pharmaceutical excipients

Shamiul Bashar 1st Batch

B. Pharm, VU

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Pharmaceutical Excipients

Q. Define excipients. Why excipients are used in pharmaceutical preparation?

Excipient: Drug products contain both drug substance (commonly referred to as active

pharmaceutical ingredient or API) and excipients. An excipient is a pharmacologically inactive/ inert

substance formulated alongside the active pharmaceutical ingredient of a medication.

Excipients play a wide variety of functional roles in pharmaceutical dosage form, including-

1. Provide bulk to the formulation.

2. Aid in handling of “API” during manufacturing.

3. Ease of administration to the target patient population(s) by the intended route.

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

of the formulation).

5. Facilitate drug absorption or solubility and other pharmacokinetic considerations.

6. Modulating solubility & bioavailability of APIs.

7. Consistency and control of drug bioavailability.

8. To enable bioavailability.

9. Improved API stability in dosage forms including protection from degradation/ denaturation.

10. To ensure a robust and reproducible physical product.

11. Helping active ingredients maintains preferred polymorphic forms or conformations,

12. Maintaining the pH and /or osmolarity of the liquid formulations,

13. Preventing aggregation or dissociation (e.g. of protein and polysaccharide actives).

14. Modulating immunogenic responses of active ingredients (e.g. adjuvants), and more.

N.B: Excipients, in certain cases, interacts with the active ingredient in the final formulated

dosage form or may provide a matrix that affects the critical quality attributes of the active ingredients

like stability and bioavailability.

Q. Classify excipients.

There are various types of excipients available in pharmaceutical formulation. They are,

1. Diluents. (Fillers/ bulking agents)

2. Binders.

3. Disintegrating agents.

4. Granulating agents.

5. Lubricants.

6. Glidants.

7. Preservatives.

8. Antioxidant.

9. Flavouring agents.

10. Sweeting agents.

11. Colouring agents.

12. Ointment base.

13. Solvent & Co-solvent.

14. Buffering Agents.

15. Chelating Agents.

16. Viscosity imparting Agents.

17. Surface Active Agents/ Surfactants.

18. Coating agents.

19. Sorbents.

20. Humectants.

Q. Write down the fundamental characteristic of pharmaceutical excipients.

Properties of an ideal excipient:

1. It should be feasible.

2. It should be nontoxic, nonirritant.

3. It should be nonvolatile.

4. It should be stable itself and not affected by temperature, light and hydrolysis.

5. It should be readily available and cheap.

6. It should be colourless, odourless and tasteless.

7. It should be soluble in water as well as oil and fat.

8. It should be compatible with the active ingredient in the preparation.

9. It should have no interaction with the API.

10. It should be pharmacologically inert in the formulation.



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Q. Write down the innovation in pharmaceutical excipients.

Innovation in pharmaceutical excipients: In general, there are three types of new excipients and

the development process of these varies significantly:

Modified Excipients: Well known excipients with established quality standards can be

modified with regard to their impurity profile or their physical properties. The development

for modified excipients time is relatively short with a low R&D investment and a low

associated risk.

Co-Processed Excipients: Two or more excipients are formulated without chemical changes

in order to achieve new performance characteristics which cannot be achieved by simple

physical mixing. The development of a co-processed excipient is more complex.

Novel Excipients: It is used for the first time in a drug product or a new route of

administration. Novel excipient’s development is substantially similar to the non-clinical

development of a new active ingredient: A high R&D investment and a long development

time.

As a consequence, only very few manufacturers are willing to invest in the development of a

novel excipient.

Product development of new excipients has three main goals:

To demonstrate the advantage over existing materials for the target application.

To establish a reliable manufacturing process that leads to the desired product

characteristics.

To demonstrate the appropriate stability of the new grade.

Q. Elucidate the different functional roles of excipients in different formulation.

The excipients, ingredients other than the active pharmaceutical ingredient, in a dosage form have

different functionalities, depending on how they are used in a formulation or the type of formulation

they are incorporated into. For a more in-depth discussion addressing dosage form development and

manufacturing concerns around excipient choice and use.

Certain excipients can have different functional roles in different formulation types, e.g. lactose;

widely used as:

• A diluent, filler or bulking agent in tablets and capsules

• A carrier for dry powder inhalation products (DPIs).

Furthermore, individual excipients can have different grades, types and sources depending on

those different functional roles.

For example, there are various grades of lactose commercially available that have different

physical properties, e.g. flow characteristics & particle size distributions. This permits selection of the

most suitable grade for a particular need.

• Wet Granulation: usually, finer grades of lactose are used so that the binder is more efficient

and this permits better mixing and granule quality.

• Direct Compression: in contrast here, spray dried lactose is used as it has good flow

properties and is more compressible.

• For dry powder inhalers: crash-crystallisation fine-milled lactose with a coarser fraction for

flow and a finer fraction to enhance API aerosolisation and delivery to the lungs.


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Q. Define stability of pharmaceutical preparation and stabilizer. Classify it.

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

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

therapeutic and toxicological specifications.

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

The most important stabilizers are,

1. Antioxidants and

2. Preservatives.

Diluents/ Fillers

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.

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 diluents. 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.

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.

Typical features of fillers: An ideal diluent should have the following criteria-

1. They should typically be inert and non-toxic.

2. They should be preferably tasteless or pleasant tasting.

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 color compatible.

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

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.


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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:

• 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.

• Water is the most common granulating fluid, very occasionally in a co-solvent system with,

e.g. ethanol.

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. 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


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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:

• 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.

Examples: 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 par 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

Cross providone- cross linked providone

Sodium starch glycolate-cross linked starch.

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


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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.

Antiadherents, Lubricants & Glidants

Antiadherents: Antiaderents or anti-sticking agents prevent adhesion of the tablet surface to the

die walls and the punches and as a consequence counter the picking or sticking of tablet.

Examples of Antiadherents: Water insoluble lubricants such as magnesium stearate can be

used as antiadherents , as can talc and starch.

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.

Types:

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

2. 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.

Roles of lubricants:

1. 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.

2. Anti-adherent Role:

• Prevent sticking to punch faces or in the case of encapsulation, lubricants

• Prevent sticking to machine dosators, tamping pins, etc.

3. Glidant Role:

• Enhance product flow by reducing interparticulate friction

Examples of lubricants: Polyethylene glycol, Stearic acid, Magnesium stearate, Calcium stearate,

Glyceryl monostearate, Isopropyl Myristate, Polyvinyl Alcohol, Sodium Stearyl Fumarate, Talc

Glidants: A substance (as colloidal silica) that enhances the flow of a granular mixture by reducing

inter-particle friction and that is used in the pharmaceutical production of tablets and capsule.

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: Fumed silica, Colloidal silicon dioxide, talc, syloid, aerosil and magnesium

carbonate.


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Table: Different between glidant and lubricant

Glidant Lubricant

1. It improves the flow ability of the powder. 1. It ensures tablet formulation and ejection

with low fraction.

2. The glidant is often added to a granulation

before tableting.

2. Lubricant gives action after tableting.

3. They adhere particle surface of the other

ingredients and improve flow.

3. They adhere to the die wall.

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.

Preservatives

Preservatives are substances that commonly added to various foods and pharmaceutical products to

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

Some preservatives, either by concentration or activity, may only maintain the bacteria level in the

product at the time of manufacture and are referred to as bacteriostatic preservatives.

Ideal properties of preservatives: In concept, the preservative system protects the product

against microbial proliferation but does not compromise product performance. In practice, this means

that it must:

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 effective against a wide range of microorganisms such as bacteria, mold and

fungi etc at room temperature.

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

7. It should be nontoxic and non-sensitizing.

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

9. If the system is biphasic, the partition-coefficient should be in favor of the aqueous phase.

10. It should be effective at low concentration.

11. It should be nontoxic, nonirritant.

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

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

14. It should be neutral and should not react chemically with other constituent.

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

16. It should be thermostable

17. It should preserve the preparations and remain stable for the shelf life of the product.

Examples: Methylparaen, Ethyl parabens, Propylparaben, Butylparaben, Benzoic acid and its salts,

Sorbic acid , Potassium Sorbate. Alcohol, Benzalkonium chloride, Boric acid, Butylated

Hydroxyanisole (BHA), Butylated Hydroxytoluene (BHT), Phenol, Phenethyl Alcohol, , Propylene

Glycol.


