2. Pharmaceutical Excipient
• Drug product contains mainly 2 substances : API &
excepients.
• The word Excepient is derived from the Latin 'excipere' which
means 'to except.'
• An excipient is a pharmacologically inert substance
,formulated alongside the active pharmaceutical ingredient
of a medication.
3. Properties of an ideal excipient
1. It should be colorless, odorless & tasteless
2. It should be non volatile, nontoxic & nonirritant.
3. It should be pharmacologically inert.
4. It should be compatible with the API in the preparation
5. It should have no interaction with the API.
6. It should be soluble in water as well as oil & fat
7. It should be effective in low conc. over a wide range of pH.
8. It should be stable itself & not affected by T, light & hydrolysis.
9. It should be cheap & readily available.
5. Role of excepients
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. Preventing aggregation or dissociation of API.
4. Enhance solubility & bioavailability of APIs.
5. Improved API stability in dosage forms including protection from
degradation/ denaturation.
6. Improved dosing compliance (to give a particular shape & to improve
palatability, elegance of the formulation).
7. Facilitate drug absorption & other pharmacokinetic considerations.
8. Maintaining the pH & osmolarity of the liquid formulations.
9. Modulating immunogenic responses of active ingredients
6. ☆ Diluents/fillers
▪ When the quantity of a drug for an individual dose is very small then it
is practically impossible to compres ; Then the inert substances which are
added to increase the bulk for easy compression a known as diluents.
Fillers typically increase the bulkiness of a tablet or capsule, making it
convenient for the consumer to use.
Usually the range of diluents may vary from 10-80% in dosage form
preparation.
▪ Types (based on chemical nature) :
1. Inorganic : Sucrose, lactose, glucose, sorbitol, mannitol,
Microcrystalline cellulose (MCC), Powdered cellulose, Dextrin,
Dextrose, Kaolin, Starch, Sucrose.
2. Organic : CaCO3, CaPO4, CaSO4.
7. Diluents/ Fillers
▪ Function of fillers:
1. Bulking agent: It enhances bulkiness by adding extra
volume & mass to a drug substance in the
preparation of dosage forms .
2. Compression aid: It improves cohesion state that
permits use of direct compress manufacturing. e.g.
MCC.
3. Powder flow: It enhances flow property. Good flow
of bulk powders is very important in designing a
robust commercial tablet product.
8. 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.
9. ☆ Binders:
• Binders are the substances which act as an adhesive to ‘bind
together’ powders, granules in tablets to result in the necessary
mechanical strength.
• Example : Sucrose, lactose, hydroxypropyl cellulose(HPC),
carboxymethyl cellulose(CMC), polyvenylpyrrolidone(PVP),
gelatin.
• Function of Binders include :
1. To promote cohesive compacts during direct compression.
2. To ensure the tablet remaining intact after compression.
3. To promote granulation & to ensure free flowing.
10. Binders
▪ Binders can be added to a powder in different ways :
1. As a dry powder with other extra cellular excipients in
dry granulation.
2. As a dry powder with other intra-granular excipients in
wet granulation.
3. Most commonly in wet granulation, the binder is added
already dissolved in the granulating fluid to enable a
more effective and controllable granule formation.
11. ▪ Classification :
Binders are classified according to their application:
1. 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. PVP, HPC, cellulose, &
polyethylene glycol.
2. Solution binders are dissolved in a solvent (for example
water or alcohol can be used in wet granulation
processes). e.g., PVP, HPMC, gelatin, startch, cellulose,
sucrose & polyethylene glycol.
3. Soluble in water/ethanol mix: PVP.
Binders
12. ☆ Disintegranting Agent
▪ Disintegrants are substances added to the drug
formulations, which facilitate dispersion or breakup of
tablets and contents of capsules into smaller particles for
quick dissolution when it comes in contact with water in
the GIT.
▪ 2 Types:
a. Substances which hydrate and swell up in contact with
water. e.g. potato starch, maize starch.
b. Substances which react with effervescent when they
come in contact with moisture. e.g. Na2CO3, citric
acid, tartaric acid.
14. 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
▪ Mode of action: The disintegration process occurs in 2 Steps :
1. First, water uptake occurs & the liquid wets the solid.
2. Secondly penetrates the pores of the tablet, by rupturing the
intra-particle cohesive forces that hold the tablet together.
Thereafter, the tablet breaks into smaller fragments. In
effervescent tablets, disintegrant functions by producing CO2 gas.
15. Disintegranting Agent
▪ Super disintegrates:
Super disintegrants are the substances, used at low conc.
which provides a rapid disintegration within 30 seconds
when they come in contact with water.
