Department of Pharmacy

Industrial Pharmacy-1
Topic:
Formulation of Tablets

Presented by
Dr. Matte Kasi Viswanadh,
Associate Professor,
Dept. of Pharmaceutics
CREATED BY K. VICTOR BABU
 AIM OF THE SESSION

To familiarize students with the basic concept of

INSTRUCTIONAL OBJECTIVES

This Session is designed to:

1. Demonstrate
2. Describe
3. List out the
4. Describe the

LEARNING OUTCOMES

At the end of this session, you should be able to:

1. Define
2. Describe
3. Summarize

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 Tablet Ingredients/ Excipients
• In addition to active ingredients, tablet contains a number of inert materials known as additives
or excipients.
Different excipients are: Function of excipients

 Impart weight, accuracy, & volume.

 Diluent / Filler
 Improve solubility
 Binder and adhesive
 Increase stability
 Disintegrants
 Enhance bioavailability
 Lubricants and glidants
 Modifying drug release
 Colouring agents
 Assist product identification
 Flavoring agents
 Increase patient acceptability
 Sweetening agents
 Facilitate dosage form design

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 1. Diluents
 Diluents are fillers used to make required bulk of the tablet when the drug dosage itself is
inadequate to produce the
bulk.
 Second reason is to provide better tablet properties such as improve cohesion,
 to permit use of direct compression manufacturing or to promote flow.

A diluent should have following properties:

 They must be non-toxic and low cost.
 They must be commercially available in acceptable grade
 They must be physiologically inert, physically & chemically stable by themselves or in
combination with the drugs.
 They must be free from all microbial contamination.
 They should not alter the bioavailability of drug.
 They must be color compatible.
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 Characteristics of an ideal diluent
 They must be nontoxic and acceptable to the regulatory agencies in all countries where the product is to
be marketed.
 They must be commercially available in an acceptable grade in all countries where the product is to be
manufactured.
 They must be cheap compared to the active ingredients and must be physiologically inert.
 They must be chemically stable alone and/or in combination with the drug(s) and/or other tablet
components.
 They must be color-compatible (should not produce any off-color appearance).
 They must have no negative effects on the bioavailability of the drug(s) in the product

Commonly used tablet diluents-  Dibasic calcium phosphate dehydrate

 Lactose-anhydrous and spray dried lactose  Calcium sulphate dihydrate
 Directly compressed starch-Sta Rx 1500  Mannitol and Sorbitol
 Hydrolyzed starch-Emdex and Celutab  Sucrose- Sugartab, DiPac, Nutab
 Microcrystalline cellulose-Avicel (PH 101and PH 102)  Dextrose
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 Lactose
 Lactose is the most widely used diluent for tablet  When a wet granulation method is
formulation. employed, the hydrous form of lactose
 It is obtained in hydrous as well as anhydrous forms. should be used.
 The anhydrous form, picks up moisture when  Two grades of lactoses are commercially
exposed to elevated humidity. available:
 Such tablets should be packed in moisture- proof
(i)60 to 80 mesh – coarse
packets or containers.
(ii) 80 to 100 mesh – regular grade
Advantages: Disadvantages:
• Lactose has no reaction with most of the drugs. • Lactose reacts with amine drug bases in
presence of alkaline lubricants e.g. metal
• Lactose formulations show good release rates.
stearates (e.g. magnesium stearate) and
• Their granulationsare readily dried, and the gradually discolours (dark brown) with time
tablet due to the formation of furfualdehyde. This
• disintegration times of lactose tablets are not reaction is called Maillard reaction.
strongly sensitive to variations in tablet hardness.
• It is a low-cost diluent.
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 Calcium salts ((DCP/TCP)
Dibasic calcium phosphate dihydrate (or dicalcium orthophosphate) (DCP)
[CaHPO4, 2H2O], Calcium sulfate dihydrate (CaSO4 , 2H2O).

Advantages:
 Diluents that exist intheir common salt form as hydrates, containing appreciable bound water
as water of crystallization.
 This bound water of calcium sulfate is not released below 80 ℃.
 They possess very low concentration of unbound moisture.
 Hence, these salts are excellent diluents for water-sensitive drugs.
 It is superior to anhydrous diluent, which has a moderate to high moisture demand.

Disadvantages:
 Divalent cation (Ca++) form insoluble complexes and salts with number of amphoteric or acidic
functionality antibiotics, which generally reduces their absorption (which is also why milk should
not be co-administered with these drugs).
 For e.g., Tetracycline products made with calcium phosphate diluent had less than half the
bioavailability of the standard product.
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 Spray dried Lactose
Advantages:
 It is used for
direct
compression
(containing
drug + diluent
+ disintegrant +
lubricant).
 In addition to
the direct
compression
properties,
spray dried
lactose also has
good flow
characteristics.
 It can
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 Mannitol
Advantages
• Because of the negative heat of solution (cooling sensation in the mouth), its slow solubility, and its
pleasant feeling in the mouth, it is widely used in chewable tablets.
• It is relatively non-hygroscopic and can be used in vitamin formulations.
• Low calorie content and non-carcinogenic.
Disadvantages
• Costly and has poor flow characteristics and usually require high lubricant levels.

