2. 2
CONTENTS
Introduction to diluents
Classification
Advantages and disadvantages
Introduction to disintegrants
Classification
Advantages and disadvantages
Conclusion
References
3. INTRODUCTION TO DILUENTS
In addition to the active or therapeutic ingredients, tablets contain a number of inert materials.
The latter are known as additives or excipients. They may be classified according to the part
they play in the dosage form.They are binders, diluents, disintegrants, lubricants, sorbents,
coating agents, preservatives, colours, flavours and sweetners.
DILUENTS
Diluents are the fillers used to increased the bulk content in the dosage form this is done in a
situation where the active constituent to be incorporated in the formulation is of less quantity.
PURPOSE OF SELECTION
To enhance bulkiness
To provide improved cohesion
To enhance flow
To allow direct compression manufacturing
3
4. IDEAL PROPERTIES OF DILUENTS
• They must be non toxic
• They must be commercially available in acceptable grade
• There cost must be low
• They must be physiologically inert
• They must be physically & chemically stable
• They must be free from all microbial contamination
• They do not alter the bioavailability of drug
• They must be color compatible.
CLASSIFICATION
Diluents are classified into 3 types.
• Based on natural source
• Based on chemical nature
• Based on solubility
4
5. CLASSIFICATION OF DILUENTS
A) BASED ON SOURCE
1)SUGARS
Dextrose, Lactose, Sorbitol, Mannitol.
Sucrose.
2)POLYSACHCHARIDES
Starch, Micro crystalline cellulose,
Modified-starch.
B) BASED ON CHEMICAL NATURE
1)ORGANIC MATERIALS
Dextrose, lactose, mannitol, sorbitol, starch,
sucrose.
2)INORGANIC MATERIALS
Dibasic calcium phosphate,
Tribasic calcium phosphate,
Calcium carbonate,
C) BASED ON SOLUBILITY
1)SOLUBLE DILUENTS
Dextrose, lactose,
Mannitol, Sorbitol, Sucrose.
2)INSOLUBLE DILUENTS
Starch, Dibasic calcium phosphate,
Tribasic calcium phosphate,
Calcium carbonate,
5
6. STARCH
Starch may be obtained from corn, wheat or potatoes. It is occasionally used as a tablet
diluent
· USP grade of starch is usually possesses poor compression and flowability moisture
content between 11 to 14%.
· Specially dried types of starch that have a standard moisture level of 2-4% are
available, but are costly.
DIRECTLY COMPRESSIBLE STARCHES
Sta–Rx 1500 – free flowing, directly compressible starch
– if drug content lies between 5-10%, it require other lubricating agent.
Emdex and cellutab - due to sweet taste and cool feeling ,used in place of mannitol.
DEXTROSE (D–Glucose)
Available in two forms: as hydrates and anhydrous forms.
Dextrose turns brown in the presence of alkaline compounds and undergo reaction with
amines, lactose and sucrose resulting in its discoloration.
Available under brand name- CERELOSE 6
7. LACTOSE (MILK SUGAR)
Lactose is the most widely used diluent for tablet formulation.
It is obtained in hydrous and anhydrous form. The anhydrous form, picks up
moisture when exposed to elevated humidity. Such tablets should be packed in
moisture proof packets or containers. When a wet granulation method is employed,
the hydrous form of lactose should generally be used.
3 grades of lactose are commercially available:
i. 60 to 80 mesh – coarse
ii. 80 to 100 mesh – regular grade
iii. 200 to 450 mesh -- impalpable
Lactose is a reducing sugar and undergoes Maillard reaction.
Available in different forms : hydrous lactose, unhydrous lactose, spray dried
lactose and fast flo lactose.
Brand names : PHARMATOSE, RESPITOSE, TABBLETOSE.
7
8. MANNITOL
It is an odourless, white, crystalline powder with slight sweet taste. It dissolves slowly
and imparts a cool sensation in the mouth due to its negative heat of solution, hence used
in chewable tablet diluent.
Mannitol being inert and non – hygroscopic is used in vitamin formulations which are
moisture sensitive.
Formulations containing mannitol require large amount of lubricants due to its less
flowability.
Available under brand name : MANNOGEN 2080.
SORBITOL
It is white, granular powder which is water soluble. Sorbitol and mannitol are optical
isomers. Sorbitol when used in combination with mannitol reduces the cost of diluent.
Available brand names : NEOSORB 6O, SORBOGEN AND SORBIDEX P.
8
9. SUCROSE
It is a white odourless, sweet tasting substance available in different particle sizes like
granular, fine granular, fine, super fine and confectioners sugar. Confectioner sugar
with 3% corn starch is used for wet granulation to avoid caking of tablets.
Sucrose is hygroscopic, soluble in water and alcohol , it has good compactibility and
stability. Tablets containing sucrose possess long disintegration time.
Brand names of sucrose based diluents
BRAND NAMES COMPOSITION
DiPac
Nu Tab
Sugartab
97% sucrose + 3%
Modified dextrin.
95% sucrose + 4%
invert sugar + small
quantities of corn and
magnesium stearate.
90 – 93% sucrose + 7 –
10% invert sugar.
9
10. MICROCRYSTALLINE CELLULOSE ( MCC )
It is white odourless, tasteless inert crystalline powder with good flowability and contains
porous microfibres of cellulose. As length of cellulose polymer increases, the tensile strength
of the tablet also increases.