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

pharmaceutical formulation.

Combine preservatives: The use of two or more preservative collectively known as combine

preservative.

No single preservative possesses all the ideal properties. Sometime a single preservative in 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. Then two

or more preservatives are used to increase their preservatives action. In combine preservatives, have a

broad spectrum of 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.

Q. How you will evaluate preservatives? Problems of selection of preservatives.

Evaluation of preservatives:

1. To assess the number of viable number or microbes in the final product as in function of

time.

2. To assess the quantities of preservatives compound at specific interval of time.

Problems of selection of preservatives:

1. The problem of selection of preservatives for emulsion systems is unique.

2. It is desirable to have a compound which distributes to a large extent in the aqueous

phase. At the same time the preservatives compound must have a tendency to get

concentrated in the lipids of microbial cell in preference to remaining in the aqueous

phase.

Q. Write on about benzoic acid & benzoate, parahydroxybenzoates, phenyl mercuric

nitrate & other salt, phenol, dichlorophen, formaldehyde.

Benzoic acid and benzoates

1. Simple aromatic acid.

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

3. Concentration 0.1%.

Salicylic acid and salicylates

Use as sodium salicylate for enfant of 1 part to 1000.

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.


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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.

Antioxidant

Antioxidant: An antioxidant is a substance which is 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 its affording protection to other oxygen sensitive drug.

Function of anti-oxidant: Used to control oxidation of-

API

Preservative, e.g. potassium sorbate

Vehicle, e.g. oils or fats susceptible to β-oxidation (rancidification)

Colourants (ageing discolouration)

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 containg Substance:

Cysteine Hydrochloride

5. Monohydric Phenol:

Thymol

Concentration of antioxidant in formulation: 0.001 – 0.1%

Classification of antioxidant:

1. On the basis of the function antioxidants are 2 types. They are,

a. Primary antioxidant/ true antioxidant.

b. Synergist.

a. Primary antioxidant: Primary antioxidants act by interfering with the propagation step

of autoxidaton process.

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

hydroxyl tolune (BHT) and nordihydroguaiaretic acid (NDGA).


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b. Synergist: The synergist class of antioxidants has little inherent antioxidal properties.

However, when used in conjugation with a primary antioxidant they have the ability

greatly to enhance antioxidant efficiency. e.g.,

1. Water Soluble:

Citric Acid

Tartaric Acid

Phosphoric Acid

Ascorbic Acid (having antioxidant

property)

2. Oil Soluble:

Ascorbyl Palmitate

Mono-isopropyl

Citrate

Palmityl Phosphate

Mono-stearyl Citrate

2. On the basis of the source antioxidants are 2 types. They are,

a. Natural antioxidants.

b. Synergist antioxidant.

a. Natural antioxidant: These exist and available in nature.

e.g., Tocopherol (Vitamin E), Sesamol, Guaiac resin, Mehionine.

b. Synthetic antioxidant: These are isolated by synthesis by an artificial mean.

i.e Butylated hydroxyl anisol (BHA), Butylated hydroxyl tolune (BHT), Tertiary butyl

hydroquinone.

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

a. Water soluble antioxidant.

b. Oil soluble antioxidant.

a. Water soluble antioxidant: The main classes of water soluble antioxidants are sulfurous

acid salt, ascorbic acid isomers and thhiol derivatives.

Compound Drug for which suitable

Sodium Metabisulfite

1. Steroids.

2. Antibiotics.

3. Adrenergic.

4. Procainaonid.

5. Morphine.

b. Oil soluble antioxidant: The oil soluble antioxidants are often needed for the protection

of fatly food and osmotic.

Compound Material for which suitable

BHA and BHT Fatty formulation.

Properties of Antioxidants:

1. An ideal antioxidant should be stable.

2. Effective at a low, nontoxic concentration.

3. It should not posses objectionable color, odor and taste.

4. It should be nontoxic, nonirritant and form no harmful products.

5. It should be thermostable.

6. It should be readily soluble or dispersible in the medium.

7. Soluble at the required concentration.

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

9. Stable and effective under normal conditions of use, over a wide pH and temperature range.

10. Compatible with a wide variety of drugs and pharmaceutical excipients.

11. It should be neutral and should not react chemically with other constituents present.

12. Colorless in both the original and oxidized form.

13. Nontoxic both internally and externally at the required concentration.

14. Reasonable cost.

15. Unreactive (does not adsorb, penetrate, or interact) with containers or closures.


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Mode of action: Anti-oxidants act by-

1. By acting as a reducing agent.

2. By acting as free radical inhibitor to block the oxidative chain reaction.

3. By acting as synergist increasing the efficiency of antioxidant.

4. By acting a chelating agent such as EDTA salt. This salt complex with metal ion which

catalyze the oxidative reaction.

Q. Define oxidation, auto-oxidation, and pre-oxidants.

Oxidation: Oxidation is defined as loss of electrons or addition of oxygen.

Auto-oxidation: It is a reaction with oxygen of air which occurs spontaneously without other

factors.

Pre-oxidants: These are substances catalyze oxidation process e.g., metals, some impurities.

Q. Write down the chemical groups which undergo oxidation.

Chemical groups which undergo oxidation:

1. Phenolic compounds: Phenylephrine.

2. Catechol derivatives: Adrenaline and noradrenaline.

3. Some antibiotics: Tetracyclines.

4. Oils (fixed and volatile).

5. Vitamins (lipid and water soluble).

Q. How to evaluate oxidation in pharmaceutical agent form?

By monitoring the following objective we can identify oxidation.

1. Change of color, odor, and viscosity of screening/ pharmaceutical agents.

2. For fixed and volatile oils: change of color, taste, odor, and viscosity

Q. How you can protect pharmaceutical from oxidation?

Protection of drugs from oxidation:

1. Addition of Antioxidants: Vitamin E, vitamin C and inorganic sulfur compounds,

thiosulfate and polysulfide.

2. Addition of chemicals which form complexes with metals e.g., EDTA, Benzalkonium

chloride

3. Protection from light:

a. Using of dark container.

b. Storage in dark places.

c. Packaging with substances which absorbed light e.g., Oxybenzene.

4. Choice of suitable pharmaceutical dosage forms which reduce the possibility of oxidation

process (solid dosage forms are better than solutions).

5. Maintenance of pH by using buffer solution.

6. Choice of suitable solvent (rather than water).

7. Storage in low temperature.

8. Protection from air by:

a. Using good closed containers.

b. Replacement of oxygen by nitrogen.


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Q. Mention 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

Sweetening agents

Sweetening agents are employed in liquid formulations designed for oral administration

specifically to increase the palatability of the therapeutic agent.

Example: Sucrouse, Lactose, Saccarine, Aspertame, Sorbitol, Mannitol etc.

Uses of sweetening agent:

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.

In anthelmintic and multivitamin tablets sweeting agents are used.

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.

Flavoring Agents

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.


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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 days 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.

Coloring and Opacifying Agent

Coloring agents are pharmaceutical ingredients that impart the preferred color to the formulation.

The function of these ingredients is to enhance the product quality. They provide-

1. Product identification.

2. Protect the core from light and moisture.

3. They increase the solid concentration with any impact on viscosity thus reducing the drying

time.

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 color is required concentration is more than 2%.

Example:

White: Titanium dioxide

Blue : Brilliant blue ,Indigo carmine

Red : Amaranth Carmine

Yellow: saffron

Green

Brown: caramel

Dyes are soluble forms of a particular color. They go into solution and can result in very deep, vibrant

colors and therefore used in liquid products. The most common colorants used are FD&C or D&C

certified, these are either dyes or lakes of dyes.

