as it passes through the stomach of the patient. Another use of a buffering agent is in antacid tablets, whose primary purpose is to lower the acidity of the stomach. Parenteral solutions for injection into the blood are usually not buffered, or they are buffered to a low capacity so that the buffers of the blood may readily bring them within the physiologic pH range. If the drugs are to be injected only in small quantities and at a slow rate, their solutions can be buffered weakly to maintain approximate neutrality. Following oral administration, aspirin is absorbed more rapidly in systemic buffered at low buffer capacity then in systems containing no buffer or in highly buffered preparations. Thus the buffer capacity of the buffer should be optimized to produce rapid absorption and minimal GI irritation of orally administrated aspirin. In addition to the adjustment of tonicity and pH for ophthalmic preparations, similar requirements are demanded for nasal delivery of drugs. Insulin, for example, is more effective by nasal administration than by the other non-parenteral routs. The examples of some buffering excipients that are used in pharmaceutical formulation technology are given below.

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Citric acid: By the concentration of 0.3-.02% improve flavor liquid formulations. 0.3-.02% acts as a suspending and buffering agents and 0.3-.02% also as an antioxidant. Sodium Bicarbonate: A concentration of 1.4% Sodium Bicarbonate is used in the preparation of isotonic injection or infusion solution in pharmaceutical field. Also about 25-50% of Sodium Bicarbonate acts as a source of CO2 in effervescent tablet and granules. Including in some injection (e.g. nicotinic acid) of about 40% of Sodium Bicarbonate to form more soluble sodium salts. Sodium Citrate, Dihydrate and Anhydrous: A concentration of about 0.3 –2.0 % of Sodium Citrate used as a buffering agent in various pharmaceutical formulation like syrup, tablet etc. Also a concentration of 0.3 –2.0 % of Sodium Citrate may acts as sequestering agents.

Chelating agents Chelating agents are molecules that are capable of forming complexes with the drug involving more

than one bond it‟s a complex compound contains one or more ring in its structure .

Complexing agents also called “sequestrants” which form chemical complexes with metallic ions.

Sequestrants are used to stabilize fats and oils which undergo rancidity and reversion in the presence of

the metals copper and iron. By chelating (sequestering) metals, oxidation is slow or entirely prevented.

Calcium-Dinatrium-EDTA E385 is the most used one.

e.g., ethylene diamine is bidentate and ethylene diamine tetraacetic acid is hexadentate.

Uses of chelating agent • EDTA: ethylene diamine tetraacetate is used for the estimation of metals ions.

• EDTAH4: ethylene diamin tetraacetic acid is used for softening water.

• Calcium Disodium Edetate: it is used in the treatment of heavy metal poisoning mostly caused by

lead.

• Disodium Edetate: it is used in hypercalcemic states. It is also useful in the treatment of cardiac

arrhythmias.

Humectants Humectant is a group of hygroscopic substances used to keep things moist. It is the opposite of a

desiccant. They are used to prevent drying of preparations, particularly ointments and creams.

Glycerin, Propylene glycol, Sorbitol

Function Their function is to retard evaporation of aqueous vehicle of dosage form-

• To prevent drying of the product after application to the skin

• To prevent drying of product from the container after first opening

• To prevent cap-locking caused by condensation onto neck of container closure of a container after

first opening

N.B: Cap-locking involves liquid products that recrystallized at the bottle-cap interface and makes

opening the bottle difficult after prolonged periods of non-use. These materials are hygroscopic and

should be stored in well closed containers prior to use.

Typical features of humectant An ideal humectant should have the following criteria-

1. It must absorb moisture from atmosphere and retain the same under the normal conditions of

atmospheric humidity.

2. It should be colourless or not of too intense colour.

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3. It should have good odour and taste.

4. It should be nontoxic and non-irritant.

5. It should be noncorrosive to packaging materials

6. It should not solidify under normal conditions.

7. It should not be too costly.

Classification There are three types of humectants such as inorganic humectants, metal organic humectants and

organic humectants.

1. Inorganic humectants: These are limited used in cosmetics. Calcium chloride is an example. It has

compatibility problems and corrosive in nature. Hence it is not frequently used in cosmetics.

2. Metal organic humectants: These are limited used in cosmetics because of compatibility problems,

corrosive nature and pronounced taste. The example of this class is sodium lactate.

3. Organic humectants: These are widely used in cosmetics. They include polyhydric alcohols, their

esters and ethers. The most commonly used organic humectants are glycerol, ethylene glycol,

polyethylene glycol (PEG), diethylene glycol, tri ethylene glycol, propylene glycol, dipropylene glycol,

glycerin, sorbitol, mannitol, glucose.