Significant improvement in disintegrant performance was
achieved with the introduction of the super disintegrant.
Example- Cross linked starch, cross linked cellulose, cross
linked PVP, cross linked alginic acid.
16. ☆ Lubricants & Glidants
▪ Glidants: Glidants are the substance which are used to promote
powder flow by reducing interparticle fiction & cohesion in the
pharmaceutical production of tablets and capsule.
▪ Functions : The role of the glidant is to improve the flowability
of the Powder. This is especially important during tablet
production at high production speeds & during direct compaction.
Glidants are used in combination with lubricants as they have no
ability to reduce die wall friction.
▪ Examples : Talc, silica, MgCO3, Mg stearate etc.
17. Lubricants & Glidants
▪ Lubricants: Lubricants are the substances which are used to
reduce friction between the walls of tablet & the walls of die
cavity in which tablet is formed.
Lubricants prevent ingredients from clumping together & from
sticking to the tablet punches or capsule filling machine.
▪ Types:
• 1. Hydrophilic- Generally poor lubricants, no glidant or anti-
adherent properties. e.g. Boric acid, Na lauryl sulphate, Mg
lauryl sulphate.
• 2. Hydrophobic- Hydrophobic lubricants are generally good
lubricants & are usually effective at relatively low
concentration. e.g. Talc, silica, waxes, stearic acid.
18. Lubricants & Glidants
▪ Function of Lubricants :
1. True lubricant rule : Reduce friction between the walls of
tablet & the walls of die cavity in which tablet is formed.
2. Anti-adherent rule : Prevent ingredients from sticking to
machine dosators, tamping pins etc.
3. Glidant rule : Enhance product flow by reducing
interparticulate friction.
19. Difference between lubricant and glidant
Glidant Lubricant
1. Used to promote powder flow by
reducing interparticle fiction &
cohesion
1. Used to reduce friction between
the walls of tablet & the walls of die
cavity in which tablet is formed.
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 glidants are solid 4. Lubricans may be liquid
5. e.g. Talc, silica, MgCO3, Mg stearate 5. e.g. Boric acid, Na lauryl sulphate,
stearic acid.
20. ☆ 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.
Example : BHT, BHT, alcohol, phenol, benzoic acid, Na
benzoate, boric acid, sorbic acid, parabens, K sorbate.
21. Preservatives
▪ Classification of preservatives :
A. On the basis of their action in bacteria
I. Bacteriostatic : inhibits the growth of bacteria.
II. Bactericidal : Kills bacteria.
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
22. Preservatives
VI. 85% concentrated sugar solution
IV. Aldehyde group
Formaldehyde
V. Mercurials group
Phenyl mercuric acetate
Phenyl mercuric nitrate
23. Preservatives
▪ Basic mechanism of action of preservatives :
1. Modification of membrane permeability
2. Denaturation of enzymes or other cellular proteins
3. Oxidation and reduction of cellular constituents
4. Hydrolysis
5. Interference with essential metabolites
24. ☆ Preservatives
▪ Why do we need to use preservatives in combination?
The use of two or more preservatives collectively known as combine
preservatives.
No single preservative processes all the ideal properties. Sometimes
a single preservative is not enough to kill or inhibit the growth of
microorganism. Therefore, it becomes necessary to use a
combination of preservatives to prevent the growth of
microorganisms. Such combinations give a broad spectrum of
antimicrobial qualities.
e.g. Combination of Alcohol, Parabens, Formaldehyde - able to kill a
wide range of microbes.
25. ☆ Antioxidant
▪ An antioxidant is a substance which is used to prevent the
oxidative degradation of the drug in the presence of oxygen or
peroxides.
They act by producing free radicals & these initiate chain
reactions that damage cells.
▪ Drugs that are sensitive to oxidation are:
Vit A,Ascorbic acid (Vit C), Vit D,Riboflavin (vit E), penicillin,
gentamycine, morphine, heparin, tetracycline etc.
26. Antioxidant
▪ Classification
1. On the basis of the source :
a. Natural antioxidant: These exist & available in nature. e.g.,
Vit E, vit C, carotenoids.
b. Synthetic antioxidant: These are isolated or synthesised by
an artificial mean. e.g. BHA, BHT, Tertiary butyl
hydroquinone.
2. On the basis of solubility :
1. Water Soluble: Citric Acid, Tartaric Acid, Ascorbic
Acid.
2. Oil Soluble: Catalase, peroxidase, carotenoids
27. Antioxidant
3. On the basis of function :
1. Primary antioxidant: Primary antioxidants act by breaking the
oxidant chain by interfering with the propagation step of
autoxidaton process.
e.g., BHA, BHT, vitE.
