Quality Control Tests for Solid

Dosage Forms
 Learning Points
• Physical tests: Hardness, Thickness and Diameter,
Friability, Disintegration, Weight Variation.

• Chemical tests: Content uniformity, Assay of active

ingredients and Dissolution tests of Powders,
Granules, Tablets and Capsules

• Significance of All the tests in Pharmaceutical

Quality Control
Weight variation (uniformity of weight)

• During production, sample tablets are

periodically removed for visual inspection and
automated physical measurement
• Weigh individually 20 units taken at random
and determine the average mass. Not more
than 2 tablets should deviate from the
average mass (BP2013)
Weight variation testing
 Weight Variation for Capsules
• Weigh an intact capsule. Open the capsule without
losing any part of the shell and remove the contents
as completely as possible.
• For soft shell capsules, wash the shell with a suitable
solvent and allow to stand until the odour of the
solvent is no longer perceptible.
• Weigh the shell.
• The mass of the contents is the difference between
the weighings. Repeat the procedure with another 19
capsules.
Weight Variation is Applicable for Following
Dosage Forms
 Friability
• A tablet’s durability may be determined through the use
of a friabilator. This apparatus determines the tablet’s
friability, or tendency to crumble, by allowing it to roll and
fall within the drum.
• The tablets are weighed before and after a specified
number of rotations and any weight loss is determined.
Resistance to loss of weight indicates the tablet’s ability to
withstand abrasion in handling, packaging, and shipment.
• A maximum weight loss of not more than 1% generally is
considered acceptable for most products.
• For tablets equal or less than 650 mg take a sample
of whole tablets equivalent to 6.5g weight.
• For more than 650 mg take 10 tablets.
• Rotate the drum 100 times (25 RPM).
• If tablet size or shape causes irregular tumbling,
adjust the drum base so that the base forms an angle
of about 10° with the horizontal and the tablets no
longer bind together when lying next to each other,
which prevents them from falling freely.
Friability
 Tablet Hardness
• Non-official tests. This test is intended to determine,
under defined conditions, the resistance to crushing
of tablets, measured by the force needed to disrupt
them by crushing.
• Hardness is the resistance of the tablet to chipping
abrasion or breakage under storage and
transportation and handling before usage.
• Special dedicated hardness testers or
multifunctional systems are used to measure
the degree of force (in kilograms, pounds)
required to break a tablet.
• A force of about 4 kg is considered the
minimum requirement for a satisfactory tablet.
Multifunctional automated equipment can
determine weight, hardness, thickness, and
diameter of the tablet.
Hardness Tester
 Tablet Thickness
• The thickness of a tablet is determined by the
diameter of the die, the amount of fill permitted to
enter the die, the compaction characteristics of the
fill material, and the force or pressure applied during
compression.
• To produce tablets of uniform thickness during and
between batch productions for the same formulation,
care must be exercised to employ the same factors of
fill, die, and pressure. The degree of pressure affects
not only thickness but also hardness of the tablet
 Content Uniformity
• The test for uniformity of content of single-dose
preparations is based on the assay of the individual contents
of active substance(s) of a number of single-dose units to
determine whether the individual contents are within limits
set with reference to the average content of the sample.
• The test is not required for multivitamin and trace-element
preparations and in other justified and authorised
circumstances.
• Method. Using a suitable analytical method, determine the
individual contents of active substance(s) of 10 dosage units
taken at random.
 Content Uniformity

• Determining the amount of drug in a sample of tablets (10 ).

• The average drug content is calculated.
• The content of the individual tablets should fall within
specified limits in terms of % deviation from the mean (90 –
110%). If not comply, repeat using 20 more tablets. (USP
Pharmacopeia)

• If content uniformity test is required, the Content uniformity

test is not required.
 Test A: Tablets, powders for parenteral administration,
ophthalmic inserts, suspensions for injection. (BP Pharmacopiea)