Mode of action

• A humectant attracts and retains the moisture in the nearby air via absorption, drawing the water

vapour into and/or beneath the organism/object's surface.

• By contrast, desiccants also attract ambient moisture, but adsorbs -- not absorbs -- it, by condensing

the water vapour onto the surface, as a layer of film.

• Humectants absorb water vapours from atmosphere till a certain degree of dilution is attained.

Aqueous solutions of humectants can reduce the rate of loss of moisture.

Wetting and/or solubilizing agent Reduces the surface tension of water, allowing it to spread more easily, and/or improves the solubility

of poorly water soluble drugs. They increase the spreading and penetrating properties of a liquid by

lowering its surface tension.

The surface tension of a liquid is the tendency of the molecules to bond together, and is determined by

the strength of the bonds or attraction between the liquid molecules. A wetting agent stretches theses

bonds and decreases the tendency of molecules to bond together, which allows the liquid to spread

more easily across any solid surface.

Examples

e.g.

• Oral: polysorbates (Tweens), sorbitan esters (Spans)

• Parenteral: polysorbates, poloxamers, lecithin

• External: sodium lauryl sulphate

But these can cause excessive foaming and can lead to deflocculation and undesirable physical instability

(sedimentation) if levels too high.

Hydrophilic colloids that coat hydrophobic particles, e.g. bentonite, tragacanth, alginates, cellulose

derivatives. Also used as suspending agents, these can encourage deflocculation if levels are too low.

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[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Solvents/Co-Solvents Solvent: A solvent is a substance that can dissolve a solute (a chemically different liquid, solid or gas)

resulting in solution. A solvent is usually a liquid but it can also be solid or a gas. A solvent never

changes its state forming a solution. Water and hydroalcoholic alcohol, water and glycerin may be used

as co-solvents when needed. Sterile solvents are used in preparations such as injections.

Ideal characteristics of solvent 1. It should either dissolve or disperse the polymer system.

2. It should easily disperse other coating solution component into the solvent system.

3. Small concentration of polymer (2-10%) should not result in an extremely viscous solution system

(>300cps) creating processing problem.

4. It should be colorless, tasteless, odorless, in-expensive, non-toxic, inert and non-flammable.

5. It should have rapid drying rate.

6. It should have no environmental impact.

Classification On the basis of the forces of interaction occurring in solvents, one may broadly classify solvents as one

of three types:

1. Polar solvents: Those made up of strong dipolar molecules having hydrogen bonding are known as

polar solvent. e.g., water or hydrogen peroxide.

2. Semi-polar solvents: Those also made up of strong dipolar molecules but that do not form hydrogen

bonds are known as semi-polar solvent. e.g., acetone or pentyl alcohol.

3. Non-polar solvents: Those made up of molecules having a small or no dipolar characters are known

as non-polar solvent. e.g., benzene, vegetable oil, or mineral oil.

Normally solvation of a solvent depends upon its classification. Generally polar solvent dissolves polar

compound best and non-polar solvent dissolves non polar compound best.

Examples

• The first choice for a solvent is water in which a drug is freely soluble.

• Water –miscible solvent such as Chlordiazepoxide hydrochloride can be used to improve solubility and

stability.

• Oils are used as emulsion; intramuscular injections and liquid fill oral preparation.

• Aqueous methanol is widely used in HPLC and is the standard solvent in sample extraction.

• Other acceptable non-aqueous solvents are glycerol, propylene glycol, ethanol and are used generally

for a lipophilic drug.

Water is the solvent most widely used as a vehicle due to

constant), but

Likely to cause instability of hydrolytically unstable drugs

Good vehicle for microbial growth

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Co-solvent Co-solvents are defined as water-miscible organic solvents that are used in liquid drug formulations to

increase the solubility of poorly water soluble substances or to enhance the chemical stability of a drug.

Properties of co-solvent

• Co-solvent increases the solubility of a drug.

• An ideal co-solvent should possess values of dielectric constant between 25 and 80.

• The most widely used system that will cover this range is a water/ethanol blend.

• It should not cause toxicity or irritancy when administrated for oral or parental use

• Other co-solvents are sorbitol, glycerol, propylene glycol and syrup.