Sorbitol
• It is an optical isomer of mannitol and is sometimes combined with Mannitol formulations to
reduce the diluent cost.
Disadvantages:
- It is hygroscopic at humidities above 65%.

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 Sucrose
• Some sucrose based diluents are:
 Sugar tab– 90 to 93% sucrose + 7 to 10% invert sugar
 Di Pac – 97% sucrose + 3% modified dextrins
 Nu Tab– 95% sucrose + 4% invert sugar + small amount of corn starch + Mg-stearate
Advantages:
They are all used for direct compression.
Disadvantages:
• All are hygroscopic when exposed to elevated humidity.

Microcrystalline cellulose (MCC)

•Trade Name : Avicel – is a directly compression material
• Two grades are available PH (101 powder) & PH 102 (granules)

Advantages:
It acts as diluent and disintegrating agents.
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 2. Binders and Adhesives
 Agents used to impart cohesive qualities to the powdered material are referred to as binders or
granulators.

Objective of incorporating binders

 They impart a cohesiveness to the tablet formulation (both direct compression and wet
granulation method) which ensures the tablet remaining intact after compression.
 They improve the free-flowing qualities by the formation of granules of desired size and
hardness.

Methods of binder addition

 Method-I
 Binders are used in dry form in the powder and then moistened with a solvent (of the binder)
to form wet lumps.

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 Method-II
 Binders are often added in solution form. It requires lower concentration of binder.
 By Method-I the binder is not as effective in reaching and wetting each of the particles within the mass
of the powder.
 Each of the particle in a powder blend has a coating of adsorbed air on its surface, and it is this film of
air which must be penetrated before the powder can be wetted by the binder solution.
Method-III
 In direct compression method microcrystalline cellulose (MCC), dextrose, amylose and PVP are used –
those have good flow properties and cohesiveness as well.
 It has been postulated that MCC is a special form of cellulose fibril in which individual crystallites
are held together largely by hydrogen bonding.

 The disintegration of tablets containing the cellulose occurs via breaking intercrystallite bonds by
the disintegrating medium.

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 Starch paste:
 Corn starch is often used in the concentration of 10–20%.
 Method of preparation:- Corn starch is dispersed in cold purified water to make a 5 to 10% w/w
suspension and then warming in water both with continuous stirring until a translucent paste is
formed. (Actually hydrolysis of starch takes place.)
Liquid glucose:- 50% solution in water is fairly common binding agent.
Sucrose solution:-
 50% to 74% sugar solution is used as binder.
 They produce hard but brittle granules.
 Their cost is low.
Gelatin solution:
• 10–20% concentration aqueous solution
• Should be prepared freshly and added in warm condition other wise it will become solid.
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 Method of preparation
 The gelatin is dispersed in cold water and allowed to stand until hydrated.
 The hydrated mass is warmed in water bath to dissolve.
Cellulosic solutions
• HPMC (Hydroxy propyl methyl cellulose) Soluble in cold water.
Method of preparation:
 HPMC is dispersed in hot water, under agitation.
 The mixture is cooled as quickly as possible and as low temperature as possible.
• HEC (Hydroxy ethyl cellulose), HPC (Hydroxy propyl cellulose) are other successful
binders.
• PVP (Polyvinylpyrollidone) used as an aqueous or alcoholic solution, concentration 2%

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 Disintegrants
 A disintegrant is a substance or a mixture of substances, added to tablet to facilitate its breakup or
disintegration after administration in the GIT.

 The active ingredients must be released from the tablet matrix as efficiently as possible to allow
for its rapid dissolution.
 Disintegrants can be classified chemically as: starches, clays, celluloses, alginates, gums and
cross-linked polymers.
Starch
• Corn starch, potato starch.
• For their disintegrating effect, starches are added to the powder blends in dry state.
Mode of action:
• Starch has a great affinity for water and swells when moistened, thus facilitating the rupture of the
tablet matrix.
• Normally 5% w/w is suggested and for rapid disintegration, 10 – 15% w/w may be used.
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 Superdisintegrants
 Super disintegrants like Croscarmelose - cross linked cellulose, Crospovidone - cross linked
polyvinyl pyrrolidone and Sodium starch glycolate- cross linked starch Mode of action
 Croscarmelose swells 4 to 8 fold in less than 10 seconds
 Crospovidone acts by wicking or capillary action.
 Sodium starch glycolate swells 7 to 12 folds in less than 30 seconds.

