BP Testing (Solid Dosage Forms)

Question 1

Examples of pharmacopoeial quality control tests for tablets

Answer 1

• Uniformity of weight (mass) (XII G, Ph. Eur. 2.9.5) BP Appendix
• 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)
• Constant dosing required
• However, small variations are acceptable, as defined in i.e. the BP / EP

Question 2

Uniformity of weight (mass)

Procedure:

Answer 2

1. Weigh 20 tablets selected at random and determine the average 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 one tablet weight may exceed the following values:

<80 ±10% ± 20%

80-250 ± 7.5% ± 15%

> 250 ± 5% ± 10%

Question 3

Uniformity of content Procedure:

Answer 3

1. Determine the active ingredient content of 10 tablets taken at random using a suitable analytical method.
2. PASS if all 10 values are all within the range 85-115% of the average tablet dose. FAIL if >1 tablet dose falls outside 85-115%.
3. If only one value is outside the limits 85-115% but within the limits 75- 125% of the average tablet dose, repeat the determination using another 20 tablets taken at random.
4. If, in the total sample of 30 tablets, no more than one individual value is outside the limits 85-115% and no tablet is outside the limits 75-125% of the average tablet dose = PASS.

Question 4

Disintegration

Procedure:

Answer 4

1. 6 tablets taken at random are placed individually in a tube. Repeat three times, so, a total of 18 tablets. You may need more if this results in a FAIL outcome.
2. The tubes are vertically raised and lowered 50-60 mm, 28-32 times a minute, in a water bath at 37°C. What media is used? Water?
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 μm) sieves at the base.

Question 5

Factors effecting dissolution

Answer 5

! Solubility of drug substance 
! Composition of media
! Temperature of media
! Factors that effect dissolution 
! Stirring
! Sink conditions
! Normally the concentration of the drug in the bulk of the dissolution media should not exceed 10% of the solubility.

Question 6

Dissolution testing - example

Procedure:

Answer 6

1. Individually place 3 - 6 tablets into a dissolution beaker containing 900ml buffer(36.5°C-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 buffer.
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.

Question 7

Resistance to crushing of tablets

Answer 7

Crushing strength = Hardness = The minimum diametric compressional force which fractures a tablet
- Tablet diameter and thickness affect the force necessary to break it.

Question 8

Crushing strength measurements

! Procedure:

Answer 8

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 max and min force measured, as well as information regarding the instrument and tablet orientation. Calculate the tensile strength of each tablet and the mean ± standard deviation.

Question 9

Crushing strength can be measured with different units

Answer 9

! Kilogram(kg)–The kilogramme 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

Question 10

Friability measurements Procedure:

Answer 10

1. If a single tablet weighs <0.65g, select 20 tablets at random. If a single tablet weighs > 0.65 g, select 10 tablets at random.
2. Tablets are de-dusted, weighed [W0], placed in a perspex drum (Copley Friabilator) and tumbled (rotated 100 times [4min]).
3. After de-dusting they are reweighed [W].
   F% = [W0 −W]/ W0 x 100
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. 5. Explain the clinical significance of high friability…

Question 11

% Friability =

Answer 11

% weight loss resulting from chipping, abrasion, and erosion of the tablets under stress conditions

Question 12

Tensile strength =

Answer 12

σ = 2P / πDH