Application of co-solvent

Water-miscible co-solvents are used to:

Enhance solubility, taste, anti-microbial effectiveness or stability

Reduce dose volume (e.g. oral, injections) Or, conversely, optimise insolubility (if taste of API is an

issue)

Examples: propylene glycol, glycerol, ethanol, low molecular weight PEGs

Water-immiscible co-solvents, e.g. Emulsions / microemulsions using fractionated coconut oils

Complexing agents Complexing agents are widely used in various industrial processes and household products throughout

the world. Amongst the well-known complexing agents, not only EDTA but also DTPA (Pentetic acid or

diethylenetriaminepentaacetic acid (DTPA) is an aminopolycarboxylic acid consisting of a

diethylenetriamine backbone with five carboxymethyl groups. The molecule can be viewed as an

expanded version of EDTA and is used similarly. It is a white, water-soluble solid.) and NTA

(Nitrilotriacetic acid (NTA) is the aminopolycarboxylic acid with the formula N(CH2CO2H)3. It is a

colourless solid that is used as a chelating agent, which forms coordination compounds with metal ions

(chelates) such as Ca2+, Cu2+, and Fe3+ ) are widely used.

These substances that forms stable water-soluble complexes (chelates) with metals and are used in some

liquid pharmaceuticals as stabilizers to complex heavy metals that might promote instability. In such use,

they are also called sequestering agents.

Stiffening agents Stiffening agent excipients are used primarily in topical preparations for increasing the preparation‟s viscosity or thickness or hardness. Often stiffening agents find application as sustained-release carriers

and to minimize sweating and bleeding of oil-wax blends.

Examples: cetyl alcohol, cetyl esters wax, microcrystalline wax, paraffin, stearyl alcohol, white wax,

yellow wax

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Essentials for real life exam and via board

Antiadherents Antiadherents reduce the adhesion between the powder (granules) and the punch faces and thus prevent sticking to tablet punches by offering a non-stick surface. They are also used to help protect tablets from sticking. The most commonly used is magnesium stearate. Other

includes Talc, Starch, Cellulose

Antiadherent: The function of an antiadherent is to reduce adhesion between the powder and the punch faces and thus

prevent particles sticking to the punches. Many powders are prone to adhere to the punches, a phenomenon (known in the

industry as sticking or picking) which is affected by the moisture content of the powder. Such adherence is especially prone

to happen if the tablet punches are engraved or embossed. Adherence can lead to a build-up of a thin layer of powder on

the punches, which in turn will lead to an uneven and matt tablet surface with unclear engravings. Many lubricants, such as

magnesium stearate, have also antiadherent properties. However, other substances with limited ability to reduce friction can

also act as antiadherents, such as talc and starch. Glidants Functions of glidants: Glidants are used to promote powder flow by reducing interparticle friction and cohesion. These are used in combination with lubricants as they have no ability to reduce die wall friction. Examples of Glidants: Silica, Magnesium stearate, Talc, Fumed silica, Colloidal silicon dioxide, talc, syloid, aerosil and magnesium carbonate. The role of the glidant is to improve the flowability of the powder. This is especially important during tablet production at

high production speeds and during direct compaction. However, because the requirement for adequate flow is high, a glidant

is often also added to a granulation before tabletting.

Lubricants Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall. Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsules. Others include: Magnesium stearate, Stearic acid, Polyethylene glycol, Sodium lauryl sulphate, Sodium stearyl fumarate, Liquid

paraffin Lubricants are agents added in small quantities to tablet and capsule formulations to improve certain processing characteristics.

Lubrication is achieved by mainly two mechanisms: Fluid lubrication and boundary lubrication.

Fig. 27.8 Schematic illustration of lubrication mechanisms by fluid and boundary lubrication.

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There are three roles identified with lubricants as follows:

True lubricant role: To decrease friction at the interface between a tablet’s surface and the die wall during ejection and reduce wear on punches & dies.

Anti-adherent role: Prevent sticking to punch faces or in the case of encapsulation, lubricants. Prevent sticking to machine dosators, tamping pins, etc.

Glidant role: Enhance product flow by reducing interparticulate friction.

There are two major types of lubricants:

Hydrophilic: Generally poor lubricants, no glidant or anti-adherent properties.

Hydrophobic: Most widely used lubricants in use today are of the hydrophobic category. Hydrophobic lubricants are generally good lubricants and are usually effective at relatively low concentrations. Many also have both anti- adherent and glidant properties. For these reasons, hydrophobic lubricants are used much more frequently than hydrophilic compounds. Examples include magnesium stearate.