It is used in both direct compression and wet granulation methods of tabletting.
When used in wet granulation MCC promotes faster and uniform distribution of granulating
agent.
Available brand names : AVICEL PH, VIVACEL.
DIBASIC CALCIUM PHOSPHATE
It consist of small micro crystals of (dibasic) calcium phosphate in the form of free flowing
aggregates. It is a fine white powder, insoluble in water.
Directly compressible dibasic calcium phosphate occurs in dihydrate form, and loses its water
of hydration at temperature above 60 degree Celsius. It does not require lubricants.
Available brand names : DITAB
10
11. TRIBASIC CALCIUM PHOSPHATE
It has properties similar to dibasic calcium phosphate. It is a fine, white powder,
insoluble in water, slightly alkaline in nature and non – hygroscopic. It is less used in
wet granulation.
It should not be used with :
Salts of strong acids,
Acetate salts,
Palmitate or acetate esters of vitamin E or vitamin A.
Available brand names : TRITAB
CALCIUM CARBONATE
It is dense, fine white powder which is usually insoluble whose solubility depends on
pH.
It is obtained from grounded oyster shells and mined limestone.
It is directly compressible diluent which exert significant pharmacological action as an
antacid and also as nutritional supplement.
11
12. 12
ADVANTAGES
Provide mechanical strength to the tablet.
Non – toxicity.
Enhance compression and bulkiness.
Good organoleptic properties.
DISADVANTAGES
• Some large amount of diluents causes hardness of tablet.
• Forms caking of tablet.
• It should not be used with salts of strong acids and acetate salts .
13. INTRODUCTION TO DISINTEGRENTS
DISINTEGRANTS
Disintegrants induce breakup of dosage form when it comes in contact with
aqueous fluid in the GIT and this process of desegregation of constituent particles
occurs, before the drug dissolution is known as disintegration process and
excipients which induce this process are known as disintegrants.
PURPOSE OF SELECTION
The objectives behind addition of disintegrants are to increase surface area of the
tablet fragments and to overcome cohesive forces that keep particles together in a
tablet.
IDEAL PROPERTIES
The ideal properties of disintegrants include, good hydration, poor solubility and
poor gel formation capacity.
13
14. CLASSIFICATION OF DISINTEGRANTS
A) STARCH AND CELLUSE BASED EXCIPIENT
Starch, Pregelatinisied starch, Microcrystalline cellulose,
B) SOME CLAYS
Veegum HV, Bentonite.
C) SOME GUMS
Agar, Guar gum,
Tragacanth, Alginates.
D) SOME RESINS
Polacrilin potassium
E) FINELY DIVIDED SOLIDS
Colloidal silicon dioxide,
Magnesium aluminum silicate.
14
15. STARCH
Starch was the first disintegrating agent widely used in tablet manufacturing, among which
potato, maize and corn starches are the most common types used.
The typical concentration range of starch is 5-20% of tablet weight. Cost is very low.
PREGELATINISED STARCH (STA-1500)
Pregelatinized starch is widely used and produced by the hydrolyzing and rupturing of the
starch grain. It is a directly compressible disintegrants and its optimum concentration is 10%.
The main mechanism of action of Pregelatinized starch is through swelling.
MICROCRYSTALLINE CELLULOSE (AVICEL)
Like pregelatinized starch, microcrystalline cellulose is widely used in formulations because
of its excellent flow and binding properties.
• It is also an effective tablet disintegrant when used in a concentration of between 10-20%.
15
16. ALGINATES
Alginates are alginic acid and salts of alginic acid. Alginic acid is insoluble in water, slightly
acidic in reaction. Hence, it should be used in only acidic or neutral granulation. It can be
successfully used with ascorbic acid, multivitamin formulations and acid salts of organic
bases.
Alginic acid at a concentration of between 5-10% is an effective, but very expensive
disintegrant.
ION-EXCHANGE RESIN (AMBERLITE 88)
It has disintegrant properties at a concentration of between 1-5%. But this type of disintegrant
is rarely used.
It has highest water uptake capacity than other disintegrating agents like starch . It has
tendency to adsorb certain drugs.
16
17. 17
ADVANTAGES
Faster therapeutic effect
They have good compressability and flow property with poor gel formation.
Used in oral disintegrating dosage forms and mouth dissolving tablets.
DISADVANTAGES
Some are more hygroscopic in nature.
Some are anionic and may cause in – vitro binding.
18. CONCLUSION
Diluents are used for better compressability and flowability for obtaining better dosage form
with no toxicity. hence diluents should have ideal properties for selection. these are also used
in vaccine preparation for long storage. therefore, plays an important role in pharmaceutical
formulations.
Disintegrants are an essential component to tablet formulations. The ability to interact strongly
with water is essential to disintegrant function. Disintegration by capillary action or by
swelling is the major mechanism for disintegrants. Disintegrant can be added intragranular or
extragranular.
18
19. REFERENCES
The Theory And Practice Of Industrial Pharmacy By Leon
Lachman,a.Lieberman.
Wikipedia.Org/Wiki/Diluent
Wikipedia.Org/Wiki/Disintegrants
Carterpharmaceuticalconsulting.Com/Articles/The-role-of-
disintergrants.Html
Pharmainfo.Net/Tablet-disintegrants
http://formulation.vinensia.com/2011/11/diluents-fillers-for-
tablet-formulation.html
19
