Some Important excipients used in tablet formulation

Diluents:
Diluents are classified into 2 types.
Organic Diluents (these are carbohydrates or its derivatives)
Dextrose (CERELOSE):Dextrose is in 2 forms Hydrous & anhydrous. Anhydrous form is used when low
moisture is desired byt the granules prepared from this type are hard. Dextrose reacts with alkaline
compounds and undergoes reaction with amines resulting in its discoloration to brown color (Maillard
Reaction)
Lactose (Milk Sugar):Lactose is also a reducing sugar and undergoes Maillard Reaction. This reaction
occurs between carbonyl group of reducing sugar (such as lactose) and the amino group of drugs (like
aminophylline and amphetamine). This reaction is faster in alkaline environment as the amine group does
not undergo neutralization. This reaction gives poor odour. Chemically lactose is isomeric containing alactose and v-lactose. At low temperature of crystallization a-lactose is formed and crystallization
temperature of 93 deg C or above v-lactose is formed. Hydrous Lactose (Pharmatose, Respitose) It is alactose monohydrate and is generally used in wet granulation process. Wetting of lactose leads to dissolution
of lactose. The dissolved lactose forms a layer around the drug surface and retards the dissolution of the
drug.
Anhydrous Lactose:Compressibility and flow properties are poor. Hence it is affected upon long term
storage. This is also available in 2 forms: Anhydrous a-lactose & anhydrous v-lactose. Disintegration time of
anhydrous a-lactose is very high. anhydrous v-lactose is a very fine crystalline in the form. It is less brittle,
has higher dissolution rate and greater solubility.
Commercially agglomerated lactose (Anhydrous a-lactose in the granular form with enhanced binding
properties) is available under the brand name Tablettose. Spray Dried Lactose:It is a-lactose in the
crystalline form. It can be directly compressed after mixing it with drug and other excipients such as
disintegrant and lubricant. It has good compression and flow characteristics Fast - Flo Lactose (NF Hydrous)
It is hydrous lactose in the form of spherical crystals or amorphous agglomerates. Spherical crystals are easy
to compress compared to agglomerate lactose.
Mannitol:It is inert, non-hygroscopic diluent and used mostly in vitamin formulations that are moisture
sensitive. Formulations containing mannitol requires more amount of lubricants as they have less
flowability. Mannitol gives softer granules compared to sucrose and dextrose Microcrystalline Cellulose:It is
used as a diluent, disintegrating agent and lubricating agent. When concentration of the active ingredient
exceeds 20% then the lubricating power of MCC is lost. Commercially
MCC is available under the brand names Avicel PH (GRADES OF PH 101, PH-102, PH-105, PH-301, PH302), Emcocel and Vivacel. Avicel PH-101 is powdered while PH-102 is granular. Avicel PH-301 & PH-302
contain denser particles and has enhanced flowability, decreased lubricity and compressibility Sorbitol
(Neosorb 60, Sorbogen & Sorbidex P) Sorbitol and Mannitol are optical isomers (enantiomers that are nonsuper imposable mirror images that rotate the plane of polarized light in equal magnitudes but in opposite
directions).

