Diluents

PHRM 210
 Diluents
• Also known as bulking agents or
fillers
• Added to the active ingredient in
sufficient quantity to make a
reasonably sized tablet
• A tablet should at least 50mg and
therefore very low dose drugs
(diazepam, clonidine hydrochloride)
will invariably require a diluent to
bring the overall tablet weight to at
 Diluents
• This agent may not be necessary if
dose of drug per tablet is high (e.g.
aspirin and certain antibiotics)
• Usually the range of diluents may
vary from 5-80%
 Diluents: Primary reason of
use
• Inert substance designed to make up
the required bulk of tablet when the
drug dosage itself is inadequate to
produce its bulk
 Diluents: Secondary reason
of use
To provide better tablet properties


such as:
• Improved cohesion (maintain proper
shape of tablet)
• To permit use of direct compression
manufacturing
• To promotes flow
• To adjust weight of tablet as per die
capacity
•
 Diluents
INSOLUBLE TABLET
 SOLUBLE TABLET


DILUENTS DILUENTS
• Starch • Lactose
• Powdered cellulose • Sucrose
• Microcrystalline • Mannitol
cellulose • Sorbitol
• Calcium
phosphates
 Diluents: Lactose
• Most widely used diluent in tablet
formulation
• Also used as a filler or diluent in
capsule formulation
• Several grades are available
S u ita b le fo r
 - Lactose (monohydrate) w et
 - Anhydrous lactose g ra n u la tio n
 - Spray dried lactose (better
mixing)
 Diluents: Lactose
• Has no reaction with most drugs
whether it is used in the hydrous or
anhydrous form
• Destroyed with amino compounds,
lactates, acetates and alkaline
lubricants
• Lactose on storage tends to lose
moisture
 Diluents: Spray dried
lactose
• Spray dried lactose blended with
microcrystalline cellulose
constitutes a good directly
compressible diluent
• It may also be used as a disintegrant
and a lubricant
• If lactose is to be used as a directly
compressible diluent it should
constitute roughly 50% of the
weight
 Diluent: Microcrystalline
cellulose
• Microcrystalline cellulose, often
referred to by the trade name
Avicel, is a direct compression
material.
• Microcrystalline cellulose is prepared
by hydrolysis of cellulose followed
by spray drying
• Two tablet grades of microcrystalline
cellulose exist: PH 101 (Powder) &
PH 102 (Granules)
 Diluent: Microcrystalline
cellulose
• It is extremely compressible and is
capable of yielding very hard
tablets which at the same time
disintegrate rapidly in water
• It is relatively expensive when used
as a diluent in high concentration
and thus used in combined with
other materials (lactose)
• 5 to 15% concentration of
microcrystalline cellulose is usually
 Diluents: Manitol
• Manitol is perhaps the most
expensive sugar used as a tablet
diluent
• Manitol is used in chewable tablet as
diluent because-
 - Negative heat of solution
 - Slow solubility
 - Pleasant feeling in mouth
• Relatively nonhygroscopic and can
be used in vitamin formulation, in
 Diluents: Modified Starch
• Used as a diluent, binder &
disintegrating agent: Sta-Rx 1500
and Celutab
• Free flowing
• Directly compressible
• Used in chewable tablet in place of
manitol because of their sweetness
and smooth feeling in mouth
• Contain 8 to 10% moisture & may
increase hardness after
 Diluents: Calcium
phosphates
• The dihydrate and anhydrous form of
dibasic calcium phosphate and
tribasic calcium phosphate are
used
• They are widely used both as wet
granulation and direct compression
diluents in tablet formulation
• Bulk density of calcium phosphates is
higher than that of organic fillers
 Diluents: Calcium
phosphates
• They are non hygroscopic. They are
used extensively in vitamin and
mineral preparations
• They are abrasive in nature and
hence can cause wear of tablet
tooling
• Sometimes their alkalinity is a major
source of drug instability
•
 Influence of diluents:
Bioavailability
• Although diluents are normally
thought of as inert ingredients,
they can significantly affect the
biopharmaceutical, chemical and
physical properties of tablet.
• The calcium salts interfering with the
absorption of tetracycline from the
gastrointestinal tract. They make
half the bioavailability of standard
product.
 Influence of diluents:
Bioavailability
• Antiepileptic drug sodium phenytoin
will form poorly absorbable
calcium-phenytoin complex, when
calcium sulphate dihydrate used as
diluent in the formulation. But using
of lactose as diluent improves
bioavailability of the antiepileptic
drug significantly.
 Influence of diluents:
Incompatibility
 Amine drugs + lactose (diluent)
 ↓ used with
 Metal stearate (Mg stearate)
 (Lubricant)
 ↓
 Discoloration of tablet with time