2. Synergist: They used in conjugation with a primary antioxidant.
They have the ability greatly to enhance antioxidant efficiency.
e.g., EDTA salt, citric acid, glycerine.
28. 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.
29. 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).
30. Antioxidants
▪ Uses of Antioxidants :
1. Used as food additives to protect against food deterioration.
2. Help in plant respiration, store plant materials in anaerobic
condition.
3. Used as stabilizer in fuels & lubricants to prevent oxidation.
4. In industries they are used to prevent oxidative degradation of
polymers, such as- rubber, plastics.
31. ☆ Sweetening agents
▪ Sweetening agents are employed in liquid formulations
designed for oral administration specifically to increase the
palatability of the therapeutic agent.
▪ Example : Sucrose, lactose, glucose, sorbitol, mannitol,
saccharin etc.
▪ Uses of sweetening agent:
1. The main sweetening agents employed in oral preparations are
sucrose, liquid glucose, sorbitol, saccharin & aspartame.
Aspartame is an artificial sweetening agent.
2. In antihelminthic & multivitamin tablets sweetening agents are
used.
32. Sweetening agents
Why mannitol is extensively used in chewable tablets ?
The use of different sweetening agents is primarily limited to chewable tablets
because except mannitol.
Sucrose - It may cause hyperglycemia.
Saccharine - Bitter after taste and has been reported to be carcinogenic.
Aspartame - lack of stability in the presence of moisture.
For the above reason, mannitol is used extensively in chewable tablet because
of :
1. It is about 72% as sweet as sucrose.
2. It does not produce hyperglycemia.
3. It does not have bitter after taste.
4. It has the stability in the presence of moisture.
33. ☆ Alkalizing agents
Alkalizing agents referred to the substances which are used to
managed disorder associated to low pH.
Alkalizing agents provide alkaline medium for product stability
in liquid preparations like suspension,emulsion,solution etc.
34. Alkalizing agents
▪ Examples :
A number of alkalizing agents are used to pharmaceutical
formulations. Some common Alkalizing agents are :
Sodium bicarbonate
Potassium bicarbonate
Potassium hydroxide
Ammonium carbonate
Calcium carbonate
Calcium acetate
35. Alkalizing agents
▪ Uses :
1. Alkalizing agents are used to treat acidosis due to renal
failure.
2. They are used to neutralize excess acid in the blood and
urine.
3. They are used for oral or parenteral therapy.
4. They prevent acid rising from stomach into esophagus.
5. Sodium bicarbonate as an Alkalizing agent when dissolves
in water or body fluids,forms NaOH that neutralizes gastric
acid.
36. Alkalizing agents
Alkalizing agents are used to balance the acids of our body and to
strengthen the effect of cleaning solutions. The administration of an
alkalinizing agent results in a lowering of plasma and extracellular
[H+], with a concurrent increase in [HCO3−].
So, Alkalizing agents also contribute to maintaining the pH level that
is vital to our health, keeping cholesterol, blood sugar, electrolytic
activity and the heart's circular system running smoothly.
Alkalizing agent excepients are important in pharmaceutical
formulations where the active pharmaceutical ingredient requires an
alkaline environment for stability or therapeutic effectiveness.
37. ☆ Acidifying agents
Acidifying agents are the substances which are used in liquid
preparation to provide alkaline medium for product stability.
Acidifying agents lower the pH of solution. They are also
known as Acidifiers. They are typically derived from phosphoric
acid or blends of phosphate ester anionic surfactants
containing free phosphoric acids.
38. Acidifying agents
▪ Examples :
Some mostly used acidifying agents are :
Acetic acid
Citric acid
Hydrochloric acid
Nitric acid
Fumaric acid
39. Acidifying agents
▪ Classification :
Acidifying agents are classified into 3 categories. These are :
1. Gastric acidifying agents : They are the drugs which are
used to control pH of stomach in patients suffering from
achlorhydria or hypochlorohydria.
2. Urinary acidifying agents : Used to render acidic urine to
enable treatment of some types of urinary disorders.
3. Systemic acidifying agents: Used to neutralize the alkaline
body fluids in patients suffering who are suffering from
systemic alkalosis.
40. Acidifying agents
▪ Uses :
1. To control pH in the stomach. They increase the level of
gastric acid in stomach when ingested and hence decrease
the pH of stomach.
2. To control pH in the urine.
3. To stable pharmaceutical product providing appropriate pH.
4. Used in pesticides production.
5. Citric acid is used to prepare effervescent tablets.