• The preparation complies with the test if each individual content is

between 85 percent and 115 percent of the average content.
• The preparation fails to comply with the test if more than one
individual content is outside these limits or if one individual content
is outside the limits of 75 per cent to 125 per cent of the average
content.
• If one individual content is outside the limits of 85 per cent to 115
per cent but within the limits of 75 per cent to 125 per cent,
determine the individual contents of another 20 dosage units taken
at random.
• The preparation complies with the test if not more than one of the
individual contents of the 30 units is outside 85 per cent to 115 per
cent of the average content and none is outside the limits of 75 per
cent to 125 per cent of the average content.
 Test B: Capsules, powders other than for parenteral
administration,
granules, suppositories, pessaries.
• The preparation complies with the test if not more than one individual
content is outside the limits of 85 per cent to 115 per cent of the average
content and none is outside the limits of 75 per cent to 125 per cent of
the average content.
• The preparation fails to comply with the test if more than 3 individual
contents are outside the limits of 85 per cent to 115 per cent of the
average content or if one or more individual contents are outside the
limits of 75 per cent to 125 per cent of the average content.
• If 2 or 3 individual contents are outside the limits of 85 percent to 115 per
cent but within the limits of 75 per cent to 125 per cent, determine the
individual contents of another 20 dosage units taken at random.
• The preparation complies with the test if not more than 3 individual
contents of the 30 units are outside the limits of 85 per cent to 115 per
cent of the average content and none is outside the limits of 75 percent to
125 per cent of the average content.
 Test C: Transdermal patches
• The preparation complies with the test if the
average content of the 10 dosage units is
between 90 percent and 110 percent of the
content stated on the label and if the
individual content of each dosage unit is
between 75 percent and 125 percent of the
average content.
What Happens to Tablet/Capsules after taken
orally?
 Disintegration
• For the medicinal agent in a tablet to become
fully available for absorption, the tablet must
first disintegrate and discharge the drug to the
body fluids for dissolution.
• In these instances, tablet disintegration
provides drug particles with an increased
surface area for activity within the
gastrointestinal tract
 Apparatus
• The apparatus consists of a basket and rack
assembly containing six open-ended
transparent tubes of USP-specified
dimensions, held vertically upon a 10-mesh
stainless steel wire screen
• During testing, a tablet is placed in each of the six tubes of the
basket, and through the use of a mechanical device, the basket
is raised and lowered in the immersion fluid at 29 to 32 cycles
per minute, the wire screen always below the level of the fluid.
• For uncoated tablets, buccal tablets, and sublingual tablets,
water at about 37°C serves as the immersion fluid unless
another fluid is specified in the individual monograph.
• For these tests, complete disintegration is defined as “that
state in which any residue of the unit, except fragments of
insoluble coating or capsule shell, remaining on the screen of
the test apparatus is a soft mass having no palpably firm core”
 The disintegration apparatus

A cylindrical disk of transparent plastic is also

used if specified in monograph.

