In Process Quality

Control Tests for

Tablets
 IPQC Tests For Tablets:
• Hardness
• Friability
• Thickness
• Disintegration
• Weight variation
• Content uniformity
• Dissolution
• Leakage testing for strip
and blister packaging
 The general appearance
of a tablet is its visual identity and overall elegance. It
is essential for consumer acceptance, for control of lot-
to-lot uniformity. Appearance of a tablet involved the
following features:-
 Size
 Shape
 Colour
 Odour
 Taste
 Surface texture
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Many pharmaceutical tablets use color as a
vital means of rapid identification and
consumer acceptance
The color of a product must be uniform within a
single tablets

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Caliper scale 7
• Tablets require a certain amount of strength, or hardness and
resistance to friability, to withstand mechanical shocks of
handling in manufacture, packing and shipping

Hardness thus sometimes termed the tablet crushing strength

Tablet hardness tester are:-

Monsanto tester
Pfizer tester
Strong-cobb tester
Erweka tester
Schleuniger tester
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 Why do we measure hardness?
1. To determine the need for pressure adjustments on the
tableting machine.
2. Hardness can affect the disintegration. So if the tablet is too
hard, it may not disintegrate in the required period of time.
And if the tablet is too soft, it will not withstand the handling
during subsequent processing such as coating or packaging.
3. In general, if the tablet hardness is too high, we first check its
disintegration before rejecting the batch. And if the
disintegration is within limit, we accept the batch.
 Factors Affecting the Hardness:

1. Compression of the tablet and compressive force.

2. Amount of binder. (More binder = more hardness)
3. Method of granulation in preparing the tablet
(wet method gives more hardness than direct
method, Slugging method gives the best
hardness).
• Limits: 5 kg/cm2 minimum and 8 kg/cm2 maximum.
• Also expressed as Newton (N)

• Perform hardness test on 5 tablets and then take the average

hardness
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1. It is the tendency of tablets to powder, chip, or fragment and
this can affect the elegance, appearance, consumer
acceptance of the tablet.
2. Friability is a property that is related to the hardness of the
tablet.
3. An instrument called friabilator is used to evaluate the
ability of the tablet to withstand abrasion in packaging,
handling, and shipping.
4. Commonly used friabilator in industries is Roche Friabilator.

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 The friability test is official in USP but not in BP and IP

Procedure:
1. Weigh the tablet of weight 6.5 gm = W1
2. Put these tablets in the friabilator and adjust the
instrument at 100 revolutions (i.e. = 25 rpm for 4
min)
3. Remove the tablets, dedust and weigh again= W2
4. Friability (% loss) = W1-W2/ W1 X 100

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Roche friabilator
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Official Test
1. The volumetric fill of the die cavity determines the weight
of the compressed tablet. The weight of the tablet is the
quantity of the granulation that contains the labeled
amount of the therapeutic ingredient.
2. After the tablet machine in operation the weights of the
tablets are routinely checked to ensure that proper tablet
weights are made.
Procedure :
1. Take 20 tablets
2. Determine the individual weights of each tablets
3. Take average weights of 20 tablets
4. Compare the individual weight of tablets with avg weight.
5. Not more than 2 tablets should deviate from avg weight
by percent deviation as shown in table and
6. none should deviate more than 2 times the percentage
deviation limit.
Weight Variation limit for Tablet
 This test is done to ensure that every tablet contains the amount
of intended drug substance, with or without little variation in a
batch.
 This test is applicable to tablets that contain less than 10 mg or
less than 10 %w/w of the active ingredient.
 It is not applicable to tablets containing multivitamin and trace
element.
 The amount of active ingredient is determined by the Assay
method which is mentioned in its monograph.
 The result should lies within the range for the content of active
ingredient stated in the monograph. 20
Monograph of Paracetamol Tablet
 Content Uniformity as per IP

• Take 10 tablets randomly from the bulk of tablets.

• Determine the content of active ingredient in each tablet.
• Compare the individual content with labelled amount.
• The sample passes the test, if not more than one of the
individual value is outside the limit of 85 to 115% of the
labelled amount.
• And none should be outside the limit of 75 to 125% of the
label content.