FDC red-2 Amaranth

FDC green -3 Green

FDC green -4 Erithrosine

FDC yellow-5&6 Tartrasine

FDC blue-1 Brilliant blue

FDC blue-2 Indigo

Lakes are dyes that undergo a processing step that adheres them onto insoluble substrates. Since lake

contain less colorant so required in larger concentration in solution. Lakes are used in chewable

products and coating solutions for tablets. e.g., aluminum or calcium salts, iron oxide, anthrocyanins,

caramel, carotenoids, chlorophyll, indigo, flavones, turmeric acid and carminic acid.

Opacifiers are used to give more pastel color and increase film coverage. These can provide white

coat or mask the color of the tablet core. These are mostly inorganic material. The substances

employed are- Titanium dioxide (Most Common), Talc, Aluminum silicate, Magnesium carbonate,

Calcium sulfate, Aluminum hydroxide


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Ointment Bases

Q. Define ointment bases and mention its ideal properties.

Ointment Bases: 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:

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 and non-irritating.

6. It should be 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.

Q. Classify ointment base.

The ointment bases are classified as follows:

1. Oleaginous bases

2. Absorption bases

3. Emulsion bases

4. Water soluble bases.

Q. Describe oleaginous base with its disadvantage

Oleaginous Bases: These bases consist of water insoluble hydrophobic 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. The oleaginous bases are decreasing in favour due to the reasons described

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.

Q. Briefly describe hydrocarbon bases.

Hydrocarbon Bases

1. 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.


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2. 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.

3. 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.

Q. Briefly describe absorption base. Give its advantage and disadvantage.

Absorption Bases: 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. The following are some of the absorption bases used.

1. Wool Fat:

a. It is also known as anhydrous lanolin.

b. It is the purified anhydrous fat like substance obtained from the wool of sheep.

c. It is practically insoluble in water but can absorb about 50% of its weight of water.

d. 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.

2. Hydrous Wool Fat:

a. It is also known as lanolin.

b. It is the purified fat like substance obtained from wool of sheep.

c. It is a yellowish white ointment like mass with characteristic odour.

d. It is insoluble in water but soluble in ether and chloroform.

3. Wool Alcohol:

a. It is obtained from wool fat by treating it with alkali and separating the fraction

containing cholesterol and other alcohols.

b. It contains not less than 30% of cholesterol.

c. It is used as an emulsifying agent for the preparation of water in oil emulsions and is used

to absorb water in ointment bases.

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

emulsions.

4. Bees Wax:

a. It is purified wax obtained from the honeycomb of bees.

b. It is of two types: (a) yellow bees wax and (b) white bees wax obtained by bleaching and

purifying the yellow bees wax.

c. Bees wax is used as a stiffening agent in pastes, ointments and other preparations.

5. Cholesterol:

a. It is widely distributed in animal organisms.

b. 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.

Disadvantages of Absorption Bases

1. These bases possess the undesirable property of greasiness.


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Q. Write a short note on i. Emulsion and ii. Water absorption base.

i. 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. 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.

ii. 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.

Q. Define carbowaxes wits its ideal properties.

Carbowaxes: Water soluble bases consist of water soluble ingredients such as polyethylene

glycol polymers which are popularly known as carbowaxes.

Ideal properties of Carbowaxes:

1. Carbowaxes are water soluble.

2. They are non-volatile.

3. They are inert substances.

4. They do not hydrolyse and do not support the bacterial or mold growth.

5. The release of medicament is rapid.

6. A blend of different carbowaxes is used to get an ointment of desired consistency.

Q. Mention the factor governing selection of an ideal ointment base.

Factors Governing Selection of an Ideal Ointment Base: The factors which may help in the

selection of an ideal ointment base are discussed below:

1. Dermatological factors.

2. Pharmaceutical factors.

1. Dermatological Factors

a. Absorption and Penetration: The word 'absorption' means actual entry into the blood

stream, i.e. systemic absorption whereas 'penetration' means transference through the skin, i.e,

cutaneous penetration.

Various experiments have been conducted by a number of scientists to study the problems of

absorption and penetration which may be summarized as follows:

i. Only the ointment base penetrates deep into the tissues of the skin.

ii. It is mainly medicament which is absorbed into the blood stream.

iii. Paraffins do not readily penetrate the skin whereas animal and vegetable fats and oils

normally penetrate the skin. Animal fats, e.g. lard and wool fat when combined with

water, penetrates the skin.

iv. Substances which are soluble both in oil and water are most readily absorbed.

v. Water soluble substances are more readily absorbed from water soluble bases.

vi. O/W emulsion bases release the medicament more readily than greasy bases or W/O

emulsion bases.


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b. Effect on Skin Function: Greasy bases interfere with normal skin functions, i.e. heat

radiation and sweat. 'They are irritant to the skin. O/W emulsion bases and other water miscible bases

produce a cooling effect rather than heating effect and mix readily with skin secretions.

c. Miscibility with Skin Secretions and Serum: Skin secretions are more readily miscible with

emulsion bases than with greasy bases. Due to this miscibility the drug is more rapidly and completely

released to the skin hence lesser proportion of the medicament rs required when such bases are used.

O/W emulsion bases are more readily miscible with serum from broken skin therefore they are

particularly useful in weeping eczema.

d. Compatibility with Skin Secretions: The bases used should be compatible with skin

secretions and should have a pH about 5.5 because the average pH of the skin secretions is around 5.5.

Generally neutral ointment bases are preferred.

e. Freedom from Irritant Effect: Ointment bases used should be free from irritant effect on the

skin. All bases used should be of high standard of purity and bases used specially for eye ointments

should be non-irritating and free from foreign particles.

f. Emollient Properties: Dryness and brittleness of the skin causes discomfort to the skin

therefore the bases used should possess emollient properties that they should be able to keep the skin

moist. For this purpose water and humectants such as glycerin and propylene glycol are used.

Ointments containing wool fat, lard and liquid paraffin also act as emollients by preventing rapid loss

of moisture from the skin.

g. Ease of Application and Removal: The ointment bases used should be easily applicable as

well as easily removable from the skin. Stiff and sticky ointments are not suitable as they may cause

damage to the newly formed tissues of the skin. Therefore emulsion bases are more preferred as they

are softer and spread more readily over the area to which they are applied. They can be easily

removed by simply washing with water.

2. Pharmaceutical Factors

a. Stability: Fats and oils obtained from animal and vegetable sources are liable to undergo

oxidation unless they are suitably preserved. Lard, an animal fat used to be a common ingredient of

ointment) but it is rarely used now a days because it easily gets rancid. Soft paraffin, simple ointment

and paraffin ointment are inert and stable. Liquid paraffin is also stable but on prolonged storage it

gets oxidized therefore an antioxidant like tocopherol may be incorporated. Emulsions prepared with

wool fat are liable to surface discolouration. O/W type emulsion bases provide a good medium for

growth of microorganisms, therefore must be suitably preserved.

b. Solvent Properties: Most of the medicaments used in the preparation of ointments are

insoluble in the ointment bases therefore they are finely powdered and distributed uniformly

throughout the base. Phenol, if dispersed in finely powdered state may cause blisters therefore it must

be dispersed in a suitable base which should keep the phenol in solution form. Hence a base

consisting of a mixture of hard paraffin, soft paraffins, bees wax and lard is used for this purpose.

Similarly in the case of compound mercury ointment, olive oil is used to keep the camphor in solution

form.

c. Emulsifying Properties: Hydrocarbon bases can absorb only a small amount of aqueous

substances whereas some animal fats can absorb an appreciable amount of water, e.g. wool fat can

take up about 50% of water, and when mixed with other fats can take up several times its own weight

of aqueous or hydroalcoholic liquids. Hence wool fat is included in the base for eye ointments.

Emulsifying ointment, cetrimide emulsifying ointment and cetomacrogol emulsifying ointment

are capable of absorbing considerable amount of water, forming oil in water creams.

d. Consistency: The ointments produced should be of suitable consistency. They should neither

be too hard nor too soft. They should withstand the climatic conditions. Thus in summer they should

not become too soft and in winter not too hard to be difficult to remove from the container and spread

on the skin.


