An excipient is a pharmacologically inactive/ inert substance formulated alongside the active pharmaceutical ingredient of a medication. Drug products contain both drug substance (commonly referred to as active pharmaceutical ingredient or API) and excipients.

1. Pharmaceutical Excipient
Shohan Hossain
B. Pharmacy, JUST
01736400361

2. Pharmaceutical Excipient
• An excipient is a pharmacologically inactive/ inert
substance formulated alongside the active
pharmaceutical ingredient of a medication.
• Drug products contain both drug substance
(commonly referred to as active pharmaceutical
ingredient or API) and excipients.

3. • 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.

4. 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

5. Classification of excipients
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.
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.

6. 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 colorless, odorless 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.

7. • 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
• E.g: Lactose: Diluent, Carrier
Diffrenet grade
• Wet Granulation: finer grades
• Direct Compression: spray dried lactose
• For dry powder inhalers: crash-crystallization fine-
milled lactose with a coarser fraction for flow and a
finer fraction to enhance API aerosolization and
delivery to the lungs.

8. 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.
 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

9. Diluents/ Fillers
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.
Powder flow: Good flow of bulk powders is very
important in designing a robust commercial tablet
product.

10. 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 in all acceptable grade.
8. They do not alter bioavailability of the drug.
9. They must be color compatible.

11. Diluents/ Fillers
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

12. 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 in tablets to result
in the necessary mechanical strength
Typical features of binders: A binder should be
compatible with other products of formulation and add
sufficient cohesion to the powders.

13. Binders:
• 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.

14. 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., Pre-gelatinized 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

15. Disintegranting Agent
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.
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
Na2CO3, citric acid and tartaric acid.

16. Disintegranting Agent
• Ideal properties of disintegrate:
• 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.

17. Disintegranting Agent
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, Alginate.
During manufacturing the tablets disintegrating agents are
added in two steps-
a. Major par is incorporated to the powder before
granulation.
b. b. Other part is mixed with the dried granulation along
with lubricants before compression.

18. Disintegranting Agent
The disintegrating time depend on-
1. Quality of diluent, binder, lubricant
2. Hardness of tablet
3. Size of granules
4. And finally on coating.

19. Disintegranting Agent
Super disintegrates:
These disintegrates which swells up to 10 to fold within
30 seconds when they come in contact with water.
Significant improvement in disintegrant performance was
achieved with the introduction of the super disintegrant.
For example- Cross carmellose, cross linked cellulose,
Cross providone, Sodium starch glycolate,cross linked
starch.
Evaluation of CO2 on effervescent tablet is one of the
ways of disintegration.

20. Lubricants & Glidants
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 concentration.

21. Lubricants & Glidants
Examples of Lubricant:
Polyethylene glycol, Stearic acid, Magnesium
stearate, Calcium stearate, Glyceryl monostearate,
Isopropyl Myristate, Polyvinyl Alcohol, Sodium
Stearyl Fumarate

22. Lubricants & Glidants
• Glidants: A substance 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 : 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 : Fumed silica, Colloidal silicon dioxide, talc,
syloid, aerosil and magnesium carbonate.

23. Difference between lubricant and glidant
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. Usually glidant are solid 4. Lubricant may be liquid
5. e.g. Silica, Magnesium carbonate,
talc, syloid, aerosil etc
5. e.g. Stearic acid, Magnesium
stearate, Calcium stearate,
polyethylene glycol etc.

24. 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.
preservatives Action:
bacteriostatic preservatives.
bactericidal preservatives.

25. Preservatives
Desired Properties of ideal preservative:
1. Exert a wide spectrum of antimicrobial activity at low inclusion
levels.
2. It should be effective against a wide range of microorganisms such
as bacteria, mold and fungi etc at room temperature.
3. It should be stable and effective over a wide range of pH.
4. It should be effective at low concentration.
5. Maintain activity throughout product manufacture, shelf life and
usage.
6. Not compromise the quality or performance of product, packaging
or delivery system.
7. Not adversely affect patient safety or tolerance of the product.

26. Preservatives
8. It should be chemically compatible with other ingredients of the
formulation.
9. It should be soluble in aqueous phase when used in emulsions.
10. If the system is biphasic, the partition-coefficient should be in
favor of the aqueous phase.
11. It should be nontoxic, nonirritant.
12. It should be odorless, tasteless, and should not impart color in
the formulation.
13. It should be neutral and should not react chemically with other
constituent.
14. It should be of low volatility to ensure that loss does not occur
during storage.

