GENERAL TIPS

Types of Tablet:-

IP BP USP
Uncoated Uncoated Compressed/molded
Film Coated Coated Plain Coated
Enteric Coated Gastro Resistent (Enteric Delayed Release
Coated)
Dispersible Tablet Dispersible Tablet Dispersible Tablet
Modified Release Tablet Modified Release Tablet Exteded Release Tablet
Soluble Tablet Soluble Tablet Soluble Tablet
Effervescent Tablet Effervescent Tablet Effervescent Tablet
For use in mouth For use in mouth Chewable/Buccal,
(Chewable, Lozenges, (Chewable, Lozenges, Sublingual
Sublingual) Sublingual)
Orodispersible Orodispersible Orodispersible

Standards for Tablets:-

IP BP USP
Content of Active Content of Active Content of Active
Ingredient Ingredient Ingredient
Uniformity of weight Uniformity of weight Weight Variation
Uniformity of Content Uniformity of Content Uniformity of Content
DT DT DT
Dissolution Dissolution Dissolution

1) Content of Active Ingredient: - 1) Assay of Active

2) 20 tabs: - Limits 90% to 110%
2) Uniformity of Weight/Wt Variation:-
20 tabs, calculate avg. wt NMT 2 deviate, none twice the limits.

Weight Variation Limits:-

1) For Tablets 2) For Capsule:-
IP Limit
IP/BP Limit USP Less than 300mg 10%
80 mg or less 10% 130mg or less 300mg or More 7.5%
More than 80mg or 7.5% 130mg to 324mg
Less than 250mg

250mg or more 5% More than 324mg

Friability Test:- This test is additional to check crushing strength of tablet by this test
one can check Capping &/or Lamination. USP limit is 0.5 to 1%. Rotation: - 25 rpm or
100 rotations in 4 min.

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USP 29-now <905>Uniformity of Dosage Units
25 mg & 25% of active
ingredient

Uniformity of Content or Content Uniformity:-

IP: - Active less than 10mg or 10%,
BP:- Active less than 2 mg or 2%,
USP:- Active less than 25mg or 25%.
-10 tabs limit NMT 1 tab deviate 85 115% & none outside 75 125% of the Avg
value/IP/BP/USP (Relative Standard Deviation less than or equal to 6%),
- If 2 or 3 individual values are outside the limits 85 115% of the Avg value, & none
outside 75 125% repeat for 20 tabs.
- Complies when 30 tabs NMT 3 of the individual values are outside the limit 85 115%
of the Avg value, and none outside 75 125%.

Disintegration Time:-
Uncoated Tablet NMT 15 min, in water with Disc 370C 20C
Coated Tablet NMT 30 min, In water with Disc for Film Coated Tab, and
NMT 60 min Other than Film coated tablet
Enteric Coated Tab Intact for 1 hr in 0.1 N HCl & disintegrate within 2 hr in Mixed
6.8 Phosphate buffer. According to USP 1 hr in Simulated
gastric fluid, then in Simulated Intestinal Fluid.
Dispersible/Soluble Within 3 min in water at 250C 10C (IP) & 15 250C (BP)
Orodispersible Within 1 min
Effervescent Tab 5 min in 250 ml water at 20 300C (IP) & 5 min in 200 ml
water at 15-250C (BP)
Buccal & Sublingual Not Applicable but dissolve within 15 30 min.

DT Apparatus:- Mesh Apperture:- 2mm (#10), Cycles:- 28 32 cycles/min, 50 60 mm

distance from bottom & top, Temp of water 370C 20C. If 1 or 2 tabs fail, repeat for 12
tabs.

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Solubility:-

BP SOLUBILITIES
Very soluble less than 1 part
Freely soluble from 1 to 10 parts
Soluble from 10 to 30 parts
Sparingly soluble from 30 to 100 parts
Slightly soluble from 100 to 1000 parts
Very slightly soluble from 1000 to 10,000 parts
Practically insoluble more than 10,000 parts
Approximate quantity of solvent by volume for one part of soluble
by weight. For example, 1g of a very soluble substance dissolves
in less than 1ml of solvent (1gm/ml).