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Coating Agent

Coating is a process by which an essentially dry, outer layer of coating material is applied to the

surface of a dosage form and agents which are used in this coating process is called coating agents.

Similar to taste masking technology, the first coatings were solutions of sucrose (12–20%). Once

polymers were discovered and understood, they were applied in low concentrations (1–3%) using

organic solvents. Current technology uses polymers manufactured as latex or pseudo-latex dispersions

to avoid the use of organic solvents. Depending on the application, aesthetic or functional coating, the

use levels can range from 2 to 20% of the weight of the material being coated.

Types: Three types of coating agents are used pharmaceutically,

1. Film coating.

2. Sugar coating.

3. Compression coating.

Function of coating agents: 1. To improve appearance: often where the core tablet is of poor colour or shows mottling.

2. Protection from environmental conditions: Some of the ingredients may not be stable in the

presence of moisture, light, oxygen etc. The product stability can be improved by coating.

3. Taste masking: Mask the bitter or unpleasant taste.

4. Odour masking: Mask the unpleasant odour of active ingredients like vitamins, antibiotics

etc.

5. Change in appearance: To impart colour for easy identification during manufacture,

dispensing, in use by patient and brand image building.

6. Ease of swallowing

Examples: Excipients, Carboxymethyl cellulose sodium (CMC), Carnauba Wax, Cellulose acetate,

phthalate (CAP), Ethylcellulose, Gelatin, Hydroxypropyl cellulose (HPC), Hypromellose (HPMC),

Maltodextrin, Methylcellulose, Starch, Sucrose, Zein.

Sorbents

Sorbents are materials that soak up oil from the water.

Types and examples of sorbents:

• Natural sorbents- peat moss, sawdust, feathers, and anything else natural that contains carbon.

• Synthetic sorbents- polyethylene and nylon etc..

Functions of sorbents: Sorbent are used for tablet/capsule moisture-proofing by limited fluid sorbing

(taking up of a liquid or a gas either by adsorption or by adsorption) in a dry state.

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.

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.


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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.

Solvent 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.

Example and uses of solvent • 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:

Lack of toxicity, physiological compatibility, and good solubilising power (high dielectric

constant), but

Likely to cause instability of hydrolytically unstable drugs

Good vehicle for microbial growth

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


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Chelating agent 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” are substances 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.

Example and 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.

Buffering agent

These are materials which, when dissolved in solvent will enable the solution to resist any change

in pH should an acid or an alkali be added. The choice of suitable buffer depends on the pH and

buffering capacity required.

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

product. Interaction of the product with container component and dissolution or loss of gases vapours.

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)

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

Buffer system with concentration:

Name of buffer System Concentration

Acetate CH3COOH + CH3COONa 1-2%

Citrate Citric acid + Na-citrate 1-3%

Phosphate H3PO4 + Hs salt 0.8-2%

Carbonate H2CO3 + NaHCO3 1-2%

Features of buffering agent:

• It should have a low toxicity.

• It should be buffered at the range of 7.4 as the pH of the body is 7.4.

• It should be non-irritant.

Examples of buffering agent: Most of the buffering system are based on carbonate, citrates,

gluconates , lactates, phosphates, or tartrates etc.


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Surfactants

Surfactants are compounds that lower the surface tension (or interfacial tension) between two

liquids or between a liquid and a solid and increase the solubility. They are also known as surface

active agents.

They may be used as emulsifying agents, detergents, solubilising agents, wetting agents, foaming

agents. antifoarning agents, flocculating agents and deflocculating agents.

Properties of surfactants: A surfactant must fulfill 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: 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)

Sodium lauryl sulphate - It is used as an excipient on some dissolvable aspirins and other

fiber therapy caplets.

2. Cationic surfactant (here hydrophilic region is positively charged i.e. a cation)

Cetyl trimethyl ammonium bromide (cetrimide) - is an effective antiseptic agent against

bacteria and fungi.

3. Non-ionic surfactants :

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 :

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.

Q. Write down 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 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 agent 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.

Q. Define micelle and CMC.

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.


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Q. Elucidate 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.

Viscosity imparting agents

Viscosity imparting agents: These agents are used when it is desirable to increase or decrease the

viscosity of a liquid either to serve as adjacent for palatability or to improve pour ability. They are

also called thickening agents.

Some viscosifiers go into solution, such as certain cellulose based polymers, resulting in a Newtonian-

type viscosity. Other materials increase viscosity, while imparting a yield stress to the

suspension. This type of product is known as thixotrope.

Viscosity imparting agents are of two types:

1. Viscosity modifier-Viscosity modifiers decrease the viscosity of a liquid to improve pour

ability and make it more palatable.

2. Viscosity enhancer- Viscosity enhancers increase the viscosity of a liquid to improve pour

ability and make it more palatable.

Most commonly used viscosity imparting agents are: Acacia, Agar, Sodium alginate, Bentonite,

Carbomer, Carboxymethyl cellulose sodium (CMC), Guar gum, Hydroxypropyl cellulose (HPC),

Hypromellose (HPMC), Methylcellulose, Pectin, Hydroxyethylcellulose, Polyvinyl alcohol (PVA),

Polyvinylpyrrolidone (PVP)

Humectant

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

desiccant. They are used in many products including food, cosmetics, medicines and pesticides.

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 colorless or not of too intense color.


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3. It should have good odor and taste.

4. It should be nontoxic and nonirritant.

5. It should be noncorrosive to packaging materials

6. It should not solidify under normal conditions.

7. It should not be too costly.

Classification of humectants with examples: 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 vapor 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 vapor onto the surface, as a layer of film.

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

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

Wetting Agents

To aid ‘wetting’ and dispersion of a hydrophobic API, preservative or antioxidant

Reduce interfacial tension between solid and liquid during manufacture or reconstitution of a

suspension

Not all are suitable for oral administration

Examples include:

Surface active agents, e.g.

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

• Parenteral: polysorbates, poloxamers, lecithin

• External: sodium lauryl sulphate

But these can cause excessive foaming (see anti-foaming agents) 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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Anti-Foaming Agent

Q. Define anti-foaming agent with examples.

Anti-foaming: A defoamer or an anti-foaming agent is a chemical additive that reduces and

hinders the formation of foam in industrial process liquids by reducing interfacial tension between

two phases.

Example: Insoluble oils. polydimethylsiloxanes and other silicones, certain alcohols, stearates

and glycols, Simethicone (polydimethylsiloxane-silicon dioxide).

Q. Why anti-foaming agents are used in industrial process?

In industrial processes, foams pose serious problems. They cause defects on surface coatings.

They prevent the efficient filling of containers. So, anti-foaming agents are used in industrial process

to prevent formation of foams.

Q. Write down the properties of an anti-foaming agent.

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.

Q. Write down the classification of anti-foaming agents.

Classification of anti-foaming agents: Anti-foaming agents are classified into the following

types.

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

Q. Write down the applications of anti-foaming agents.

Applications of anti-foaming agents:

1. Detergents: Anti-foams are added in certain types of detergents to reduce foaming that might

decrease the action of the detergent. For example dishwasher detergents have to be low foaming for

the dishwasher to work properly.


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2. Food: When used as an ingredient in food, antifoaming agents are intended to curb effusion

or effervescence in preparation or serving. The agents are included in a variety of foods such as

chicken nuggets in the form of polydimethylsiloxane (a type of silicone). Silicone oil is also added to

cooking oil to prevent foaming in deep-frying.

3. Industrial use: Defoamers are used in many industrial processes and products: wood pulp,

paper, paint, industrial wastewater treatment, food processing, oil drilling, machine tool industry, oils

cutting tools, hydraulics etc.

4. Pharmaceuticals: Antifoaming agents are also sold commercially to relieve bloating. A

familiar example is the drug Simethicone, which is the active ingredient in drugs such as Entacyd

plus.