Six tubes opened at the upper end and closed by a screen at the lower
• Tablets must disintegrate within the times set forth in the
individual monograph, usually 30 minutes, but varying from
about 2 minutes for nitroglycerin tablets to up to 4 hours for
buccal tablets. If one or more tablets fail to disintegrate,
additional tests prescribed by the USP must be performed.
• Enteric-coated tablets are similarly tested, except that the
tablets are tested in simulated gastric fluid, after which no sign
of disintegration, cracking, or softening must be seen. They are
then actively immersed in the simulated intestinal fluid for the
time stated in the individual monograph, during which time the
tablets disintegrate completely for a positive test.
• The simulated gastric fluid (0.1N HCl) for
specific time (2hr in B.P. and 1 hr in USP) for
a positive test, after which no signs of
disintegration, cracking or softening must be
seen, followed by immersion in stimulated
intestinal fluid (Phosphate buffer pH 6.8) for
the time stated in the individual monograph,
during which time the tablets disintegrate
completely.
 Limits According to BP
• If 1 or 2 dosage units fail to disintegrate,
repeat the test on 12 additional dosage units.
The requirements of the test are met if not
less than 16 of the 18 dosage units tested
have disintegrated
Disintegration
 Dissolution
• Dissolution testing is routinely used to provide critical in vitro
 drug release information for both quality control purposes,
i.e., to assess batch-to-batch consistency of solid oral dosage
forms such as tablets, and drug development, i.e., to predict 
in vivo drug release profiles
Simulated Dissolution Fluids
 Apparatus
• The equipment consists of (a) a variable speed stirrer motor;
(b) a cylindrical stainless steel basket on a stirrer shaft (USP
Apparatus 1) or a paddle as the stirring element (USP
Apparatus 2); (c) a 1,000-mL vessel of glass or other inert
transparent material fi tted with a cover having a center port
for the shaft of the stirrer and three additional ports, two for
removal of samples and one for a thermometer; and (d) a
water bath to maintain the temperature of the dissolution
medium in the vessel. For use of USP Apparatus 1, the
dosage unit is placed inside the basket. For use of USP
Apparatus 2, the dosage unit is placed in the vessel.
• In each test, a volume of the dissolution medium
(as stated in the individual monograph) is placed
in the vessel and allowed to come to 37°C ±
0.5°C. Then the stirrer is rotated at the speed
specified, and at stated intervals, samples of the
medium are withdrawn for chemical analysis of
the proportion of drug dissolved. The tablet or
capsule must meet the stated monograph
requirement for rate of dissolution, for example,
Drug Release
Dissolution
 DISSOLUTION TEST APPARATUS
I.P. USP B.P. E.P.
Paddle Basket Basket Paddle
Type 1 apparatus apparatus apparatus apparatus
Basket Paddle Paddle Basket
Type 2 apparatus apparatus apparatus apparatus
Reciprocating Flow through cell Flow through
Type 3 cylinder apparatus cell apparatus
Flow through
Type 4 cell apparatus
Paddle over
Type 5 disk
Rotating
Type 6 Cylinder
Reciprocating
Type 7 holder 41
USP APPARATUS 1 : BASKET TYPE
Design:
Vessel:-
 semi hemispherical bottom
 Capacity: 1000ml
Shaft:-
 Stainless steel 316
 Rotates smoothly without significance wooble
Basket:-
 Stainless steel 316
 Gold coatings up to 0.0001 inch
Water bath:- Maintained at 37± 0.5˚c

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• Dosage form contained
within basket
• Dissolution should occur
within Basket
• pH change by media
exchange
• Uses: Capsules, tablets,
delayed release,
suppositories, floating
dosage forms.
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• • Drug product
– Solids (mostly floating)
• Monodisperse (tablets)
• Polydisperse (encapsulated beads)
• Agitation
– Rotating stirrer
– Usual speed: 50 to 100 rpm
• Disadvantage
– Formulation may clog to 40 mesh screen
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APPARATUS 2: PADDLE TYPE
Design:
1. vessel: 1000 mL capacity, made of inert transparent
material.
2. Shaft: the blade passes through shaft so that bottom of
blade fuses with bottom of shaft.
3. Stirring elements:- made of tefflon
for laboratory purpose
Stainless steel 316
4. Water bath : maintain at 37± 0.5˚c.
5. sinkers: platinum wire used to prevent capsule/tablet
from floating
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• Dosage form should remain at
the bottom centre of the vessel

• Useful for :
• – Tablets

• pH change by media addition

• • Drug product
– Solids (mostly non floating)
• Monodisperse (tablets)
• Polydisperse
(encapsulated beads)

• • Agitation
– Rotating stirrer
– Usual speed: 25 to 100 rpm

• Standard volume: 900/1000 ml 46

Polyethylenefluroethylene / Teflon

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APPARATUS 3: RECIPROCATING CYLINDER
Design:
1.vessel: cylindrical flat bottom glass vessel.
2.Agitation type: -reciprocating
-generally 5-35 rpm
3. Volume of dissolution fluids: 200-250 ml
4. Water bath: maintain at 37±0.5˚c
5. Use: extended release

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APPARATUS 3: RECIPROCATING CYLINDER
The assembly consists of a set of
cylindrical, flat-bottomed glass
vessels; a set of glass
reciprocating cylinders; )stainless
steel fittings (type 316 or
equivalent) and screens that are
made of suitable nonsorbing and
nonreactive material and that are
designed to fit the tops and
bottoms of the reciprocating
cylinders; and a motor and drive
assembly to reciprocate the
cylinders vertically inside the
vessels

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• The vessels are partially immersed in a suitable water bath of
any convenient size that permits holding the temperature at
37 ± 0.5 during the test.
• The dosage unit is placed in reciprocating cylinder & the
cylinder is allowed to move in upward and downward
direction constantly. Release of drug into solvent within the
cylinder measured.
• Useful for: Tablets, Beads, controlled release formulations
• Standard volume: 200-250 ml/station
• Speed: 5-30 RPM