Table: Different between glidant and lubricant

Glidant Lubricant

1. A substance that is added to a powder to improve its flowability.

1. A substance used to reduce friction between objects or surfaces.

2. The glidant is often added to a granulation before tableting.

2. Lubricant gives action after tableting.

A Glidant's effect is due correcting surface irregularity, reducing interparticular friction & decreasing surface charge.

lubrication is achieved by Thick-Film lubrication (Fluid-Film or hydrodynamic lubrication) , Thin Film lubrication (Boundary lubrication) and Extreme Pressure lubrication

4. They reduce the interparticulate friction. 4. Reduce friction between solid and die cavity. 5. Usually glidant are solid. 5. Lubricant may be liquid.

6. e.g. Silica, Magnesium carbonate, talc, syloid, aerosil etc.

6. e.g. Stearic acid, Magnesium stearate, Calcium stearate, polyethylene glycol etc.

Binders

Binders hold the ingredients in a tablet together. Binders ensure that tablets and granules can be formed by increasing cohesive state of the drug powder, with required mechanical strength. In other word according to WHO binders act as an adhesive to ‘bind together’ powders, granules and tablets to result in the necessary mechanical strength. Binders can be added to a powder in different ways:

As a dry powder which is mixed with the other ingredients before wet agglomeration. During the agglomeration procedure the binder might thus dissolve partly or completely in the agglomeration liquid;

As a solution which is used as agglomeration liquid during wet agglomeration. The binder is here often referred to as a solution binder.

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[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

As a dry powder which is mixed with the other ingredients before compaction

(slugging or tabletting). The binder is here often referred to as a dry binder.

As a dry powder with other excipients in dry granulation (roller compaction, slugging) or as an extra-granular excipient in a wet granulation tablet formulation.

As a dry powder with other intra-granular excipients in wet granulation. When the granulating fluid is added, the binder may dissolve partially or completely to then exhibit adhesive binding properties in helping granules to form.

Most commonly in wet granulation, the binder is added already dissolved in the granulating fluid to enable a more effective and controllable granule formation.

Important examples of dry binders.

Saccharides and their derivatives: o Disaccharides: sucrose, lactose; o Polysaccharides and their derivatives: starches, cellulose or modified cellulose

such as microcrystalline cellulose and cellulose ethers such as hydroxypropyl cellulose (HPC);

o Sugar alcohols such as xylitol, sorbitol or maltitol; Protein: gelatin; Synthetic polymers: polyvinylpyrrolidone (PVP), polyethylene glycol (PEG).

Typical features of binders: A binder should

Be compatible with other products of formulation and

Add sufficient cohesion to the powders. Classification and examples: Binders are classified according to their application,

Dry binders are added to the powder blend, either after a wet granulation step, or as part of a direct powder compression (DC) formula. e.g., Pregelatinised starch, cross-linked PVP, cellulose, methyl cellulose, and polyethylene glycol.

Solution binders are dissolved in a solvent (for example water or alcohol can be used in

wet granulation processes). e.g., PVP, HPMC, gelatin, cellulose, cellulose derivatives, starch, sucrose and polyethylene glycol.

Soluble in water/ethanol mix: PVP

Acacia, Tragacanth, Gelatin, Sucrose, Starch paste are soluble in water and are not used in

water sensitive drugs, while Na-alginate, Methyl cellulose dissolved in alcohol and PVP, Methyl

cellulose drugs, while Na-alginate, Hydroxy Propyl cellulose dissolved both water and alcohol.

In case of water sensitive drugs first bender need to dissolve on alcohol and then other

excipients and active ingredients are mixed with it.

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[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Other example of binders include Alginic Acid, Sodium alginate, Carboxymethyl cellulose

sodium (CMC), Microcrystalline cellulose (MCC), Powdered cellulose, Confectioner’s sugar, Dextrin, Dextrose, Ethylcellulose, Guar gum, Hydroxypropyl cellulose (HPC), Hypromellose

(HPMC), Lactose, Maltodextrin, Methylcellulose, Povidone, Zein.

Table: Some binders their concentration and required solvent are given below.

Binders Used concentration Required solvent 1. Acacia 2-5% H2O 2. Tragacanth 1-3% H2O 3. Sucrose 2-20% H2O 4. Gelatin 1-4% H2O 5. Starch past 1-4% H2O 6. Na-alginate 3-5% Alcohol 7. Methyl cellulose 1-4% Alcohol 8. Pyrrolidone 2-5% H2O and Alcohol 9. Ethyl celluese 0.2-0.5% H2O and Alcohol