Plasticizer

Q. Define plasticizer. Why plasticizer needed for film coating?

Plasticizer: Plasticizers lower the glass transition temperature of polymers, specifically polymers

used for coatings. By lowering the glass transition temperature, the polymers can partially melt, and

the droplets can coalesce to form a completely sealed coating on a tablet or spheroid at a lower

temperature, thus, preventing the active from being exposed to elevated processing temperatures. This

affords better, more consistent release of the active. e.g.,

Commonly used plasticizers are Glycerin, Propylene Glycol, Triacetin, Triethanolamine, castor

oil, PG, Glycerin, lower molecular weight (200- 400 series), PEG, surfactants etc. For aqueous

coating PEG and PG are more used while castor oil and spans me primarily used for organic-solvent

based coating solution. External plasticizer should he soluble in the solvent system used for dissolving

the film former and plasticizer.

Recommended levels of plasticizers range from 1-50% by weight of the film former. Plasticizers

are normally used at concentration between 15-35% based on polymer weight. .

Plasticizer need for film coating because

1. Plasticizers are low molecular weight organic solvents with high boiling points. They are

used to alter the physical properties of a polymer (i.e. hard or brittle) and render it more

flexible and softer to function as a film-coating material.

2. Plasticizers also have a significant influence on mechanical properties of the film.

3. Specifically, they can reduce cohesive intermolecular forces along the polymer chains and

enhance flexibility by increasing strain or film elongation and decreasing tensile strength

and elastic modulus of the polymer.

4. Additionally, they influence the permeability characteristics of the film, especially to

water vapor, as well as lowering the glass transition temperature of the polymer to allow

a more feasible coaling process.

5. Plasticizers also possess solvent power to insure compatibility with the polymer.

6. Plasticization time (i.e. mixing time of plasticizer with polymer) and plasticizer level

influence the nature of the polymer films.

Q. Classify plasticizer.

Types of plasticizers: Three types of plasticizers are commonly used in pharmaceutical coating

processes:

a. Polyols: Water miscible

1. Glycerol (glycerin)

2. Propylene glycol (PG)

3. Polyethylene glycol (PEG 200-6000 grades)


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b. Organic esters:

1. Diethyl phthalate (DEP) – water insoluble

2. Dibutyl phthalate (DBP) - water insoluble

3. Dibutyl sebacate (DBS) – water insoluble

4. Triethyl citrate (TEC) - water miscible

5. Acetyltriethyl citrate ( ATEC) - water insoluble

c. Oils/glycerides: water insoluble

1. Castor oil

2. Distilled acetylated monoglycerides

3. Fractionated coconut oil

Tonicity contributors

Q. What do you mean by tonicity contributors? Give example with used concentration.

Tonicity contributors: Tonicity contributors are the substances which are often included in

parenteral product particularly in large volume preparation to make it isotonic with blood or other

body fluid.

Commonly used tonicity contributor

Name Concentration Name Concentration

1. NaCl 0.9% 2. Lactose 5.0%

3. Dextrose 5.5% 4. Glycerine 2.25%

5. Mannitol 2.5%

Q. Why tonicity contributors are used in pharmaceutical formulation?

The compound which are used as tonicity contributors, reduce the pain at the site of injection.

Adjustment of tonicity to isotonic condition is important, inorder to prevent the integrity of RBC by

the addition of NaCl, Borax etc.

Q. Define hypertonic, hypotonic and isotonic solution.

Isotonic solution: The solutions that have same osmolarity to the blood or other body fluid are

known as isotonic solution. i.e. 0.9% solution of sodium chloride is isotonic with plasma.

Hypotonic solution: The solutions that have low osmolarity than the blood or other body fluid

are known as hypotonic solution. i.e. 0.45% solution of sodium chloride hypotonic with plasma.

Hypertonic solution: The solutions that have high osmolarity than the blood or other body fluid

are known as hypertonic solution. i.e. 5% solution of sodium chloride hypertonic with plasma.

Q. Problem with hypertonic and hypotonic solution in human body.

The solutions which are not isotonic with plasma may be harmful to use. On injecting the

hypotonic solutions into blood stream. It may enter the red blood cells in an attempt to produce

equilibrium. The cells swell rapidly until they burst leading to haemolysis. As this damage is

irreversible it may lead to serious danger to red blood cells.

When hypertonic solution is injected into the blood stream, the water comes out of the membrane

of red blood cells in order to reach equilibrium. The cells shrink leading to crenulation which is only a

temporary damage. When the osmotic pressure of two solutions becomes equal the damaged cells will

come to their original position. Hence hypertonic solutions may therefore be administered without

permanent damage to the blood cells. They should be injected slowly to ensure rapid dilution into the

blood stream and to minimize the crenulation of blood cells


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Q. Write down the general principle for adjustment to tonicity and problems.

General principle for adjustment to tonicity:

Calculations for solutions iso-osmotic with blood and tear: There are generally two methods

for adjustment of tonicity. These ares-

1. Based on freezing-point data.

2. Based on molecular concentration.

1. Based on freezing-point data:

0.52 − 𝑎

𝑏

Where,

a = Freezing-point of unadjusted solution.

b = Freezing-point of a 1% w/v solution of

the adjusting substance.

2. Based on molecular concentration:

i. For non-ionising solute

𝑊 = 0.3𝑀

ii. For ionising solute

𝑊 =0.3𝑀

𝑁

Where,

W = Concentration required in g per liter.

M = Molecular weight of the

N = Number of ion produce from each

molecule of the solute assuming that

dissociation is completed

Problem 1: What concentration of Procain Hydrochloride will yield a solution iso-osmotic with

blood plasma?

Ans: Freezing point of 1% w/v solution of Procain Hydrochloride is -0.122°C

∴ Precentage w v⁄ of Procain Hydrochloride required =0.52 − 0.00

0.122= 4.26% w v⁄

Problem 2: Find the concentration of sodium chloride required to prepare a 1% solution of

Cocaine Hydrochloride iso-osmotic with blood plasma.

Ans: Freezing point of a 1% w/v solution of Cocaine Hydrochloride is -0.09°C and that of 1%

w/v solution of sodium chloride is -0.576°C.

∴ Precentage w v⁄ of sodium chloride required =0.52 − 0.09

0.576= 0.746% w v⁄

Problem 3: Find the concentration of sodium chloride required to render a 1.5% solution of

Procaine Hydrochloride iso-osmotic with blood plasma.

Ans: Freezing point of a 1% w/v solution of procaine Hydrochloride is -0.122°C and that of 1%

w/v solution of sodium chloride is -0.576°C.

∴ Precentage w v⁄ of sodium chloride required =0.52 − (0.122 × 1.5)

0.576= 0.585% w v⁄

Problem 4: Find the concentration of anhydrous dextrose needed to produce a solution iso-

osmotic with blood plasma.

Ans: The molecular weight of dextrose is 180 and it is non-ionising.

∴ 0.3 × 180 = 54 g per litre is required (The B. P. uses 5%)

Problem 5: Find the concentration of boric acid required to produce a solution iso-osmotic with

lachrymal secretion.

Ans: The molecular weight of boric acid is 62 and it is a partially non-ionising.

∴ 0.3 × 62 = 18.6 g per litre (1.86% w v)⁄


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Formula Nomenclature

CCl3F CFC-11

CCl2F2 CFC-12

C2Cl2F4 CFC-114

Problem 6: Find the concentration of sodium chloride required to produce a solution iso-osmotic

with blood plasma.

Ans: The molecular weight of sodium chloride is 58.8 and it dissociates into 2 ions.

∴0.3 × 58.5

2= 8.8 g per litre (0.88% w v)⁄

(The B. P. uses 0.90%)

Propellants

Q. Define aerosol with its composition and give its purpose of use.

Aerosol: An aerosol or pressurized package is defined as "a system that depends on the power of

a compressed or liquefied gas to expel the contents from the container."

Composition:

1. Product concentrates: i. Active ingredient. ii. Surface active agents. iii. Antioxidant.

2. Propellant.

An examination of the aerosol dosage form reveals the following specific advantages over other

dosage forms:

1. A dose can be removed without contamination of remaining material. Stability is

enhanced for those substances adversely affected by oxygen and/or moisture. When

sterility is an important factor, it can be maintained while a dose is being dispensed.