Sorbitol when is used in combination with mannitol reduces the cost of diluents. Sorbitol and Mannitol have
low calorific value. They are non-carcinogenic. Starch Starch USP Grade has poor compression and
flowability characteristics. It contains 11 - 14 % moisture. Modified forms of starch are available like Sta-Rx
1500, Emdex, Celutab, National 1551 (partially hydrolyzed or pregelatinized starch) Sta-Rx 1500 It is a selflubricating agent but if the drug content is between 5 - 10% then addition of other lubricating agents is
needed. It gets softened when it is combined with large amounts of magnesium stearate ie greater than 0.5 %
Emdex and Cellutab These are free flowing and directly compressible hydrolyzed starches. The composition
of these hydrolyzed starches is 90 - 92 % dextrose, 3 - 5 % maltose & 8-10 % of moisture. The tablets
produced are hard in nature.
Sucrose It is available in different particle sizes like granular (table sugar), fine granular, fine, superfine and
confectioners sugar (very fine sugar in which 80% should pass through #325 mesh. Confectioner sugar with
3% cornstarch is used for wet granulation process to avoid caking of tablets. Tablets containing Sucrose has
long disintegration times. Sucrose granules when used in the form of dry powder, then either water or
hydroalcoholic binder is added.
Commercial Brands are DiPac, NuTab & Sugartab Inorganic Diluents (Salts of metals of calcium and
magnesium and exhibit properties like abrasiveness, absorbency, lubricity, mechanical strength, pH and
solubility)
Dibasic Calcium Phosphate (DCP); DiTab, Fujicalin, Emcompress It is stable both physically and
chemically and relatively inexpensive. The dehydrate form has a pH of 7.0 - 7.3 and must be used with
drugs that are stable in alkaline environment. DCP loses water of hydration from their outer surface under
low humidity and high temperature. This diluent is non-hygroscopic. When DCP is used along with other
hygroscopic diluents such as microcrystalline cellulose, the moisture loss from DCP to MCC occurs to the
extent where the tablet softens. This softening due to weakening of intraparticular bonds of the diluents
increases the degradation of drugs which are moisture sensitive eg: Vit A. Flowability is good but
compressibility is poor. When DCP is used, lubricant is not necessary. Binders like Starch Paste, PVP, MC
etc are stable with DCP. Inorganic acetates develop acetic odour upon long time storage. Absorption profile
of many drugs (eg: Tetracycline) is affected due to calcium salt Tribasic Calcium Phosphate; Tritab It is very
rarely used in wet granulation process. It is non-hygroscopic.
Calcium Suphate Dihydrate; Delaflo Non-hygroscopic powder with mild abrasive properties. It is used
with acidic, neutral & basic drugs. It is low cost and used with polymeric binders like PVP, MC, Starch paste
etc. Calcium Carbonate:It is non-hygroscopic, physically and chemically inert and inexpensive. It is a
directly compressible diluent. It also has antacid effects and also as a nutritional supplement. Disadvantage:
It encounters same problems as MCC when over wetted or mixed, it leads to formation of hard granules that
disintegrate slowly. This problem is overcome when used with starch, MCC etc

BINDERS They are also called as pharmaceutical glue.

Binders are of 2 types:
1. Dry binders - added in the form of powder to the powder blend of tablet. The tablet mixture (containing
binder) is wetted with a suitable liquid like water or hydroalcoholic solution.
2. Wet binders - these are added in the form of solution.

The solution is prepared by dissolving the binder in an appropriate solvent like water or hydroalcoholic
solution. The binder is then added to the powder tablet blend by 4 ways ie Low Shear, High Shear,
atomization and Extrusion. Sugars are also used as binding agents. Eg: Sucrose. Sucrose as a binder can be
used in the range of 20 - 85 %. The more the amount of binder, harder the granules and hence harder the
tablet. If sucrose is prepared in hydroalcoholic solutions, comparatively softer granules can be obtained. The
sugar solution must be of high concentration to avoid bacterial multiplication. In iron tablets containing
ferrous sulphate, sucrose plays a dual role as a binder and also prevents the oxidation of ferrous sulphate.
Based on the source, Binders are of 2 types: 1. natural polymeric binders 2. synthetic polymeric binders