Diluents/ Fillers

When the quantity of a drug for an individual dose is very small then it is practically impossible to compress then the inert substances which are added to increase the bulk for easy compression a known as filler or the diluent. Diluent’s are filler used to make required bulk of tablet when the dosage itself is inadequate to produce this bulk. Secondary reason is to provide better tablet properties such improved cohesion, to permit use of direct compression manufacturing, or to promote flow. Fillers typically also fill out the size of a tablet or capsule, making it practical to produce and convenient for the consumer to use. e.g., Minimum tablet weight is typically ~50mg. Actual API doses can be as low as ~20μg, e.g. for oral steroids. In order to form tablets of a size suitable for handling, a lower limit in terms of powder volume and weight is required. Tablets weigh normally at least 50 mg. Therefore, a low dose of drug per tablet requires the incorporation of a substance into the formulation to increase the bulk volume of the powder and hence the size of the tablet. This excipient, known as the filler or the diluent, is not necessary if the dose of the drug per tablet is high.

Function of fillers

Bulking agent: Fillers add volume and/or mass to a drug substance, thereby facilitating precise metering and handling thereof in the preparation of dosage forms . Used in tablets and capsules.

Compression aid: Deforms and/or fragments readily to facilitate robust bonding in tablet

compacts, e.g. microcrystalline cellulose.

Good bulk powder flow diluents have a strong influence: Good flow of bulk powders is very important in designing a robust commercial tablet product.

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[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

Typical features of fillers: An ideal diluent should have the following criteria- 1. They should typically be inert and non-toxic.

2. They should have an acceptable taste.

3. They must be compatible with the other components of the formulation.

4. They must be physically and chemically stable.

5. They must be non-hygroscopic.

6. They must be free from any unacceptable microbiologic load.

7. They must be commercially available is all acceptable grade.

8. They do not alter bioavailability of the drug.

9. They must be colour compatible. 10. They should be biocompatible 11. They should possess good biopharmaceutical properties (e.g. water soluble or hydrophilic) 12. They should possess good technical properties (such as compactability and dilution capacity) 13. They should be cheap. Examples: Plant cellulose and dibasic calcium phosphate are used popularly as fillers. A range of vegetable fats and oils can be used in soft gelatin capsules. Other examples of fillers include: lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, calcium sulfate, magnesium stearate, Microcrystalline cellulose (MCC), Powdered cellulose, Dextrates, Dextrin, Dextrose, Kaolin, Maltodextrin, Starch, Sucrose Lactose, Sucrose, Glucose, Mannitol, Sorbitol, Calcium phosphate, Calcium carbonate, Cellulose

Favoured combinations: Lactose is an excellent choice of filler in many respects but can exhibit poor flow characteristics, so is often combined with free-flowing microcrystalline cellulose in wet granulation formulations.

Disintegrants Disintegrants are substances or mixture of substances added to the drug formulations, which facilitate dispersion or breakup (disintegration) of tablets and contents of capsules into smaller particles for quick dissolution when it comes in contact with water in the GIT. They are mainly two types- a. Substances which hydrate and swell up in contact with water.

b. Substances which react with effervescent when they come in contact with moisture for example combination of Na-CO3, citric acid and tartaric acid. Ideal properties of disintigrants Good hydration capacity, poor solubility, poor gel formation capacity. Mode of action: The disintegration process for a tablet occurs in two steps. First, the liquid wets the solid and secondly penetrates the pores of the tablet. Thereafter, the tablet breaks into smaller fragments. Disintegrants that facilitate water uptake: These disintegrants act by facilitating the transport of liquids into the pores of the tablet, with the consequence that the tablet may break into fragments. One obvious type of substance that can promote liquid penetration is surface active agents. Disintegrants that will rupture the tablet: Rupturing of tablets can be caused by swelling of the disintegrant particles during sorption of water.

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• In many cases water uptake alone will cause disintegration, by rupturing the intra-particle cohesive forces that hold the tablet together and resulting in subsequent disintegration.

• If swelling occurs simultaneously with water uptake, the channels for penetration are widened by physical rupture and the penetration rate of water into the dosage form increased.

• Evaluation of CO2 on effervescent tablet is one of the ways of disintegration.

And a third group of disintegrant functions by producing gas, normally carbon dioxide, in contact with water. Such disintegrants are used in effervescent tablets and normally not in tablets that should be swallowed as a solid.