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If two or three of the individual tablets are outside limits 85 to
115% of the average value and the none is the outside the limit
75 to 125%.

The test is repeated using another 20 tablets.

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 In the total sample of 30 tablets

Not more than three of the individual values are

outsides the limit 85 to 115% and none is outside the
limits 75 to 125% of the labelled content.

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Summarise Procedure :

1. In this test 30 tablets are randomly selected for the sample

and at least 10 of them assayed individually.

2. 9 of the 10 tablets must contain not less than 85% or more

than 115 % of labelled drug content.

3. 10th tablet may not contain less than 75% or more than
125% of labelled content .

4. If this conditions are not met the tablet remaining from the
30 must be assayed individually and none may fall outside
85 to 115 %.
3. Disintegration Test

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24
1. The disintegration USP device
uses 6 glass tubes
2. Tubes are 3 inches long having
opening at its top, and
3. held against a 10 mesh screen at
the bottom end of the basket rack
assembly.
4. Frequency of basket is 28-32
cycles/min .
5. The test is done on 6 tablets and
the test is passed when all the 6
tablets disintegrate.
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30
 Disintegration time (min)

Type of IP BP USP
tablet

Un coated 15 15 5
Coated 60 30 _
Film 30 _ _
Enteric 120 _ 1+2hr
Dispersible 3 3 3

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 Dissolution test
• Dissolution is the process by which a solid solute enters a
solution.

• In the pharmaceutical industry, it may be defined as the amount

of drug substance that goes into solution per unit time under
standardized conditions of liquid/solid interface, temperature
and solvent composition.

• Dissolution is considered one of the most important quality

control tests performed on pharmaceutical dosage forms.
 Dissolution test
• Now it developing into a tool for predicting bioavailability, and in
some cases, replacing clinical studies to determine
bioequivalence.

• Dissolution behavior of drugs has a significant effect on their

pharmacological activity.

• In fact, a direct relationship between in vitro dissolution rate of

many drugs and their bioavailability has been demonstrated.

• It is generally referred to as in vitro-in vivo correlation (IVIVC)

 Commonly Used Dissolution Media

1. Purified water

2. Dilute acid (0.001N – 0.1N HCl)

3. Stimulated gastric fluid

4. Stimulated intestinal fluid

5. Surfactants (e.g. Polysorbate, SLS)

6. Aqueous buffers (pH 5-7)

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 Apparatus-1 (Basket Type)
• A single tablet is placed in a small wire mesh basket attached to
the bottom of the shaft connected to a variable speed motor.
• The basket is immersed in a dissolution medium contained in a
1000 ml flask. The flask is cylindrical with a hemispherical
bottom.
• The flask is maintained at 37±0.5˚ C by a constant temperature
bath.
• The motor is adjusted to turn at the specified speed and sample
of the fluid are withdrawn at intervals to determine the amount
of drug in solutions.
 Apparatus-2 (Paddle Type )
• It is same as apparatus-1, except the basket is replaced by a
paddle.
• The dosage form is allowed to sink to the bottom of the flask
before stirring.
• For dissolution test U.S.P. specifies the dissolution test medium
and volume, type of apparatus to be used, rpm of the shaft, time
limit of the test and assay procedure for the API.
• The test tolerance is expressed as a % of the labeled amount of
drug dissolved in the time limit
• Unless otherwise specified in the individual monograph, the
requirements are met if the quantities of active ingredient dissolved
from the dosage units tested confirm to Acceptance Table. Continue
testing through the three stages unless the results confirm at either S1 or
S2.

the 5%, 15%, and 25% values in Acceptance Table 1 are percentages of the labeled
content so that these values and Q are in the same terms.
 Classification Of Dissolution Apparatus

• USP Dissolution Apparatus (Non-Official):

1. Rotating Bottle Apparatus

2. Diffusion Cell
3. Peristalsis Cell
4. Intrinsic Dissolution Method

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43
 Dissolution Apparatus-1 (Rotating
Basket)

DESIGN:
 Vessel: -Made of borosilicate glass.
-Semi hemispherical bottom
-Capacity 1000ml
 Shaft : -Stainless steel 316
-Speed 50-100 rpm.
 Water bath :-Maintained at 37±0.5ºC
 Dosage form is kept in basket.
USE: Tablets, capsules, floating dosage forms.

