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RIPER PDIC
Bulletin, August
Some Important excipients used 2010 issue for

in tablet formulation download


Dear readers,

Diluents:
Get your copy of
RIPER PDIC Bulletin
Diluents are classified into 2 types.
here.

Organic Diluents (these are carbohydrates


Fibrodysplasia
or its derivatives) ossificans
progressiva

Dextrose (CERELOSE):Dextrose is in 2
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Dextrose (CERELOSE):Dextrose is in 2 Everything


forms Hydrous & anhydrous. Anhydrous
form is used when low moisture is desired you
byt the granules prepared from this type
are hard. Dextrose reacts with alkaline should
compounds and undergoes reaction with know
amines resulting in its discoloration to
brown color (Maillard Reaction) about
Lactose (Milk Sugar):Lactose is also a Fibrodysplasia
reducing sugar and undergoes Maillard
Reaction. This reaction occurs between ossificans
carbonyl group of reducing sugar (such as progressiva
lactose) and the amino group of drugs (like
aminophylline and amphetamine). This (FOP)
reaction is faster in alkaline environment Read About
as the amine group does not undergo
neutralization. This reaction gives poor Pharm.D./Ph.D in
odour. Chemically lactose is isomeric University of
containing a-lactose and v-lactose. At low Illinois - Chicago
College of
temperature of crystallization a-lactose is
Pharmacy-USA
formed and crystallization temperature of
93 deg C or above v-lactose is formed.
Hydrous Lactose (Pharmatose, Respitose) Manager / Sr.
Manager,
It is a-lactose monohydrate and is
Operations
generally used in wet granulation process.
Technical Suppport
Wetting of lactose leads to dissolution of - Product Support
lactose. The dissolved lactose forms a layer Technical Writing in
around the drug surface and retards the San Diego
dissolution of the drug. California United
States
Anhydrous Lactose:Compressibility and Summary of Duties
flow properties are poor. Hence it is and
affected upon long term storage. This is Responsibilities
also available in 2 forms: Anhydrous a- Hologic, Inc.
lactose & anhydrous v-lactose. Applied Geneticist
Disintegration time of anhydrous a-lactose Org Marketing
Statement All over
is very high. anhydrous v-lactose is a very
the world, Pfizer
fine crystalline in the form. It is less brittle,
colleagues are
has higher dissolution rate and greater
working together to
solubility. positively impact
health for

Commercially agglomerated lactose


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Commercially agglomerated lactose everyone,


(Anhydrous a-lactose in the granular form everywhere.

with enhanced binding properties) is Which dissolution


apparatus is used
available under the brand name
to evaluate
Tablettose. Spray Dried Lactose:It is a-
Transdermal
lactose in the crystalline form. It can be products ?
directly compressed after mixing it with what are the CYP
drug and other excipients such as probe studies are
disintegrant and lubricant. It has good useful in metabolic
compression and flow characteristics Fast - profiling of drug
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, PH-302), 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 non-super imposable mirror
images that rotate the plane of polarized

light in equal magnitudes but in opposite


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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 self-lubricating 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,
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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


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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


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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
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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%
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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
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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,
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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:


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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
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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

Excipients Brand Names:

MCC, Lactose Cellactose Sucrose,


Dextrin,Dipac Lctose, PVP,
Crospovidone,Ludipress Anhydrous
Lactose, Lactitol,Pharmatose,DCL 40 MCC,
Colloidal Silica,Proslov

Source:lachman
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Source:lachman
Topic:GPAT

About the Author

Author: Charan Karumuri


I am currently preparing for GPAT and would like to share GPAT
related information through my blogs.

GPAT Useful Links :

1. Top 5 GPAT Books


2. GPAT Resources
3. GPAT Practice Questions (Free )

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