Examples: The most traditionally used disintegrant in conventional tablets is starch, among which potato, maize and corn starches are the most common types used. PVP, CMC, Sodium starch glycolate, Alginic Acid, Sodium alginate, Microcrystalline cellulose (MCC), Croscarmellose sodium, Crospovidone, Guar gum, Polyacrilin Potassium, Sodium Starch Glycolate, Veegum HV, bentonite 10% and cellulose derivatives Ac-Di-Sol(Na-CMC), Alginate. Q. Why are disintegrates added in two fractions for the formulation of tablet dosage form? During manufacturing the tablets disintegrating agents are added in two steps- a. Major part is incorporated to the powder before granulation.

b. Other part is mixed with the dried granulation along with lubricants before compression. Disintegrates are added in a manner to serve two purposes- a. The disintegrates added after granulation breaks the tablet apart into granules

b. The portion added before granulation convert granules into fine particles thus facilitating tablet dissolution. The disintegrating time depend on- 1. Quality of diluent, binder, lubricant

2. Hardness of tablet

3. Size of granules

4. And finally on coating. Super disintegrates: These disintegrates which swells up to 10 to fold within 30 seconds when they water. Significant improvement in disintegrant performance was achieved with the introduction of the first super disintegrant. For example- Cross carmellose-cross linked cellulose crosslinked sodium carboxymethyl cellulose (croscarmellose

sodium).

crosslinked polyvinylpyrrolidone (crospovidone Sodium starch glycolate-cross linked starch.

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List of Superdisintegrants

Superdisintegrants Example of Mechanism of action Special comment

Crosscarmellose(r)

Ac-Di-Sol(r)

Nymce ZSX(r)

Primellose(r)

Solutab(r)

Vivasol(r)

Crosslinked

cellulose

-Swells 4-8 folds in <

10 seconds.

-Swelling and wicking

both.

-Swells in two

dimensions.

-Direct compression

or granulation

-Starch free

Crosspovidone

Crosspovidon M(r)

Kollidon(r)

Polyplasdone(r)

Crosslinked PVP

-Swells very little and

returns to original

size after

compression but act

by capillary action

-Water insoluble and

spongy in nature so

get porous tablet

Sodium starch glycolate

Explotab(r)

Primogel(r)

Crosslinked starch -Swells 7-12 folds in

<30 seconds

-Swells in three

dimensions and high

level serve as sustain

release matrix

Alginic acid NF

Satialgine(r)

Crosslinked alginic

acid

-Rapid swelling in

aqueous medium or

wicking action

-Promote

disintegration in

both dry or wet

granulation

Soy polysaccharides

Emcosoy(r)

Natural super

disintegrant

-Does not contain

any starch or sugar.

Used in nutritional

products.

Calcium silicate

-Wicking action

-Highly porous,

-light weight

-optimum

concentration is

between 20-40%

Granulating Agents Granulating agents are the substances which are added to powders during granulating process to convert fine powders into granules. Insufficient quantity of granulating agent may lead to poor adhesion, soft tablets and capping, where as excessive quantity may lead to hard tablets into grater disintegration time.

Example: Commonly used granulating agents are water, mucillages of acacia, tragacanth, Copolyvidone, sucrose and starch. Liquid glucose syrup and alcohol in various dilutions. Alcohols are used for water sensitive drug.

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[email protected]; Lecturer; Department of Pharmacy; Primeasia University.

EXAMPLES OF PHARMACEUTICAL INGREDIENTS

Ingredient type Definition Examples

Acidifying agent Used in liquid preparations to provide acidic medium for

product stability

Citric acid

Acetic acid

Fumaric acid

Hydrochloric acid

Nitric acid

Alkalinizing agent Used in liquid preparations to provide alkaline medium for

product stability

Ammonia solution

Ammonium carbonate

Diethanolamine

Monoethanolamine

Potassium hydroxide

Sodium bicarbonate

Sodium borate

Sodium carbonate

Sodium hydroxide

Trolamine

Adsorbent An agent capable of holding other molecules onto its surface by

physical or chemical (chemisorption) means

Powdered cellulose

Activated charcoal

Aerosol propellant Agent responsible for developing the pressure within an aerosol

container and expelling the product when the valve is opened

Carbon dioxide

Dichlorodifl uoromethane

Dichlorotetrafl uoroethane

Trichloromonofl

uoromethane

Air displacement Agent employed to displace air in a hermetically sealed

container to enhance product stability

Nitrogen

Carbon dioxide

Antifungal preservative Used in liquid and semisolid preparations to prevent growth of

