Excipient

 An excipient is an inactive substance formulated

alongside the active ingredient of a medication, for the
purpose of bulking-up formulations that contain
potent active ingredients.
 Drug products contain both drug substance
(commonly referred to as active pharmaceutical
ingredient or API) and excipients. Formulation of API
with excipients is primarily to ensure an efficacious
drug product with desired properties and a robust
manufacturing process
 The resultant biological, chemical and physical properties
of the drug product are directly affected by the excipients
chosen, their concentration and interactions with the API:
 Consistency of drug release and bioavailability
 Stability including protection from degradation
 Ease of administration to the target patient
population(s) by the intended route
 Excipients determine the bulk of the final product in
dosage forms such as tablet, capsule, etc., the speed of
disintegration, rate of dissolution,release of drug,
protection against moisture, stability during storage,
and compatibility . Excipients should have no
bioactivity, no reaction with the drug substance, no
effect on the functions of other excipients, and no
support of microbiological growth in the product .
Ideal properties of excipient
 No interaction with drug
 Cost effective
 Pharmacologically inert
 Stable for handling
 Feasible
 Excipients are inactive ingredients used as carriers for
the active ingredients in a pharmaceutical product.
These may be classified into the following categories:
 Antiadherents
 Binders
 Coatings
 Disintegrants
 Fillers and Diluents
 Coloring Agents
 Glidants
 Lubricants
 Preservatives
 Sorbents
 Sweeteners
 DILUENTS
 Diluents increase the volume to a formulation to prepare tablets of the
desired size. Widely used fillers are lactose, dextrin, microcrystalline
cellulose, starch, pregelatinized starch, powdered sucrose, and calcium
phosphate.
 The diluent is selected based on various factors, such as the
experience of the manufacturer in the preparation of other
tablets, its cost, and compatibility with other formulation
ingredients. For example, in the preparation of tablets or
capsules of tetracycline antibiotics, a calcium salt should
not be used as a diluent since calcium interferes with
absorption of the antibiotics from the GI tract.
 Classification :
Diluents

Chemical nature Solubility

Organic materials Inorganic materials Insoluble Soluble

Dextrose Calcium phosphate

Calcium phosphate (II)
Dextrose Lactose (II)
Calcium phosphate (III)
Lactose Mannito Calcium phosphate
Calcium sulphate
Mannitol l (III)
Calcium carbonate
Sorbitol Sorbitol Calcium sulphate
Starch sucrose Calcium carbonate
sucrose Starch
 Purpose of diluents :
•to enhance bulkiness
•to provide improved cohesion
•to enhance flow
•to allow direct compression
manufacturing
Example-
 Calcium phosphate (10-15%)
 Starch (5-10%0
 Calcium sulphate (5-10%)
 Microcrystalline cellulose (5-15%)
 LACTOSE :
• most widely used diluent

• solubility – water soluble

Hydrous
used in wet granulation
Forms

Anhydrous shows fast disintegration, good friability,

practically no sticking, binding and
capping

hydrous form undergoes maillard reaction discoloration of certain drugs

( amine drug )

• Problem of browning due to contamination of 5-hydroxyfurfural which was

accelerated in the presence of basic amine drugs and catalyzed by tartarate, citrate
and acetate ions
 BINDERS
 Binders promote the adhesion of particles of the
formulation. Such adhesion enables preparation of
granules and maintains the integrity of the final
tablet. Commonly used binding agents include:
starch, gelatin and sugars ( sucrose, glucose,
dextrose, and lactose).
 Examples of Binders
Carboxymethylcellulose, sodium Karaya gum

Cellulose,microcrystalline(Avicel®) Starch, pregelatinized

Ethylcellulose Tragacanth gum

Hydroxypropyl methylcellulose Poly(acrylic acid)

Methylcellulose Polypvinylpyrrolidone
Acacia gum Gelatin
Agar Dextrin
Algin acid Glucose
Guar gum Molasses
 Binders

Cellulose
Starch
(1,4-beta-glycosidic linkages)
(1,4-alpha-glycosidic linkages)

Gellatin Polyethylene glycol (PEG)

Binders add mechanical strength to the

tablet or granules.
Disintegrants
 ( Added to a tablet formulation to facilitate its breaking or
disintegration when it contact in water in the GIT).