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 Dissolution Apparatus-2 (Paddle)

DESIGN:
 Vessel: -Same as basket apparatus
 Shaft: - Fused with blade at bottom
 Stirring elements:- Coated with teflon
For laboratory purpose
stainless steel is used
 Rotation Speed:- 25-50 rpm
 Water-bath: -Maintains at 37±0.5°C
 Sinkers : -Platinum wire used to prevent
tablet/capsule from floating.
 Dosage form should remain at the bottom center of vessel
USE: Orally disintegrating tablets, Chewable tablets etc.
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 Dissolution Apparatus-3 (Reciprocating
Cylinder)

Design:
 Vessel: -Set Of Cylindrical Flat Bottom Glass Vessels
-Set Of Reciprocating Cylinders
-Stainless Steel Fittings.
 Agitation Type: -Reciprocating
(Upward & Downward)
 Volume Of Dissolution Medium:-200-250ml
 Water Bath:- Maintain At 37±0.5°c
 Dosage Form Is Placed In Cylinder
USE: Tablets, Beads, Controlled And
Extended Release Formulations.
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 Dissolution Apparatus-4 (Flow
Through Cell)

DESIGN:
 Reservoir :- For dissolution medium
 Pump :- Forces dissolution medium through cell (upward
direction)
-Flow rate 10-100ml/min
-Laminar flow is maintained
-Centrifugal pumps are not recommended
Water bath:- Maintained at 37±0.5°C

USE: Low solubility drugs, micro particulate, implants,

suppositories, controlled release formulations.
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Dissolution Apparatus-4 (Flow Through
Cell)

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 Dissolution Apparatus-5 (Paddle- Over-
disk)
DESIGN:
 Vessel & Shaft:- Same as paddle apparatus
 Rotation Speed:- 25-50 rpm
 Sample holder:-disk assembly that holds
product in such a way that release surface
is parallel with paddle blade
-Distance 25 ± 2 mm
-Samples are drawn between
surface of the medium &
the top of the paddle blade
Temperature:32 ± 0.5°C
USE: Transdermal products, emulsions.

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 Dissolution Apparatus-6 (Rotating Cylinder)

• DESIGN:
 Vessel:- Same as of basket apparatus
 Shaft & Cylinder:- Stainless steel
 Sample :- Mounted to cuprophan (inner porous cellulosic material) an
entire system is adhered to cylinder.
• - Dosage unit is placed in cylinder and release from side out.
 Rotation Speed:- 25-50 rpm
 Water-bath: maintained at 32±0.5°C
• USE:
• Mainly transdermal products

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 Dissolution Apparatus-7
(Reciprocating-holder)
shaft

DESIGN:
Vessel:- A set of cylindrical vessels connected to
each other
dissolution
Volume of dissolution medium 50-200 ml medium

holder

 Shaft
 Holder:- Spring holder/ Reciprocating disk/ constant temp
water bath
Teflon cylinder/ Acrylic rod
 Sample : - Placed on holders
 Agitation:- Reciprocating frequency 30 cycle/sec
 Water-bath:- Maintained at 32±0.5°C
USE:
Controlled release dosage form, non disintegrating oral formulations.

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 Leak testing for Strips and Blister packing :
1. Take the required number of strips/ blisters as mentioned in
annexure. Check the quality of strips/blisters for any damages.
2. Tie the collected strips / blisters with a rubber band.

3. Ensure that all strips / blisters are dipped in water and close the
lid.

4. Connect opening of the desiccator to the vacuum pump.

Apply a vacuum of 300 m m of Hg and close the knob of
thedesiccator.
5. Keep the vacuum for 30sec.
7. Release the vacuum by opening the knob of the desiccator slowly
and open the lid remove the strips / blisters.

8. Wipe out the traces of water from the strips / blisters byusing
lint free duster .

9. Open the pocket of strips by using scissors to remove the tablets

/ capsules.
10. Open theblisters manually.

11. Check for any traces of water inside the strips / blisters.

12.Number of tablets or capsules, which have become

wet,should not be more than 1%
Documentation