fungi. Effectiveness of parabens is usually enhanced by use in

combination

Butylparaben

Ethylparaben

Methylparaben

Benzoic acid

Propylparaben

Sodium benzoate

Sodium propionate

Antimicrobial preservative

Used in liquid and semisolid preparations to prevent

growth of microorganisms

Benzalkonium chloride

Antioxidant Used to prevent deterioration of preparations by

oxidation

Ascorbic acid

Ascorbyl palmitate

Butylated hydroxyanisole

Butylated hydroxytoluene

Hypophosphorous acid

Monothioglycerol

Propyl gallate

Sodium ascorbate

Sodium bisulfi te

Sodium formaldehyde

Sulfoxylate

Sodium metabisulfi te

Buffering agent Used to resist change in pH upon dilution or addition of acid or

alkali

Potassium metaphosphate

Potassium phosphate,

monobasic

Sodium acetate

Sodium citrate, anhydrous

and dihydrate

Chelating agent Substance that forms stable water-soluble complexes (chelates)

with metals; used in some liquid pharmaceuticals as stabilizers

to complex heavy metals that might promote instability. In such

Edetic acid

Edetate disodium

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use, they are also called sequestering agents

Colorant Used to impart colour to liquid and solid

(e.g., tablets and capsules) preparations

FD&C Red No. 3

FD&C Red No. 20

FD&C Yellow No. 6

FD&C Blue No. 2

D&C Green No. 5

D&C Orange No. 5

D&C Red No. 8

Caramel, Ferric oxide, red

Clarifying agent Used as a filtering aid for its adsorbent qualities Bentonite

Emulsifying agent Used to promote and maintain dispersion of finely subdivided

particles of liquid in a vehicle in which it is immiscible. End

product may be a liquid emulsion or semisolid emulsion (e.g., a

cream)

Acacia

Cetomacrogol

Cetyl alcohol

Glyceryl monostearate

Sorbitan monooleate

Polyoxyethylene 50 stearate

Encapsulating agent Used to form thin shells to enclose a drug for ease of

administration

Gelatin

Flavorant Used to impart a pleasant flavour and often odour to a

preparation. In addition to the natural flavorants listed, many

synthetic ones are used

Anise oil

Cinnamon oil

Cocoa

Menthol

Orange oil

Peppermint oil

Vanillin

Humectant Used to prevent drying of preparations, particularly ointments

and creams

Glycerin

Propylene glycol

Sorbitol

Levigating agent Liquid used as an intervening agent to reduce the particle size

of a powder by grinding, usually in a mortar

Mineral oil

Glycerin

Propylene glycol

Ointment base Semisolid vehicle for medicated ointments Lanolin

Hydrophilic ointment

Polyethylene glycol

ointment

Petrolatum

Hydrophilic petrolatum

White ointment

Yellow ointment

Rose water ointment

Plasticizer Component of fi lm-coating solutions to make fi lm more

pliable, enhance spread of coat over tablets, beads, and

granules

Diethyl phthalate

Glycerin

Solvent Used to dissolve another substance in preparation of a solution;

may be aqueous or not (e.g., oleaginous). Co-solvents, such as

water and alcohol (hydroalcoholic) and water and glycerin, may

be used when needed. Sterile solvents are used in certain

preparations (e.g., injections)

Alcohol

Corn oil

Cottonseed oil

Glycerin

Isopropyl alcohol

Mineral oil

Oleic acid

Peanut oil

Purified water

Water for injection

Sterile water for injection

Sterile water for irrigation

Stiffening agent Used to increase thickness or hardness of a preparation, usually

an ointment

Cetyl alcohol

Cetyl esters wax

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Microcrystalline wax

Paraffi n

Stearyl alcohol

White wax

Yellow wax

Suppository base Vehicle for suppositories Cocoa butter

Polyethylene glycols

(mixtures)

PEG 3350

Surfactant (surface active agent)

Substances that absorb to surfaces or interfaces to

reduce surface or interfacial tension. May be used

as wetting agents, detergents, or emulsifying agents

Benzalkonium chloride

Nonoxynol 10

Octoxynol 9

Polysorbate 80

Sodium lauryl sulfate

Sorbitan monopalmitate

Suspending agent Viscosity-increasing agent used to reduce sedimentation rate of

particles in a vehicle in which they are not soluble; suspension

may be formulated for oral, parenteral, ophthalmic, topical, or

other route

Bentonite

Carbomer (e.g., Carbopol)

Carboxymethylcellulose

sodium

Hydroxyethyl cellulose

Hydroxypropyl cellulose

Hydroxypropyl

methylcellulose

Kaolin

Methylcellulose

Tragacanth

Veegum

Sweetening agent Used to impart sweetness to a preparation Aspartame

Dextrose

Glycerin

Mannitol

Saccharin sodium

Sorbitol

Sucrose

Tablet antiadherents Prevent tablet ingredients from sticking to punches

and dies during production

Magnesium stearate

Tablet binders Substances used to cause adhesion of powder

particles in tablet granulations

Acacia

Alginic acid

Carboxymethylcellulose

sodium

Compressible sugar (e.g.,

Nu-Tab)