Other materials
 Methyl cellulose, Agar, Bentonite, Cellulose, Alginic acid, Guargum, and Carboxymethyl cellulose.
 Sodium lauryl sulfate is a surfactant.
 It increases the rate of wetting of the tablet, thus decreases the disintegrating time.

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 4.Lubricant and Glidants
 Objectives:
 Prevents adhesion of the tablet material to the surface of dies and punches.
 Reduce inter-particular friction, improve the rate of flow of tablet granulation.
 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,
 Facilitate easy ejection of the tablets from the die cavity.
Example: Stearic acid, Stearic acid salt - Stearic acid, Magnesium stearate, Talc, PEG (Polyethylene glycols),
Surfactants.
 Glidants are intended to promote flow of granules or powder material by reducing the friction between the
particles. Example: Corn Starch – 5-10% conc., Talc-5% conc., Silica derivative - Colloidal silicas such as
Cab-O- Sil, Syloid, Aerosil in 0.25-3% conc.
 Antiadherents are used for the purpose of reducing the sticking or adhesion of any of the tablet
ingredients or powder to the faces of the punches or to the die wall.

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 5. Coloring agent
 Objectives of using colors that
(i) It makes the tablet more esthetic in appearance and
(ii) Colour helps the manufacturer to identify the product during its preparation.
 Colorants are obtained in two forms dyes and lakes.
 Dyes are dissolved in the binding solution prior to the granulating process.
 However, during drying their color may migrate to the surface and may produce mottling of the tablet. So
another approach is to adsorb the dye on starch or calcium sulfate from its aqueous solution; the resultant
powder is dried and blended with other ingredients.
 Color lakes are dyes which are adsorbed onto a hydrous oxide of a heavy metal (like aluminium) resulting
in an insoluble form of the dye.

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 6. Flavours and Sweeteners
 Flavours are usually limited to chewable tablets or other tablets intended to dissolve in the mouth.
 Flavor oils are added to tablet granulations in solvents, are dispersed on clays and other adsorbents or
are
emulsified in aqueous granulating agents (i.e. binder).
 The use of sweeteners is primarily limited to chewable tablets.
E.g. Sugar
Mannitol– 72% as sweet as sugar, cooling & mouth filling
effect Saccharin– Artificial sweetener, 500 times sweeter than
sucrose Disadvantages (i) it has a bitter after taste and (ii)
carcinogenic Cyclamate– either alone or with saccharin– it is
banned Aspartame (Searle) – widely replacing saccharin
 Disadvantage – lack of stability in presence of moisture

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 2.Binders and Adhesives: These materials are added either dry or in
wet‐ form to form granules or to form cohesive compacts for
directly compressed tablet.
Example: Acacia, tragacanth‐ Solution for 10‐25% Conc.
Cellulose derivatives‐ Methyl cellulose, Hydroxy propyl
methyl cellulose, Hydroxy propyl cellulose
Gelatin‐ 10‐20% solution
Glucose‐ 50% solution
Polyvinylpyrrolidone (PVP)‐ 2% conc.
Starch paste‐10‐20% solution
Sodium alginate Sorbitol
3.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
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 Superdisintegrants: Swells up to 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 10n fold with in 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

4. 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),
CREATED BY K. VICTOR BABU Surfactants
 5. Coloring agent: The use of colors and dyes in a tablet has
three purposes:

(1)Masking of off color drugs

(2)Product Identification
(3)Production of more elegant product
All coloring agents must be approved and certified by FDA. Two forms
of colors are used in tablet preparation – FD &C and D & C dyes.
These dyes are applied as solution in the granulating agent or Lake
form of these dyes. Lakes are dyes absorbed on hydrous oxide and
employed as dry powder coloring.
Example: FD & C yellow 6‐sunset
yellow FD & C yellow 5‐ Tartrazine
FD & C green 3‐ Fast Green
FD & C blue 1‐ Brilliant
Blue
FD & C blue 2 ‐ Indigo
carmine D & C red 3‐
Erythrosine.
CREATED BY K. VICTOR BABU D & C red 22 – Eosin Y
 6.Flavoring agents: For chewable
tablet‐ flavor oil are used

7.Sweetening agents: For chewable

tablets: Sugar, mannitol.
Saccharine (artificial): 500 time’s
sweeter than sucrose
Disadvantage: Bitter aftertaste and
carcinogenic Aspartame (artificial)

Disadvantage: Lack of stability in

presence of moisture.

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 SELF-ASSESSMENT QUESTIONS

1. …

(a) …
(b) …
(c) …
(d) …

2. ….

(a) …
(b) …
(c) …
(d) …

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 TERMINAL QUESTIONS

1. Describe

2. List out

3. Analyze

4. Summarize

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 REFERENCES FOR FURTHER LEARNING OF THE SESSION

Reference Books:
1.
2.
3.

Sites and Web links:

1.
2.
3.

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 THANK YOU

Team – Course Name

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