Natural Polymeric Binders Compound Notes

Advantage / Disadvantage Gelatin A: 2 - 10% solution is a strong binder compared to starch paste.
Synthetic polymeric binders like MC, PVP are more used instead of gelatin.
Gelatin is hydrated by soaking in cold water for hours or by keeping it overnight. The soaked gelatin is
heated to boil, so as to form gelatin solution. This hot gelatin solution must be used as early as possible to
prevent gelling upon cooling Tablets of gelatin are hard to disintegrate. It acts as a media for the growth of
bacteria and molds. Hence preservatives are added.
Gum Acacia It is a binder at 5 - 10 % concentrations. For drugs like Mephenesin where granulation is
difficult, Acacia is a suitable binder. Granules are hard Acacia is a natural product which is prone to high
bacterial contamination
Gum Tragacanth It is binder at 5 - 10 % Concentrations. Compared to acacia the granules are not hard It is a
natural product prone to bacterial contamination
Starch Various forms of starch which can be used are Starch 1500, Starch paste and pregelatinized starch.
Pregelatinized startch is obtained by cooking the starch and drying it subsequently. It can be added in the dry
form to the powder blend of the tablet followed by wetting with water. It causes overwetting and thickening
of the granules. It can be used instead of starch paste. It is soluble in water but starch is insoluble.
Synthetic Polymeric binders Ethylcellulose It is insoluble in water but soluble in alcohol. 2 - 10% low
viscosity grade is used as a binder. It is a non aqueous binder, hence suitable for drugs that are sensitive to
the presence of water.
Powders with poor compression characterstics (ie drugs like Paracetamol, Caffeine, Meprobamate & Ferrous
fumarate( can be granulated using Ethylcellulose)
Methylcellulose It is used in aqs concentration at 1 - 5 % solution. Binding strength depends on the viscosity
grade. It is available in low (10 - 50 cps) and high viscosity (1000 - 10000 cps) grades. Comparatively good
binder than lactose, mannitol etc PEG 6000 Its Melting point is 70 - 75oC and solidifies at 56 - 63 oC. It is
used for drugs that are sensitive to alcohol and water. It acts as a anhydrous granulating agent
PVA They are water soluble film forming agents which are used as binders. It produces soft granules
(compared to acacia) and undergo easy disintegration and usually do not harden upon long term storage. Thy
are not contaminated with bacteria PVP It is slightly hygroscopic and expensive. Granules of insoluble

powders are prepared by dissolving PVP in aqueous or hydroalcoholic solutions. It is used to prepare
effervescent tablets and chewable tablets. In chewable tablets, it can be used as a binder. Addition of 2 - 3%
glycerine to these tablets decreases tablet hardening upon long time storage.
Sod CMC Used in concentrations of 5 - 15% to produce soft granules for both soluble and insoluble
powders. Tablets harden upon storage and prolong disintegration time Incompatibility between Sod CMC
and Aluminium, Calcium & Magnesium salts have been observed.

Adsorbing agents or Adsorbents: Some amounts of semisolid or liquid excipient may have to be added in
some formulation. The added adsorbent adsorbs the semisolid or liquid excipients and avoids cohesiveness
of tablet powder to allow proper tablet compression. Adsorbents usually decrease the hardness of the tablet.
Silicon Dioxide is used as a adsorbent. During the tabletting of volatile drugs (eg: Nitroglycerine),
evaporation of the drug results in loss of therapeutic activity. This can be overcome by adding adsorbents
like PEG 400 or PEG 4000 at concentrations of 8.5%. Cross linked Povidone is also used to improve the
stability of in tablet formulation.
Fullers Earth: Widely used as an adsorbent in tablet formulation Kaolin: it is purified aluminium silicate and
is used as an adsorbent. Disintegrating agents: Disintegrants cause disruption of cohesive forces existing
between the granules thereby causing the breakdown of the tablet.

Addition of Disintegrating agents is done by 2 methods:

1. Internal addition - here the agent is added to the tablet powder blend along with other ingredients. This
mixture is granulated and the granules so produced are compressed to form tablets.
2. External addition - powder tablet mixture, granulating liquid is added to form granules. The disintegrating
agent is added to the granules and then compressed to form tablets. This is the most widely used method.
Mechanism of disintegration:
1. Improved capillary forces for rapid uptake of water or GI fluids
2. Swelling of the disintegrant when in contact with water or GI fluids
3. Release of Gas to disintegrate the tablet - In this method the disadvantage is to control the environment
conditions. Elevated humidity the disintegrant absorbs moisture and disintegrating effect is lost
4. enzymatic degradation of binders - non-cohesive tablets are disintegrated by adding little quantity of
suitable enzyme. This is done by adding binders by wet granulation process hence making the tablets of
cohesive nature and then adding enzymes.
Disintegrating agents Information
Alginic Acid Polymer obtained from the seaweed consisting of D-mannuronic and L-glucuronic acid units.
Used at 5 - 10% w/w concentration. Used for granulation of acidic and neutral substances only. Alginates
have gelling property and hence can prolong the disintegration time of tablets.