Ethylcellulose

Gelatin

Liquid glucose

Methylcellulose

Povidone

Pregelatinized starch

Tablet and capsule diluent

Inert filler to create desired bulk, flow properties,

and compression characteristics of tablets and

capsules

Dibasic calcium phosphate

Kaolin

Lactose

Mannitol

Microcrystalline cellulose

Powdered cellulose

Precipitated calcium

carbonate

Sorbitol

Starch

Tablet coating agent Used to coat a tablet to protect against decomposition by

atmospheric oxygen or humidity, to provide a desired release

pattern, to mask taste or odour, or for aesthetic purposes.

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Coating may be sugar, fi lm, or thick covering around a tablet.

Sugar-coated tablets generally start to break up in the stomach.

Film forms a thin cover around a formed tablet or bead. Unless

it is enteric, film dissolves in the stomach. Enteric coating

passes through the stomach to break up in the intestines. Some

water-insoluble coatings (e.g., ethylcellulose) are used to slow

the release of drug in the gastrointestinal tract

Sugar coating Liquid glucose

Sucrose

Film coating Hydroxyethyl cellulose

Hydroxypropyl cellulose

Hydroxypropyl

methylcellulose

Methylcellulose

(e.g., Methocel)

Ethylcellulose (e.g., Ethocel)

Enteric coating Cellulose acetate phthalate

Shellac (35% in alcohol,

pharmaceutical glaze)

Tablet direct compression excipient

Used in direct compression tablet formulations Dibasic calcium phosphate

(e.g., Ditab)

Tablet disintegrant Used in solid forms to promote disruption of the mass into

smaller particles more readily dispersed or dissolved

Alginic acid

Polacrilin potassium

(e.g., Amberlite)

Sodium alginate

Sodium starch glycolate

Starch

Tablet glidant Used in tablet and capsule formulations to improve flow

properties of the powder mixture

Colloidal silica

Cornstarch

Talc

Tablet lubricant Used in tablet formulations to reduce friction during tablet

compression

Calcium stearate

Magnesium stearate

Mineral oil

Stearic acid

Zinc stearate

Tablet or capsule opaquant

Used to render a coating opaque. May be used alone or with a

colorant

Titanium dioxide

Tablet polishing agent Used to impart an attractive sheen to coated tablets Carnauba wax

White wax

Tonicity agent Used to render solution similar in osmotic-dextrose

characteristics to physiologic fluids, e.g., in ophthalmic,

parenteral, and irrigation fluids

Sodium chloride

Vehicle Carrying agent used in formulating a variety of liquids for oral

and parenteral administration. Generally, oral liquids are

aqueous (e.g., syrups) orhydroalcoholic (e.g., elixirs). Solutions

for intravenous use are aqueous, whereas intramuscular

injections may be aqueous or oleaginous

Flavored, sweetened Acacia syrup

Aromatic syrup

Aromatic elixir

Cherry syrup

Cocoa syrup

Orange syrup

Syrup

Oleaginous Corn oil

Mineral oil

Peanut oil

Sesame oil

Sterile Bacteriostatic sodium

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chloride injection

Viscosity-increasing agent Used to render preparations more resistant to

flow. Used in suspensions to deter sedimentation,

in ophthalmic solutions to enhance contact

time (e.g., methylcellulose), to thicken topical

creams, etc.

Alginic acid

Bentonite

Carbomer

Carboxymethylcellulose

Sodium

Methylcellulose

Povidone

Sodium alginate

Tragacanth

REFERENCES

A.K. Gupta, S.S Bajaj:Introduction to pharmaceutics-II; CBS Puplishers and distributors ,New Delhi India, 2009

Chapter Six .

Loyd V. Allen, Jr., PhD; Nicholas G. Popovich, PhD; Howard C. Ansel, PhD : Ansel‟s Pharmaceutical Dosage

Forms and Drug Delivery Systems; Lippincott Williams & Wilkins, Philadelphia 2011 Chapter four 128-132

M.E. Aulton: Pharmaceutics -The science of Dosage form Design, Churchill Living Stone, Second Edition

Remington :Essentials of Pharmaceutics; First edition; Pharmaceutical Press; 1 Lambeth High Street, London

SE1 7JN, UK; 2013, Chapter 36

Raymond C Rowe,Paul J Sheskey,Marian E Quinn : Handbook of Pharmaceutical Excipients, Sixth edition;

Pharmaceutical Press; 1 Lambeth High Street, London SE1 7JN, UK; 2009