27. Preservatives
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.

28. Preservatives
Why do we need to use preservatives in
combination?
Alcohol, Parabens, Formaldehyde donors- able to
kill a wide range of microbes.
Sodium Benzoate or Potassium Sorbate are only
effective against yeasts and molds but have a lower
activity against bacteria.
several studies have cautioned that parabens have
estrogenic or endocrine-disrupting properties.

29. Preservatives
Types of dosage form
Preservative required Not required
Liquid dosage form
Solid dosage form Tablet,
capsule)
Injectables
Very hypertonic liquid
dosage form
Topical One time use Injectables
Semisolid
100% non aqueous liquid
dosage form

30. Preservatives
Dosage
form
Name of Preservatives Concentration(%)
Oral
Benzoic acid 0.1
Sodium benzoate 0.1-0.2
Methyl Paraben and salts 0.1
Propyl Paraben and salts 0.05
Butyl Paraben and salts 0.02
Alcohol 15-20
Glycerin 45
Sorbic acid and salts 0.1
Propionic acid and salts
Dehydroacetic acid

31. Preservatives
Dosage form Name of Preservatives Concentration(%)
Injectables
and
ophthalmic
Benzalkonium chloride 0.01
Benzothonium chloride 0.01
Benzyl alcohol 2
Chlorobutanol 0.5
Phenyl ethyl alcohol 0.5
Cresol 0.3-0.5
Chlorocresol 0.1-0.2
Methyl paraben 0.1
Propyl paraben 0.02
Phenol 0.5
Phenyl mercuric nitrate 0.002

32. Preservatives
Dosage form Name of Preservatives
Topical
Benzoic acid
Phenol
Sorbic acid
Alcohols (ethyl and Propyl)
Quaternary ammonium salts
Mercurals

33. Preservatives
A. On the basis of their action in bacteria
I. Bacteriostatic
II. Bactericidal
B. On the basis of their chemical structure
II. Ester group
Methyl paraben
Ethyl paraben
Propyl paraben
III. Phenol group
Phenol
Cresol
Chlorocresol
Benzyl alcohol
I. Acid group
Benzoic acid
Sorbic acid
Propionic acid

34. Preservatives
VII.85% concentrated sugar solution
IV. Aldehyde group
Formaldehyde
V. Mercurials group
Phenyl mercuric acetate
Phenyl mercuric nitrate
VI. Quaternary ammonium compound
Cetyl trimethyl ammonium bromide
Benzalkonium chloride

35. Preservatives
I. Modification of membrane permeability
II. Denaturation of enzymes or other cellular proteins
III. Oxidation and reduction of cellular constituents
IV. Hydrolysis
I. Interference with essential metabolites
Basic mechanism of action of preservatives

36. 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.
1. On the basis of the function antioxidants are 2 types:
a. Primary antioxidant/ true antioxidant.
b. Synergist.

37. Antioxidant
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)
b. Synergist: The synergist class of antioxidants has little inherent
antioxidant 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
2. Oil Soluble: Ascorbyl Palmitate, Mono-isopropyl Citrate,
Palmityl Phosphate, Mono-stearyl Citrate

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

39. Antioxidant
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.

40. Antioxidant
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).

41. Antioxidant
Drugs that are sensitive to
oxidation are:
1. Ascorbic acid (Vitamin C)
2. Chlorpromazine.
3. Cyanocobalamine 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

42. Sweetening agents
Sweetening agents are employed in liquid
formulations designed for oral administration
specifically to increase the palatability of the
therapeutic agent.
Uses of sweetening agent:  The main sweetening
agents employed in oral preparations are sucrose,
liquid glucose, glycerol, sorbitol, saccharin, sodium
saccharide and aspartame. Aspartame is an artificial
sweetening agent.

43. Sweetening agents
mannitol is extensively used in chewable tablets:
Sugar - hyperglycemia.
Saccharine - bitter after taste and has been reported to be
carcinogenic.
Aspartame - lack of stability in the presence of moisture.
Mannitol –
1. Is reportedly about 72% as sweet as sucrose.
2. It does not have bitter after taste.
3. It has the stability in the presence of moisture.
4. It does not produce hyperglycemia.