PHARMACEUTICS – VIA (Pharmaceutical Quality Management) THEORY

QUALITY CONTROL OF SOLID DOSAGE FORMS

Contents
 General appearance
 Mechanical strength of tablets
 Weight variation test

The following standards or quality control tests should be carried out on compressed
tablets.
 General appearance
 Weight variation test
 Mechanical strength of tablets
 Content uniformity
 Disintegration
 Dissolution

a) Physical tests: hardness, thickness, and diameter, friability, disintegration, weight

variation
b) Chemical test: content uniformity, assay of active ingredients and dissolution
tests of powders, granules, tablets and capsules

1. General appearance

Size and shape: large, small, oval, round, cube, triangle, etc.
Organoleptic properties: color, odor, texture, etc.

Physical tests:
1. UNIFORMITY OF DIAMETER – for uncoated tablets; investigated by measuring
the diameter of 20 randomly taken tablets and calculate the average diameter

LIMIT
a. If the stated diameter is less than 12.5 mm, a deviation of 5% of the average
diameter is allowed
 b. If the stated diameter exceeds 12.5 mm, a deviation of 3% of the average
diameter is allowed

2. UNIFORMITY OF THICKNESS – investigated by measuring the thickness of 20

randomly taken tablets and calculate the average thickness

LIMIT
a. A deviation of 5% of the average thickness is allowed

3. MECHANICAL STREGTH OF TABLETS – provides a measure of the bonding

potential of the material; the mechanical properties of pharmaceutical tablets are
quantifiable by: friability, hardness or crushing strength

FRIABILITY TEST FOR TABLETS

 measure of surface hardness;
 evaluate the ability of the tablet to withstand abrasion in packaging,
handling and shipping;
 the commonly used friabilator in laboratories is the roche friabilator; the
tablets are subjected to combined effects of abrasion and shock;
 investigated by measuring the friability of 10-20 randomly selected tablets;
 dedust the tablets and weigh them all together;
 record the weight and place the sample in friabilator;
 the instrument is operated for 100 revolutions after which the tablets are
dusted and reweighed;
 calculate the percent loss in weight due to shocks by using formula;
 % weight loss = W1 – W2 / W1 x 100
 w1 = weight of tablets before test, w2 = weight of tablets after test;
 conventional compressed tablets that lose less than 0.5% or 1% of weight
are considered acceptable

Sample Criteria
 for tablets with unit weight of equal to or less than 650 mg take a sample of
whole tablets corresponding as near as possible as 6.5 gram
HARDNESS TEST / UNIFORMITY IN THE HARDNESS OF TABLETS
 investigated by measuring the hardness of 10-20 randomly selected tablets and
calculate the average
 the result is measured in kg

LIMIT
 a deviation of +/-5% of the average value is allowed

Standard Values:
Oral tablets = 4-8/10 kg
Chewable/Hypodermic tablets = 3 kg
Sustained release tablets = 10-20 kg

TYPES OF HARDNESS TESTERS

 Monsanto hardness tester or stokes hardness tester
 Strong cobb tester
 Pfizer tester
 Erweka tester
 Schleuniger or heberlein tester

WEIGHT VARIATION TEST FOR TABLET

 Applicable when the tablet contains 50% or more of the drug substance

 Investigated by measuring weight of 20 randomly selected tablets and calculating

the average
  Out of 20 tablets tested 18 tablets must have weight within the limits specified in
the monograph
 2 tablets showing deviation must not deviate more than the double of percentage
allowed

LIMIT: USP

AVERAGE WEIGHT PERCENT DIFFERENCE

130 mg or less 10%
More than 130 mg through
7.5%
324 mg
More than 324 mg 5%

QUALITY CONTROL TESTS FOR POWDERS AND GRANULES

 Particle size
 Flow properties
 Moisture content
 Dissolution
 Assay

PARTICLE SIZE
 Can affect hardness, flow properties, rate of dissolution, weight variation
 Methods for determination of particle size:
 Sieving
 Microscopy
 Sedimentation
 Light energy diffraction
 Laser light scattering
 Electronic sensing zone

Sieving Method (Particle Size Distribution)

 A stack of different size sieves (sieve no. 40, 60, 80, 100, and 120) are placed
tightly one over the other in such a manner that each lower sieve has a small
aperture size than that of the sieve above it
 Below the lowest sieve is placed a collecting tray
 This assembly is placed on mechanical shaker. Sample of 50gm of the drug is
placed in the upper most sieve and the top is then closed with a lid
 Then the shaker is operated for 5 minutes. In this way the powders with different
particle sizes is collected on each sieve and stored separately
FLOW OF PROPERTIES

Angle of Repose
 Angle of repose is determined by funnel and cone method. The funnel is fixed in
place, 4 cm above the petri dish surface. Powder sample (5 gm) is poured
through funnel and a cone is built. The height of cone (h) and the radius (R) is
measured. The angle of repose is calculated as follows:

Angle of Repose = tan-1 h/R

Flow Property Angle of Repose (degrees)

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

Hausner Ratio (Index of flowability)

 First sample is poured into graduated cylinder (250 ml) up to 100 ml; this is the
bulk volume (Bv). After this the cylinder is tapped on flat surface for a while until
no further change could be observed in the volume. This is tapped volume (Tv).
 Then Hausner ratio is calculated by the following equation
 Hausner Ratio = Bv/Tv

Compressibility Index
 Compressibility index = (Bv-Tv/Bv) x 100
 Compressibility Index
Flow Character Hausner Ratio
(%)
< 10 Excellent 1.00 – 1.11
11-15 Good 1.12 – 1.18
16-20 Fair 1.19 – 1.25
21-25 Passable 1.26 – 1.34
26-31 Poor 1.35 – 1.45
32-37 Very poor 1.46 – 1.59
>38 Very, very poor >1.60

MOISTURE CONTENT

 The amount of moisture present in the granule is called moisture content

 Generally the granules contain 2% of the moisture. It is required for the binding of
the powders or granules during compression
 Determined by IR balance
 Sample placed in the balance and initial weight is determined
 IR bulb is initiated and the moisture is removed via heating
 Note the reading or final weight

 Percent fine - 15%

 Friability?