• Example: Starch- 5-20% of tablet weight.

• Starch derivative – Primogel and Explotab (1-8%)


• Clays- Veegum HV, bentonite 10% level in colored tablet only

• Cellulose

• Cellulose derivatives- Ac- Di-Sol (sodium carboxy methyl cellulose)

• Alginate

• PVP (Polyvinylpyrrolidone), cross-linked

 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.
Superdisintegrants
• Swells upto ten fold within 30 seconds when contact water.

• Example: Crosscarmellose- cross-linked cellulose, Crosspovidone- cross-

linked povidone (polymer), Sodium starch glycolate- cross-linked starch.

• These cross-linked products swell upto ten fold within 30 seconds when in
contact with water.

• A portion of disintegrant is added before granulation and a portion before

compression, which serve as glidants or lubricant. Evaluation of carbon
dioxide in effervescent tablets is also one way of disintegration
Lubricant and Glidants
 Lubricants are intended to prevent adhesion of the tablet
materials to the surface of dies and punches, reduce inter
particle friction and may improve the rate of flow of the tablet
granulation.

 Glidants are intended to promote flow of granules or powder material

by reducing the friction between the particles.
 Example: Lubricants- Stearic acid, Stearic acid salt - Stearic acid,
Magnesium stearate, Talc, PEG (Polyethylene glycols), Surfactants
 Glidants- Corn Starch – 5-10% conc., Talc-5% conc., Silica derivative -
Colloidal silicas such as Cab-O-Sil, Syloid, Aerosil in 0.25-3% conc.
 Compression lubricants prevent adherence of granule/powder to
punch die/faces and promote smooth ejection from the die after
compaction:
 Magnesium stearate is by far the most extensively used tableting
lubricant
 Lubricants tend to be hydrophobic, so their levels (typically 0.3 – 2%) need
to be optimised:
 Under-lubricated blends tend to flow poorly and show compression
sticking problems
 Over-lubricated blends can adversely affect tablet hardness and
dissolution rate
 Lubricants can also be used when compression isn’t involved,
e.g.
 In powder blends for filling into capsules to prevent adherence of
granule/powder to equipment surfaces and dosator mechanisms
 Coating the surface of multi-particulate dosage forms (including
intermediate product) to inhibit agglomeration of individual particles
Glidants
 Glidants promote flow of the tablet granulation or
powder materials by reducing friction between
particles.
 The commonly used glidants are talcum, starch,
colloidal silica, silicates, stearates, calcium phosphate
etc.
 The effect of glidants on the flow of the granules
depends on the shape and size of the particles of the
glidants and the granules
 As a general rule hydrophilic materials act better on
hydrophilic granules and lipophilic ones on the
lipophilic granules.
 The glidants in a particular formulation ensure
increasing flow of granules up to a certain optimum
concentration . If the concentration of the glidant is
taken beyond this, a drag action may come into
operation
 bringing down the rate of flow.
Most commonly; colloidal silicon dioxide (traditionally, talc was
used)
 Good bulk powder flowability is especially important during
high speed processing
 Glidants improve flow by adhering to particles and so reducing
inter-particulate friction
 Most common in dry powder formulations, e.g. direct compression tablets
 Can also be added to granules to improve flow prior to compression
 NB: can get undesirable “flooding” if flow is too good
 Very low levels required (ca. <0.2%)
 Control can be challenging with blends sensitive to levels
 Very low bulk density (0.03 – 0.04g/cm3)
 Difficult to work with (very voluminous) – not a standard excipient, only
added if needed
 Issues with dust exposure