Compressibility Index (Carrs Index):- Angle of Repose:-

Tapped Density Bulk Density x 100 = tan-1(h/r)
Tapped Density

Flow property C.I (%) Hausner ratio

Excellent 10 1.00 1.11
Good 11 15 1.12 1.18
Fair 16 20 1.19 1.25
Passable 21 25 1.26 1.34
Poor 26 31 1.35 1.45
Very poor 32 37 1.46 1.59
Very, very poor >38 >1.60

Flow property Angle of repose (degrees)

Excellent 25 30
Good 31 35
Fair-aid not needed 36 40
Passable may hang up 41 45
Poor must agitate, 46 55
vibrate
Very poor 56 65
Very, very poor >66

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Bioavailability:- The rate and extent to which the active ingredient or active moiety is
absorbed from a drug product and becomes available at the site of action. For drug
products that are not intended to be absorbed into the bloodstream, bioavailability may be
assessed by measurements intended to reflect the rate and extent to which the active
ingredient or active moiety becomes available at the site of action.
ANDA - Abbreviated New Drug Application.
IND Investigational New Drug Application.
NDA New Drug Application.

According to the BCS, drug substances are classified as follows:

Class I - High Solubility, High Permeability

Class II - High Permeability, Low Solubility
Class III -High Solubility, Low Permeability
Class IV - , Low Solubility Low Permeability

A drug substance is considered HIGHLY SOLUBLE when the highest dose

strength is soluble in < 250 ml water over a pH range of 1 to 7.5.
A drug substance is considered HIGHLY PERMEABLE when the extent of
absorption in humans is determined to be > 90% of an administered dose, based
on mass-balance or in comparison to an intravenous reference dose.
A drug product is considered to be RAPIDLY DISSOLVING when > 85% of the
labeled amount of drug substance dissolves within 30 minutes using USP
apparatus I or II in a volume of < 900 ml buffer solutions.

DISSOLUTION DETERMINATION

USP apparatus I (basket) at 100 rpm or USP apparatus II (paddle) at 50 rpm.

Dissolution media (900 ml): 0.1 N HCl or simulated gastric fluid, pH 4.5 buffer,
and pH 6.8 buffer or simulated intestinal fluid.
Compare dissolution profiles of test and reference products using a similarity
factor (f2).

AN ARRAY OF TABLET TYPES

Immediate Release Uncoated Tablets: Usually no taste/stability issues.

Coated Tablets: For taste/stability/identification (coated with water-soluble/dispersible

polymermixture of hydroxypropyl cellulose/hydroxypropylmethyl cellulose); coating
readily ruptures in GI tract.

Enteric-Coated Tablets: For drugs inactivated or destroyed in the stomach or for those
causing irritation to the gastric mucosa; tablet passes through the stomach but
disintegrates in the intestines where absorption takes place. Excipients used for enteric
coating include cellulose acetate phthalate, mixtures of fats and fatty acids, etc.

Multiple Compressed Tablets: Multiple-layered tablets manufactured by using more

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than one compression cycle. Each layer contains a different drug and each may be
colored differently.

Controlled Release Tablets: Improved therapy, less toxicity, improved patient

complianceusing polymers such as methacrylates.

Sublingual Tablets: Small, flat ovals such as nitroglycerin. They are ideal tablets for
absorption of drugs which are destroyed by gastric juice or undergo first pass
metabolism.

Chewable Tablets: Disintegrate rapidly when chewed for patients with swallowing
difficulty (children, elderly) and when there is no access to water. Most commonly used
for multiple vitamins and antacids.