2. The medication can be delivered directly to the affected area in a desired form, such as

spray, stream, quick-breaking foam, or stable foam.

3. Irritation produced by the mechanical application of topical medication is reduced or

eliminated.

Other advantages are ease and convenience of application and application of medication

in a thin layer.

Q. What do you mean by propellants and classify it.

Propellant: Propellants are the substances which are used for aerosol preparation to exert/ create

vapour pressure.

i.e.

1. HFA: HFA-227, HFA-134a

2. CFC: CFC-11, CFC-12, CFC-114

3. Compressed gas: Nitrogen, argon.

Classification of propellants: The propellants used in aerosol system may be classified into

1. Liquified gases: a. Fluorinated hydrocarbons

b. Hydrocarbons

2. Compressed gases: a. Insoluble in water, i.e. nitrogen, argon, and

b. Soluble in water, i.e. carbon dioxide,

nitrous oxide.

Q. Write down the nomenclature of CFC and HFA.

CFCs and HFAs are numbered using a universal system.

1. The first digit is the number of carbon atoms minus 1 (omitted if zero).

2. The second is the number of hydrogen atoms plus 1.

3. The third is the number of fluorine atoms.

Chlorine fills any remaining valencies, given the total number of atoms required to saturate the

compound. If asymmetry is possible, this is designated by a letter.

i.e.


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Q. Briefly describe Raoult’s law of vapour pressure.

Raoult's Law: The vapour pressure of a mixed system is equal to the sum of the mole fraction of

each, component multiplied by its vapour pressure.

P = Pa + Pb

Where P is the total vapour pressure of the system and Pa and Pb are the partial vapour pressures

of the components, a and b.

Pa = 𝑥aPa0

Pb = 𝑥bPb0

Where xa and xb are the mole fractions and Pa0 and Pb

0 are the vapour pressures of components a

and b, respectively.

Q. Why use of CFCs as propellant decreased day by day than HFAs.

CFCs are friendly to ozone in the earth's stratosphere. The reaction of CFCs with the ozone in the

earth's stratosphere, which absorbs ultraviolet radiation at 300 nm, and their contribution to global

warming are major environmental concerns. CFCs pass to the stratosphere, where in the presence of

UV they liberate chlorine, which reacts with ozone. The depletion of stratospheric ozone results in

increased exposure to the UV-B part of the UV spectrum, resulting in a number of adverse effects, in

particular an increased incidence of skin cancer. The Montreal Protocol of 1987 was a global ban on

the production of the five worst ozone-depleting CFCs by the year 2000, This was amended in 1992,

so that production of CFCs in developed countries was phased out by January 1996. In the European

Union, all ozonedepleting CFCs were banned by the end of 1995.

HFAs are friendly to ozone in the earth’s stratosphere and do not cause such complication like

CFCs.

This is the reason that the use of CFCs as propellant decreased day by day than HFAs.

Desiccant

Q. Define desiccant with examples.

Desiccant: A desiccant is a hygroscopic substance that induces or sustains a state of dryness

(desiccation) in its vicinity. Commonly encountered pre-packaged desiccants are solids that absorb

water. Desiccants for specialized purposes may be in forms other than solid and may work through

other principles, such as chemical bonding of water molecules. They are commonly encountered in

foods to retain crispness. Industrially, desiccants are widely used to control the level of water in gas

streams.

The most common desiccant is silica, an otherwise inert, nontoxic, water-insoluble white solid.

Tens of thousands of tons are produced annually for this purpose. Other desiccants include activated

charcoal, calcium sulfate, calcium chloride, and molecular sieves (typically, zeolites).

Why silica is used as desiccant in pharmaceutical industry?

Q. How can you measure the efficiency of a desiccant?

Performance efficiency

One measure of desiccant efficiency is the ratio (or precentage) of water storable in the desiccant

relative to the mass of desiccant.

Another measure is the residual relative humidity of the air or other fluid being dried.

The performance of any desiccant varies with temperature and both relative humidity and

absolute humidity. To some extent, desiccant performance can be precisely described, but most

commonly, the final choice of which desiccant best suits a given situation, how much of it to use and

in what form, is made based on testing and practical experience.


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Q. Write down the applications of desiccant.

Applications of desiccant:

1. It is used in the manufacture of insulated windows where zeolite spheroids fil a rectangular

spacer tube at the perimeter of the panes of glass. The desiccant helps to prevent the condensation of

moisture between the panes. Another use of zeolites is in the dryer component of air conditioning

systems to help maintain the efficacy of the refrigerant. Desiccants are also commonly used to protect

goods in shipping containers against moisture damage. Hygroscopic cargo, such as cocoa, coffee and

various nuts and grains are particularly susceptible to mold and rot when exposed to condensation and

humidity. Because of this, shippers often take precautionary measures to protect against cargo loss.

2. Desiccants induce dryness in any environment and reduce the amount of moisture present in

air. Desiccants come in various forms and have found widespread use in the food, pharmaceuticals,

packing, electronics and many manufacturing industries.

3. Drying of solvents: Toluene is refluxed with sodium and benzophenone to produce dry,

oxygen free toluene. The toluene is dry and oxygen free when the intense blue coloration from the

benzophenone ketyl radical is observed.

4. Desiccants are also used to remove water from solvent typically required by chemical

reactions that do not tolerate water, e.g., the Grignard reaction. The method generally, though not

always. involves mixing the solvent with the solid desiccant. The dried solvent is then separated by

the desiccant by filtration or distillation.

Acidifying agents

Acidifying agents will lower the pH of the solution. They are typically derived from phosphoric

acid or blends of phosphate ester anionic surfactants containing free phosphoric acid. Their primary

use is with insecticides when there is a need to prevent alkaline hydrolysis by lowering pH of the

spray solution

Urinary Acidifying Agents

1. Citric acid

2. Magnesium carbonate

3. Potassium acid phosphate

4. Renacidin

Alkalinizing agent

Alkalinizing agents are drugs used to manage disorders associated with low pH. For example,

they may be used to treat acidosis due to renal failure. Used for oral or parenteral therapy, sodium

bicarbonate is the commonly preferred alkalinizing agent. Others include potassium citrate, calcium

carbonate, sodium lactate and calcium acetate. Alklinizing agent excipients are important in

pharmaceutical formulations where the active pharmaceutical ingredient requires an alkaline

environment for stability or therapeutic effectiveness.

Sodium bicarbonate

Sodium citrate/citric acid

Sodium lactate

Ammonia Solution

Ammonium Carbonate

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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Air Displacement Agents

Air displacement agents: Substances employed to displace air in a hermetically sealed container

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

Anticaking agent

An anticaking agent is an additive placed in powder or granulated materials, such as table salt, to

prevent the formation of lumps and for easing packaging, transport and consumption.

An anticaking agent in salt is denoted in the ingredients, for example, as "anti-caking agent

(554)", which is sodium aluminosilicate, a man-made product. This product is present in many

commercial table salts as well as dried milk, egg mixes, sugar products and flours. In Europe, sodium

ferrocyanide (535) and potassium ferrocyanide (536) are more common anticaking agents in table

salt. Natural anticaking agents used in more expensive table salt include calcium carbonate and

magnesium carbonate.

Some anticaking agents are soluble in water; others are soluble in alcohols or other organic

solvents. They function either by absorbing excess moisture or by coating particles and making them

water repellent. Calcium silicate (CaSiO3) a commonly used anti-caking agent, added to e.g. table salt,

absorbs both water and oil.

Anticaking agents are also used in non-food items such as road salt, fertilizers, cosmetics,

synthetic detergents and in manufacturing applications.

List of anticakiug agents: The following anticaking agents are listed in order by their E number.

