Pharmacopoeial quality control

tests for tablets

Dr Fang Liu


Pharmacopoeial quality control tests for
tablets
Uniformity of weight (mass) (BP Appendix XII G, Ph. Eur.
2.9.5)
Uniformity of content (BP Appendix XII H, Ph. Eur. 2.9.6)
Disintegration test (BP Appendix XII A, Ph. Eur. 2.9.1)
Dissolution test (BP Appendix XII D, Ph. Eur. 2.9.3)
Resistance to Crushing of Tablets (BP Appendix XVII H,
Ph. Eur. 2.9.8)
Friability (BP Appendix XVII G, Ph. Eur. 2.9.7)


Uniformity of weight and content
Does the dosage form contain the correct amount of drug?

Is the drug content reproducible between tablets?

Is the manufacture of the dosage from reproducible?


IS THE PATIENT GOING TO RECEIVE THE
CORRECT AMOUNT OF DRUG FROM EACH
DOSE?
Uniformity of weight (mass)
Procedure:

1. Weigh 20 tablets selected at random and determine the average and
individual weight.

2. PASS if no more than two of the individual weights deviate from the
average weight by more than the percentage deviation shown in the
table and none may deviate by more than twice that percentage.

Average weight
of tablet [mg]
No more than 2 tablet
weights may deviate by:
No tablet weight may exceed
the following values:
<80
80-250
>250
10%
7.5%
5%
20%
15%
10%
Uniformity of content (flow diagram)
Determine drug content of 10 tablets and calculate the average tablet
dose
All tablets are within
85-115% of the
average tablet dose
More than one tablet
is outside 85-115% of
the average tablet
dose
FAIL
Only 1 tablet is
outside 85-115% of
the average tablet
dose
Is the tablet within the
limits 75-125% of the
average tablet dose?
Repeat with 20 further tablets.
In the total 30 tablets are all
tablets within 75-125% and no
more than 1 tablet outside 85-
115% of the average tablet
dose?
Yes
No
Yes
PASS
Determining drug content
Prepare tablets for analysis
Grind, dissolve and filter
Make up to known volume
Assay by comparing against suitable standards

UV absorbance

max
of drug
Calibration curve with known standards
Determining drug content
Prepare tablets for analysis
Grind, dissolve and filter
Make up to known volume
Assay by comparing against suitable standards

UV absorbance

max
of drug
Calibration curve with known standards
Disintegration and dissolution
Disintegration and dissolution testing
Will the tablet disperse and dissolve in the correct
environment?

Will the tablet disperse and dissolve in the optimum time?


WILL THE PATIENT BE ABLE TO ABSORB A
THERAPEUTIC DOSE OF THE DRUG?
Disintegration
Procedure:

1. 6 tablets taken at random are placed individually in a tube.
Repeat three times, so, a total of 18 tablets.

2. The tubes are vertically raised and lowered 50-60 mm, 28-32
times a minute, in a water bath.

3. PASS if all 18 tablets have completely
disintegrated within the specified time
(see table on next slide).
FAIL if any tablet has not disintegrated.



The method uses 2.8 cm diameter tubes fitted
with 10 # (1700 m) sieves at the base.
Disintegration testing parameters
Tablet type Standard Conditions
Uncoated <15min Water
Coated [film] <30min Water
Other Coated tablets <60min Water, if no disintegration occurrs
repeat the test on a further 6 tablets,
replacing water by 0.1M HCl

Enteric-coating >120min 0.1 M HCl. No disintegration
<60min pH 6.8 phosphate buffer

Effervescent <5min 200ml water at 20C
Soluble <3min Water at 20C

Dispersible <3min Place 2 tablets in 100 ml water at
20C and stir until completely
dispersed. A smooth dispersion is
produced which passes through a
sieve screen 22 # (710 m ).
Dissolution testing
Procedure:

1. Individually place 3 - 6 tablets into a dissolution
vessel containing 900 ml medium (36.5C-37.5
C). Set paddles or basket rotating at a defined
rpm.

2. Withdraw samples at 45 min, prescribed intervals or
continuously. Samples should be taken from a point
halfway between the surface and the top of the
paddle, not less than 10 mm from the vessel wall.

3. Replace volume with an equal amount of medium.

4. Determine the amount of active ingredient in the
sample. Pass if >70% has dissolved by 45 min. If
one fails, a further 6 tablets may be tested. To pass,
all must comply
Dissolution data interpretation
Shape of the dissolution graph can tell you a lot about the
nature of drug bioavailability and the controlling factors of
this process
The y-axis is usually
labelled as cumulative
drug dissolved (%) or
cumulative drug
released (%).
Determining drug content for dissolution
assays
Similar methodology to drug content analysis

Assay development using UV spectroscopy
Samples already in solution

max
of active
Calibration curve with known standards


Crushing and Friability Testing
How robust are the tablets?

Is the quality of the tablets reproducible?

Will the tablets withstand handling, processing
and transport?


WILL THE PATIENT RECEIVE A GOOD
QUALITY DOSAGE FORM DELIVERING 100%
OF THE INTENDED DOSE?


Crushing strength measurements
Procedure:

1. Select 10 tablets at random and place in a reproducible
manner between the jaws of the instrument. Denote
orientation of tablet with regard to shape, break marks or
inscriptions.

2. Apply pressure and measure the force at the break.

3. Expression of results:

Mean force is expressed in Newtons (N).

Also provide the maximum and minimum force measured,
as well as information regarding the instrument and tablet
orientation.

Calculate the tensile strength of each tablet and the mean
standard deviation.
Resistance to crushing of tablets
Crushing strength = Hardness = The minimum diametric
compression force required to fracture a tablet
Tablet diameter and thickness affect the force necessary to break it.

Tensile strength

Where o is the tensile strength (N/m
2
), P the crushing strength (N), D
the diameter (m) and H the tablet thickness (m)
Tensile strength is expressed in N/m
2
or Pa, MPa.

DH
P
t
o
2
=
Crushing strength measurements
Kilogram (kg) The kilogram is recognised by the SI system as the
primary unit of mass.

Newton (N) The Newton is the SI unit of force and is the unit that
should be used for tablet hardness testing. 9.807 Newtons = 1
kilogram.

Pound (lb) Technically a unit of mass but can also be used for
force and should be written as pound force or lbf in this case.
Sometimes used for tablet strength testing in North America, but it is
not an SI unit. 1 kilogram = 2.204 pounds
Friability: Resistance to abrasion
% Friability = % weight loss resulting from chipping, abrasion, and
erosion of the tablets under stress conditions
100 *
0
0
%
W
W W
F
(

=
Friability measurements
Procedure:
1. If a single tablet weighs < 0.65 g, select 20 tablets at random.
If a single tablet weighs > 0.65 g, select 10 tablets at random.

2. Tablets are de-dusted, weighed [W
0
], placed in a Perspex drum
(Copley Friabilator) and tumbled (rotated 100 times [4min]).

3. After de-dusting they are reweighed [W].

4. PASS if <1% friability (<0.1% is a realistic goal in development). If
>1%, repeat twice. The mean weight loss of all three must be <1%
to PASS.

Learning Outcomes
Introduction to pharmacopeial quality control tests for
tablets

Understand why quality control is necessary

Understand how to plan and conduct quality control
experiments for tablets