Effervescent Tablets: In addition to the active, this product form contains sodium
bicarbonate and citric acid. When water is added the ensuing chemical reaction forms
carbon dioxide, which acts as a disintegrant and produces effervescence that hastens
dissolution (antacids).
Official Standards as per I.P. / B.P. / U.S.P.
COMPARISON OF DIFFERENT PHARMACOPOEIAL QUALITY CONTROL TESTS

PHARMACOPOEIAS TYPE OF TABLET TESTS TO BE PERFORMED

BRITISH Content of active ingredients
PHARMACOPOEIA
Disintegration
For all tablets
Uniformity of content

Labeling
Disintegration test
Uncoated tablet
Uniformity of weight
Disintegration test
Effervescent tablet
Uniformity of weight
Coated tablet Disintegration test
Uniformity of weight
Gastro resistant
Disintegration test
tablet
Modified release
Uniformity of weight
tablet
Tablet for use in
Uniformity of weight
mouth
Soluble tablet Disintegration test
Uniformity of weight

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 Disintegration test

Dispersible tablet Uniformity of dispersion

Uniformity of weight
Uniformity of container content

Content of active ingredient

Uncoated tablet Uniformity of weight
Uniformity of content

Disintegration test
INDIAN Enteric coated tablet Disintegration test
PHARMACOPOEIA
Uniformity of dispersion
Dispersible tablet
Disintegration
Soluble tablet Disintegration test
Disintegration/ Dissolution /
Effervescent tablet Dispersion
test
Bulk density /Tapped density of
powder

Powder fineness
Loss on drying
Physical tests Disintegration test
UNITED STATES
applicable to tablet Tablet friability
PHARMACOPOEIA
formulation Dissolution test
Drug release testing
Uniformity of dosage form
Container permeation test

Labeling of inactive ingredients

Tablet Problems:-

Capping:- Capping is the term used, when the upper or lower segment of the tablet
separates horizontally, either partially or completely from the main body of a tablet and
comes off as a cap, during ejection from the tablet press, or during subsequent handling.

Lamination / Laminating:- Definition: Lamination is the separation of a tablet into

two or more distinct horizontal layers.

Chipping:- Chipping is defined as the breaking of tablet edges, while the tablet leaves
the press or during subsequent handling and coating operations.

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Cracking:- Small, fine cracks observed on the upper and lower central surface of
tablets, or very rarely on the sidewall are referred to as Cracks.

Sticking / Filming:- Sticking refers to the tablet material adhering to the die wall.
Filming is a slow form of sticking and is largely due to excess moisture in the
granulation.

Picking:- Picking is the term used when a small amount of material from a tablet is
sticking to and being removed off from the tablet-surface by a punch face.
The problem is more prevalent on the upper punch faces than on the lower ones. The
problem worsens, if tablets are repeatedly manufactured in this station of tooling because
of the more and more material getting added to the already stuck material on the punch
face.

Mottling:- Mottling is the term used to describe an unequal distribution of colour on a

tablet, with light or dark spots standing out in an otherwise uniform surface.

Double impression:- Double Impression involves only those punches, which have a
monogram or other engraving on them.

Problems for tablet coating:-

Blistering:- It is local detachment of film from the substrate forming blister.

Chipping: It is defect where the film becomes chipped and dented, usually at the edges
of the tablet.

Cratering: It is defect of film coating whereby volcanic-like craters appears exposing the
tablet surface.

Picking: It is defect where isolated areas of film are pulled away from the surface when
the tablet sticks together and then part.

Pitting: It is defect whereby pits occur in the surface of a tablet core without any visible
disruption of the film coating.

Blooming: It is defect where coating becomes dull immediately or after prolonged

storage at high temperatures.

Blushing: It is defect best described as whitish specks or haziness in the film.

Colour variation: A defect which involves variation in colour of the film.

Infilling: It is defect that renders the intagliations indistinctness.

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Orange peel/Roughness: It is surface defect resulting in the film being rough and
nonglossy. Appearance is similar to that of an orange.

Cracking/Splitting: It is defect in which the film either cracks across the crown of the
tablet (cracking) or splits around the edges of the tablet (Splitting).