E341 tricalcium phosphate

E460(ii) powdered cellulose

E470b magnesium stearate

E500 sodium bicarbonate

E535 sodium ferrocyanide

E536 potassium ferrocyanide

E538 calcium ferrocyanide

E542 bone phosphate

E550 sodium silicate

E551 silicon dioxide

E552 calcium silicate

E553a magnesium trisilicate

E553b talcum powder

E554 sodium aluminosilicate

E555 potassium aluminium silicate

E556 calcium aluminosilicnte

E558 bentonite

E559 aluminium silicate

E570 stearic acid

E900 polydimethylsiloxane

Water repellent

OWR (durable water repellent) is a coating added to fabrics at the factory to make them water-

resistant (or hydrophobic). Most factory-applied treatments are fluoropolymer based. Durable water

repellents are commonly used in conjunction with waterproof breathable fabrics such as Gore-Tex to

prevent the outer layer of fabric from becoming saturated with water. This saturation called 'wetting

out,' can reduce the garment's breathabilitv (moisture transport through the breathable membrane) and


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let water through. As the DWR wears off over time, re-treatment is recommended when necessary.

Many spray-on and wash-in products for treatment of non-waterproof garments and re-treatment of

proofed garments losing their water-repellency are available from sources of sporting apparel. Sprays

are made of Grangers, Nikwax, McNett, Trek7 and others.

Older methods for factory application of DWR treatments involve applying a solution of a

chemical onto the surface of the fabric by spraying or dipping. More recently the chemistry is applied

in the vapor phase using Chemical Vapor Deposition (CVD) machinery. The advantages of CVD

include: (1) It eliminates the use of hazardous and environmentally harmful solvents in the application

process; (2) The process requires less chemical; (3) the waterproof layer is extremely thin and has less

effect on the natural look and feel or the fabric. Later advances have eliminated perfluorinated acids

considered to be potentially hazardous to human health by the US Environmental Protection Agency,

from the application process.

Q. How silicone water repellents work.

Silicone water repellents or waterproofing agents generally come in two forms:

1. Elastomeric polydimethylsiloxanes - elastomeric coatings that adhere to the substrate and

cure to form a flexible, protective membrane.

2. Penetrating water-repellent chemicals- reactive silanes and siloxane resins with

crosslinkable side chains. These materials have smaller molecular structures which enable

them to penetrate deeply into the substrate, where they chemically bond with it.

Either of these materials can be delivered via solvent or aqueous emulsion.

Q. Write a shot note on the following excipient.

a. Acacia

b. Tragacanth

c. Lactose, Monohydrate and Microcrystalline Cellulose

Sialagogues

These materials are usually acidic, and their purpose in a formulation is to stimulate the production of

saliva. They are mostly found in chewable products for children or in gum-based products. By

facilitating the production of saliva, the masticated product is swallowed more readily, limiting the

objectionable flavor of the active from lingering too long.

Example: Citric acid, Fumaric acid, Tartaric acid


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Excepient toxicity

Propylene Glycol Toxicity (Class: Solvent/ preservatives)

Propylene glycol (PG) is a general solvent with anti-microbial properties used in a wide range

of pharmaceutical preparations including oral liquids, topicals and parenteral preparations

However, it’s use in large volumes in children is very much discouraged:

• PG has been associated with cardiovascular, hepatic, respiratory and CNS adverse events,

especially in neonates where the biological half-life is prolonged (~17h) compared with

adults (5h).

• I.V. parenterals containing PG must be infused slowly

• PG also has a laxative action at high oral doses through high osmotic pressure effects.

Ethanol Toxicity (Class: Solvent)

Widely used as a co-solvent to aid solubility

In US, maximum permitted quantities in OTC products:

• <0.5% for children under 6-years

• <5% for children 6-12-years

• <10% for children over 12-years

Acute (overdose) or chronic (long-term use) toxicity is possible

May cause adverse symptoms of intoxication, lethargy, stupor, coma, respiratory depression

and cardiovascular collapse

Peanut Oil Toxicity (Class: Solvent)

Peanut oil is used as a food additive and as a solvent in intra-muscular injections

It has been suggested that the use of peanut oil in childhood (infant formula and topical

preparations) can lead to later episodes of hypersensitivity, and therefore should be

discontinued

Saccharin (Class: Sweetener)

Restricted regulatory acceptability

Poor aftertaste

Hypersensitivity reactions; mainly dermatologic

Paediatrics with allergy to sulphonamides should avoid saccharin

Aspartame Toxicity (Class: Sweetener)

Source of phenylalanine – possibly an issue for phenylketoneurics

Aspartame has been blamed for hyperactivity in children but as yet unproven

Sorbitol (Class: Sweetener)

Can induce diarrhea

Benzyl Alcohol toxicity in neonates (Class: Anti-microbial preservatives)

Widely used as a preservative in cosmetics, foods and pharmaceuticals (including injectables

and oral liquids)

Toxic syndrome observed in neonates – it was attributed to the practice of “flushing out”

umbilical catheters with solutions containing benzyl alcohol (BA), because of trace levels of

benzaldehyde that were present

Dilution of nebulisation solutions with BA-preserved saline led to severe respiratory

complications and even death in neonates. Attributed to accumulation of BA due to an

immature metabolic capability.


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Sodium Benzoate toxicity (Class: Anti-microbial preservatives)

Widely used as a preservative in cosmetics, foods and pharmaceuticals (including injectables

and oral liquids)

Injectable combinations of Na Benzoate and Caffeine should not be used in neonates; found

to elicit non-immunological contact reactions, including urticaria and atopic dermatitis

Limitation on dosing of Na benzoate to neonates - ≤10mg/kg/day – due to immature

metabolic capability

Thimerosal toxicity (Class: Anti-microbial preservatives)

Formerly widely used as a preservative in cosmetics, in soft contact lens solutions and

pharmaceuticals (primarily vaccines)

Being phased out from most paediatric vaccines as better options emerge

Possible links with toxicity in paediatric vaccines, e.g. childhood autism, have been

discounted after much debate

Lactose toxicity (immature metabolism) (Class: Diluents/ Filler)

Lactose occurs widely in dairy products and is used in infant feed formulae.

In pharmaceutical preparations it is widely used as a diluent in tablets and capsules, in

lyophilised powders, as a sweetener in liquid formulations and as a carrier in dry powder

inhalation products.

Lactose intolerance occurs when there is a deficiency in the intestinal enzyme lactase, leading

to GIT build-up of lactose. There is then the risk of abdominal bloating and cramps.

Lactase is normally present at high levels at birth; declining rapidly in early childhood (4-8

years) Hypolactasia (malabsorption of lactose) can thus occur at an early age and,

furthermore, this varies among different ethic groups.

Significant lactose intolerance can also occur in adults but this is rare.


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Use of Different Excipients

Sl. Excipient Use

1 Acacia Emulsifying agent; stabilizing agent; suspending agent; tablet

binder; viscosity-increasing agent

2 Alginate Binder

3 Alginic Acid Stabilizing agent; suspending agent; tablet binder, tablet

disintegrant; viscosity-increasing agent.

4 Aluminum Acetate Antiseptic

5 Benzyl Alcohol Antimicrobial preservative; disinfectant; solvent

6 Butyl Paraben Antimicrobial preservative

7 Butylated Hydroxy Toluene Antioxidant.

8 Citric acid Disintegrant

9 Calcium carbonate Tablet and capsule diluent; therapeutic agent

10 Candelilla wax Binder

11 Croscarmellose sodium Tablet and capsule disintegrant

12 Confectioner sugar Sugar coating adjunct; sweetening agent; tablet and capsule

diluents

13 Colloidal silicone dioxide Adsorbent; anticaking agent; emulsion stabilizer; glidant;

suspending agent; tablet disintegrant; thermal stabilizer;

viscosity-increasing agent. 14 Cellulose Adsorbent; suspending agent; tablet and capsule diluent;

tablet disintegrant.(cellulose microcrystaline) Adsorbent; glidant;

suspending agent;

tablet and capsule diluent; tablet disintegrant (cellulose

powdered) Tablet and capsule diluent.(cellulose Silicified) 15 Plain or anhydrous calcium

phosphate

Diluent

16 Carnuba wax Binder

17 Corn starch Binder

18 Carboxymethylcellulose

calcium

Stabilizing agent; suspending agent;

tablet and capsule disintegrant;

viscosity-increasing agent; water-absorbing agent 19 Calcium stearate Tablet and capsule lubricant

20 Calcium disodium EDTA Chelation

21 Copolyvidone Film-former; granulating agent; tablet binder

22 Castor oil hydrogenated Extended release agent; stiffening agent; tablet and capsule

lubricant

23 Calcium hydrogen phosphate

dihydrate

Diluent

24 Cetylpyridine chloride Antimicrobial preservative; antiseptic;

cationic surfactant; disinfectant;

solubilizing agent; wetting agent 25 Cysteine HCL Reducing Agent

26 Crosspovidone Tablet disintegrant.

27 calcium phosphate di or tri

basic

Tablet and capsule diluent Anticaking agent; buffer, nutrient;

dietary supplement;

glidant; tablet and capsule diluent and clouding agent( for calium

phosphage tribasic)


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Sl. Excipient Use

28 Dibasic Calcium Phosphate Diluent

29 Disodium hydrogen phosphate Buffering agent

30 Dimethicone Antifoaming agent;emollient

31 Erythrosine Sodium Color

32 Ethyl Cellulose Coating agent; flavoring fixative; tablet binder; tablet filler;

viscosity-increasing agent.