• Disadvantages: 1) small volume (max. 250 ml)

2) Little experience
3) Limited data

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Apparatus 3 – Reciprocating cylinder

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APPARATUS 4 : FLOW THROUGH CELL
Design:
1. Reservoir: for dissolution medium
2. Pump: - forces dissolution medium through cell
 Holding a sample
 Flow rate 10-100 ml/min
 Laminar flow is maintained
3. Water bath: maintain at 37± 0.5˚c

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USP APPARATUS 4 - FLOW THROUGH CELL

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Tablets 12 mm Tablets 22,6 mm Powders / Granules Implants Suppositories /
Soft gelatine capsules

• Useful for: Low solubility drugs, Micro particulates, Implants,

Suppositories, Controlledrelease formulations
• Advantages:
• 1. Easy to change media pH2. PH-profile possible
• 3. Sink conditions
• Disadvantages:
• 1. Deaeration necessary
• 2. High volumes of media
• 3. Labor intensive
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APPARATUS 5: PADDLE OVER DISK

Design
1. Vessel:
2. Shaft:
3. Stirring elements
4. Sample holder: - Disk assembly that hold the
product in such a way that release surface is
parallel with paddle.
5. Paddle is directly attached over disk assembly.
6. Samples are drawn away b/w the surface of
medium and top of paddle blade.
7. Volume; 900ml
8. Temperature; 32˚c
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USP APPARATUS 5 - PADDLE OVER DISK

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• Use the paddle and vessel assembly from Apparatus 2 with the addition of
a stainless steel disk assembly designed for holding the transdermal
system at the bottom of the vessel.
• The disk assembly holds the system flat and is positioned such that the
release surface is parallel with the bottom of the paddle blade
• The vessel may be covered during the test to minimize evaporation. Useful
for: Transdermal patches
• Standard volume: 900 ml
• Disadvantages: Disk assembly restricts the patch size.
Borosilicate Glass
17 mesh is standard (others available)
Accommodates patches of up to 90mm 57
APPARATUS 6: ROTATING CYLINDER

Design;
1. Vessel: in place of basket cylinder is used.
2. Cylinder : stainless steel 316.
3.Sample: - mounted to cuprophan(inner porous cellulosic
material) an entire system is adhere to cylinder.
-Dosage unit is place in cylinder and released
from outside.
4. Water bath : maintain at 32±.0.5˚c
Use : transdermal patches can not be cut into small size.

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• Use the vessel assembly from Apparatus 1 except to replace the
basket and shaft with a stainless steel cylinder stirring element
• The temperature is maintained at 32°C ± 0.5°C
• The dosage unit is placed on the cylinder with release side out
• The dosage unit is placed on the cylinder at the beginning of each
test, to the exterior of the cylinder such that the long axis of the
system fits around the circumference of the cylinder & removes
trapped air bubbles.
• Place the cylinder in the apparatus, and immediately rotate at the
rate specified in the individual monograph.

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APPARATUS 7; RECIPROCATING DISK
1.vessel : - flat bottom cylindrical vessel
- Volume of dissolution medium 50 -200 ml
2. Shaft:
3. Sample: - placed on disk shaped holders.
4. Agitation: - Reciprocation
- Reciprocating frequency 30 cycles/min.
5. Water bath: - Maintain at 32±0.5˚c
use: transdermal patches

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USP APPARATUS 7 – RECIPROCATING HOLDER

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• The assembly consists of a set of volumetrically calibrated
solution containers made of glass or other suitable inert
material, a motor and drive assembly to reciprocate the
system vertically
• The temperature is maintained at 32°C ± 0.5°C
• The dosage unit is placed on the cylinder with release side out
The solution containers are partially immersed in a suitable
water bath of any convenient size that permits maintaining
the temperature, inside the containers at 32 ± 0.5 For Coated
tablet drug delivery system attach each system to be tested to
a suitable Sample holder

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 References
• British pharmacopoeia (BP) 2013
• USP 35-NF30
• Remington: The Science and Practice of Pharmacy.
21st edition
• Pharmaceutical Quality Assurance in Class Industry
and Market. By Dr Karmat A Javaid
• The Theory and Practice of Industrial Pharmacy 3rd
Edition By Leon Lachman.