USP <905> Uniformity of Dosage Units

Dissolution Acceptance Criteria

Acceptance Criteria

Number

Tested

Stage

________________________________________

6

S1

Each unit is not less than Q + 5

________________________________________

USP <905> Uniformity of Dosage Units

USP <711> Dissolution

6

S2

Average of 12 units

(S1 + S2) is equal to or greater than Q, and no unit is less than Q - 15%

________________________________________

12

S3

Dissolution Example

Average of 24 units

(S1 + S2 + S3)

is equal to or greater than Q,

not more than 2 units are less

than Q - 15%, and no unit

is less than Q-25%

Passes

stage 1 ?

______________________________

Q

Results

(n=6)

Acceptance

criteria as per

specification

Acceptance criteria

for each unit

is not less than Q + 5

________________________________________

N

NLT 80% (Q)

85%

80%

81, 84, 88,

90, 90, 92

________________________________________

75%

NLT 80%

Y

80%

81, 84, 88,

90, 90, 92

________________________________________

Example 2

Stage 1: AV = 17.0 for 10 units tested.

This result is more than the limit L1 (15.0) therefore Stage 1 fails and we tested 20 more units.

Stage 2: AV = 14.0 (for n=30)

One result is 73% which is outside the range 76.125 and 126.875%, therefore Stage 2 fails the acceptance criteria.

Example 1

Q: Stage 1: AV = 16.4 for 10 units tested (average %LC is 105.9). This result is more than the limit L1 (15.0) and we tested 20 more units.

Stage 2: AV = 17.2 (for n=30). Does this pass the test because the AV is less than L2 (25.0) and no result is less than (1 – (0.01)(L2))M, (76.125%), and no result is greater than

(1+(0.01)(L2))M, (126.875%)?

A: The limit for the Acceptance Value is 15.0 at both levels of the test. L2 is only used to determine the acceptable range of individual values observed when 30 units have been analyzed. Where the average result is more than 101.5% LC then M has the value of 101.5% and the range is calculated as in the question.

where L2 = 25.0

Acceptance Criteria

How to use reference value M:

_

• Stage 1 : AV < 15.0 (L1) (for first 10 units)

_

If 98.5% < X < 101.5% then M=X

If X <98.5% then M=98.5%

If X > 101.5% then M=101.5%

_

If the acceptance value is > L1 (15.0), test another

20 units (stage 2) and calculate the acceptance value (for n=30).

• Stage 2 : AV < 15.0 (L1) (for 30 dosage units) and

_

_

(1-(0.01)(L2))M < each dosage unit < (1+(0.01)(L2))M

0.75M < each dosage unit < 1.25M

_

Weight Variation

(where L2= 25.0)

Tablets

Weigh 10 tablets individually. Calculate the content expressed as percentage of label claim of each tablet from the weight of the individual tablet and the result of the Assay. Calculate the AV.

Hard Shell

Capsules

Weigh 10 capsules individually. Remove the contents of each capsule. Weigh the emptied shells individually and calculate for each capsule the net weight of its contents by subtracting the weight of the shell from the respective gross weight. Calculate the drug substance content of each capsule from the net weight of the individual capsule content and the result of the Assay. Calculate the AV.

The uniformity of dosage units can be demonstrated by either of two methods:

• Weight Variation (if > 25 mg and > 25% DL)

_

Applicable for the dosage forms containing 25 mg or more of a drug substance comprising 25% or more, by weight, of the dosage unit ( > 25 mg and > 25% DL)

_

• Content Uniformity (if < 25 mg or < 25% DL)

Applicable for the dosage forms containing < 25 mg or < 25% by weight of dosage unit