33 Gelatin Coating agent; film-former; gelling agent; suspending agent;

tablet binder; viscosity-increasing agent

34 Glyceryl monooleate Nonionic surfactant

35 Glycerin Antimicrobial preservative; emollient; humectant; plasticizer;

solvent; sweetening agent; tonicity agent

36 Glycine Tonicity

37 Glyceryl monostearate Emollient; emulsifying agent; solubilizing agent; stabilizing

agent; sustained-release ingredient; tablet and capsule lubricant

38 Glyceryl behenate Coating agent; tablet binder; tablet and capsule lubricant

39 Hydroxy propyl cellulose Coating agent; emulsifying agent; stabilizing agent; suspending

agent; tablet binder; thickening agent;

viscosity-increasing agent. 40 Hydroxyl propyl methyl

cellulose

Coating agent; film-former; rate-controlling polymer for

sustained release; stabilizing agent; suspending agent; tablet

binder; viscosity-increasing agent.

41 Hypromellose Coating agent; film-former;

rate-controlling polymer for sustained release; stabilizing agent;

suspending agent; tablet binder; viscosity-increasing agent. 42 HPMC Pthalate Coating agent.

43 Iron oxides or ferric oxide Color

44 Iron oxide yellow Color

45 Iron oxide red or ferric oxide Color

46 Lactose hydrous or anhydrous

or monohydrate or spray dried

Binding agent; diluent for dry-powder inhalers; lyophilization

aid;

tablet binder; tablet and capsule diluent.( lactose anhydrous)

Binding agent; diluent for dry-powder inhalers; tablet binder;

tablet and capsule diluent(lactose monhydrate) Binding agent;

diluent for dry-powder inhalations; tablet and capsule diluent;

tablet and capsule filler.(lactose spray dried) 47 Magnesium stearate Tablet and capsule lubricant

48 Microcrystalline cellulose Adsorbent; suspending agent; tablet and capsule diluent; tablet

disintegrant same as cellulose see above it is just that mcc is usp

49 Mannitol Sweetening agent; tablet and capsule diluent; tonicity agent;

vehicle (bulking agent) for lyophilized preparations 50 Methyl cellulose Coating agent; emulsifying agent; suspending agent;

tablet and capsule disintegrant; tablet binder; viscosity-

increasing agent 51 Magnesium carbonate Tablet and capsule diluent

52 Mineral oil Emollient; lubricant; oleaginous vehicle; solvent

53 Methacrylic acid copolymer Coating


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Sl. Excipient Use

54 Magnesium oxide Tablet and capsule diluent

55 Methyl paraben Antimicrobial preservative

56 Povidone or PVP Disintegrant; dissolution aid; suspending agent; tablet binder.

57 PEG Ointment base; plasticizer; solvent; suppository base;

tablet and capsule lubricant

58 Polysorbate 80 solubilizer

59 Propylene glycol Antimicrobial preservative; disinfectant; humectant; plasticizer;

solvent; stabilizer for vitamins; water-miscible cosolvent.

60 Polyethylene oxide Mucoadhesive; tablet binder; thickening agent.

61 Propylene paraben Antimicrobial preservative

62 Polaxamer 407 or 188 or plain Dispersing agent; emulsifying and coemulsifying agent;

solubilizing agent; tablet lubricant; wetting agent.

63 Potassium bicarbonate Alkalizing agent; therapeutic agent

64 Potassium sorbate Antimicrobial preservative

65 Potato starch Binder

66 Phosphoric acid Acidifying agent

67 Polyoxy140 stearate Emulsifying agent; solubilizing agent; wetting agent

68 Sodium starch glycolate Tablet and capsule disintegrant

69 Starch pregelatinized Tablet and capsule diluent; tablet and capsule disintegrant;

tablet binder (starch pregelatinized Glidant; tablet and capsule

diluent; tablet and capsule disintegrant;

tablet binder.( starch , potato, corn , wheat, rice) so check the

above and make the changes

70 Sodium crossmellose Disintegrant

71 Sodium lauryl sulfate Anionic surfactant; detergent; emulsifying agent;

skin penetrant; tablet and capsule lubricant; wetting agent

72 Starch Glidant; tablet and capsule diluent; tablet and capsule

disintegrant;

tablet binder.( starch , potato, corn , wheat, rice) combine all the

starches

73 Silicon dioxide Same as colloidal silicon dioxide

74 Sodium benzoate Antimicrobial preservative; tablet and capsule lubricant

75 Stearic acid Emulsifying agent; solubilizing agent; tablet and capsule

lubricant.

76 Sucrose Base for medicated confectionery; granulating agent;

sugar coating adjunct; suspending agent; sweetening agent;

tablet and capsule diluent; viscosity-increasing agent.

77 Sorbic acid Antimicrobial preservative

78 Sodium carbonate Carbonating agent

79 Saccharin sodium Sweetening agent

80 Sodium alginate Stabilizing agent; suspending agent; tablet and capsule

disintegrant;

tablet binder; viscosity-increasing agent.

81 Silica gel Adsorbant

82 Sorbiton monooleate Solubilizer

83 Sodium stearyl fumarate Tablet and capsule lubricant.

84 Sodium chloride Tablet and capsule diluent; tonicity agent


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Sl. Excipient Use

85 Sodium metabisulfite Antioxidant.

86 Sodium citrate dihydrate Alkalizing agent; buffering agent; emulsifier; sequestering agent.

87 Sodium starch Binder

88 Sodium carboxy methyl

cellulose

Coating agent; tablet and capsule disintegrant;

tablet binder; stabilizing agent; suspending agent;

viscosity-increasing agent; water-absorbing agent.

89 Succinic acid Acidity

90 Sodium propionate Antimicrobial preservative

91 Titanium dioxide Coating agent; opacifier; pigment

92 Talc Anticaking agent; glidant; tablet and capsule diluent; tablet and

capsule lubricant.

93 Triacetin Humectant; plasticizer; solvent

94 Triethyl citrate Plasticizer

Glossary of Abbreviations ADI - Acceptable daily Intake

API - Active Pharmaceutical Ingredient

ARV - Anti-Retroviral

BA - Benzyl Alcohol

cGMP - Current Good Manufacturing Practice

CNS - Central Nervous System

d - Days

DF - Dosage Form

DPI - Dry Powder Inhaler

EMA - European Medicines Agency (was EMEA)

FDC - Fixed Dose Combination

GIT - Gastro-Intestinal Tract

HPMC - Hydroxypropyl Methylcellulose

IM - Intramuscular

IV - Intravenous

Na - Sodium

ODT - Oro-Dispersible Tablet

OTC - Over the Counter

ppm - Parts per million

PEG - Polyethylene Glycol

PG - Propylene Glycol

PVP - Polyvinyl Pyrrolidone

SC - Subcutaneous

SiO2 - Silicon Dioxide

y - Years

pharmaceutical excipients

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