MCC Most effective at 5 - 15% Concentrations. Disadvantages: Development of static charges on the MCC
particle occur in presence of moisture leading to separation of MCC particles, leading to non-uniform
disintegration. Addition of binders in tablets by wet granulation does not disintegrate the tablet readily. It
cannot be used with moisture-sensitive drugs .
Guar Gum Natural gum. In alkaline tablets, discoloration occurs with ageing. It is unaffected by pH,
moisture content and tablet matrix solubility. It is an excellent disintegrant at 2 - 8 % w/w
Sodium Starch Glycolate Used at 2 - 8 % w/w. Semi synthetic agent. Rapid and Uniform disintegration is
achieved
Starch Corn starch USP is used at concentration of 5 - 15 %. Used as a disintegrant in wet granulation
process. HPMC, MC & Sod CMC They are used at Concentrations of 5 - 10% w/w. they are used in
conjunction with starch and MCC to get good disintegration action on tablets Super Disintegrants Modified
Starch SSG (NF) - Explotab, Tablo Modified Cellulose Croscarmellose (NF) - Primellose, Solutab Cross
Linked PVP Crospovidone PolyclarAT

Anti-Frictional Agents - Lubricating agents:

These reduce the friction between the granules and the die wall of tablet press. Lubricants exert their action
by 2 mechanisms:
1. Hydrodynamic or fluid lubrication eg: Mineral oil (Liquid Paraffin)
2. Boundary Lubrication Eg: Magnesium Stearate
Lubricating agents are of 2 types:
1. Water Soluble lubricants eg: Sod Lauryl Sulfate, PEG 4000 & PEG 6000
2. Water Insoluble lubricants eg: Calcium or Magnesium Stearate, Mineral Oil With Mineral Oil - Mottling
of tablet occurs and is more pronounced in colored tablets especially dark colored tablets. This is due to the
formation of oil spots on the surface of the tablets.
The granules which are sprayed with mineral oil must be compressed in 1 - 2 days otherwise the oil can
penetrate the granules thereby losing its lubricating efficiency. Talc - Pharma grade talc it must be free of
asbestos. Talc delays the disintegration time of the tablets. Stearic Acid - it is insoluble in waer and not an
effective lubricant compared to Magnesium Stearate. It possesses incompatibility problems with alkaline
substances such as sod. Saccharine and Phenobarbital Sodium
Anti-frictional agents - Glidants:
These are added to improve the flow properties of the granules. Eg: Cab-O-Sil, Corn Starch
Wetting Agents:

These agents are added to formulations containing poorly soluble components. This is done to enhance the
dissolution rate.
Types of wetting agents are:
1. Hydrophilic Colloids - Alginates, Bentonite, Cellulose Derivatives, Tragacanth
2. Surfactants - SLS, Polysorbates, Sorbitan Esters etc

Organoleptic Agents:
1. Coloring agents * Artificial agents - these are used and added as per specifications in the FD & C act. *
Natural Coloring agents * Dyes - soluble coloring agents * Lakes - dyes in the form of dry powders
absorbed on hydrous oxide as aluminium hydroxide. * Pigments - insoluble coloring agents available as
powders
2. Flavoring agents - these are added just before compression inorder to prevent volatilization (as they are
volatile oils). Water soluble flavoring agents have poor stability.
3. Sweetening agents - these are added to impart taste to the tablet formulation. Eg: Saccharin - 1100 times
more sweeter than sucrose. It has a bitter after taste. This bitter after taste can be reduced by adding small
qty of sodium chloride.
4. Co-processed Excipients - these are a mixture (pre-blend) of one or more excipients which are commonly
used in conjunction with each other to improve their characteristics. They possesses better tabletting
properties. Co-Processed