UNIFORMITY
OF DOSAGE UNITS
1. The
term “uniformity of dosage unit” is defined as the degree of uniformity in the
amount of the drug substance among dosage units.
2. Uniformity
of dosage unit ensures the consistency of dosage units, each unit in a batch
should have a drug substance content within a narrow range around the label
claim.
3. The
uniformity of dosage units specification is not intended to apply to
suspensions, emulsions, or gels in unit-dose containers intended for external,
cutaneous administration.
4. The
uniformity of dosage units can be demonstrated by either of two methods, Content
Uniformity or Weigh Variation.
5. The
test for Weight Variation is applicable for the following dosage forms:
Ø Solutions
enclosed in unit-dose containers and into soft capsules.
Ø Solids
(including powders, granules, and sterile solids) that arepackaged in
single-unit containers and contain no active or inactive added substances;
Ø Solids
(including sterile solids) that are packaged in single-unit containers, with or
without active or inactive added substances that have been prepared from true
solutions and freeze-dried in the final containers and are labeled to indicate
this method of preparation;
Ø Hard
capsules, uncoated tablets, or film-coated
tablets containing 25 mg or more of a drug substance comprising 25%or more by
weight of the dosage unit or, in the case of hard capsules, the capsule
contents, except that uniformity of other drug substances present in lesser proportions
is demonstrated by meeting the requirements for Content Uniformity.
6. The
test for Content Uniformity is applicable for the following dosage forms:
Ø Hard
capsules, uncoated tablets, or film-coated tablets containing less than 25 mg of
drug substance comprising less than 25%, by weight, of the dosage unit.
Ø Suspension,
emulsion or gels enclosed into soft capsules.
Ø Others
7. Select
not fewer than 30 units, and proceed as follows for the dosage form designated.
8. Assay
10 units individually using an appropriate analytical method and calculate the
acceptance value as content uniformity for uniformity of dosage unit
determination.
9. Carry
out an assay for the drug substance(s) on a representative sample of the batch
using an appropriate analytical method. This value is expressed as percentage
of label claim and assumes that the concentration (weight of drug substance per
weight of dosage unit) is uniform. Then accurately 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 acceptance value as weight variation for uniformity of
dosage unit determination.
10. Accurately
weigh 10 capsules individually, taking care to preserve the identity of each
capsule. Remove the contents of each capsule by a suitable means. Accurately
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 acceptance value as weight variation for uniformity of dosage unit
determination.
11. Acceptance
value for content uniformity (AV) = (98.5 –
+ks)
12. Acceptability
constant: If n = 10, then k =2.4; If n = 30, then k =2.0
13. Maximum
allowed acceptance valueL1 is 15.0 and L2 is 25.0.
14. The
requirements for dosage uniformity are met if the acceptance value of the first 10 dosage
units is less than or equal to L1%. If the acceptance value is > L1%, test
the next 20 units, and calculate the acceptance value. The requirements are met
if the final acceptance value of the 30 dosage units is ≤ L1%, and no
individual content of any dosage unit is less than [1 − (0.01)(L2)]M nor more
than [1 + (0.01)(L2)]M as specified
in the Calculation of Acceptance Value under Content Uniformity or under Weight
Variation.
15. If
appropriate, these tests may be performed in-process; the acceptance criteria
should be included in the specification.
When weight variation is applied for new drug products exceeding the
threshold value to allow testing uniformity by weight variation, applicants
should verify during drug development that the homogeneity of the product is
adequate.
References:
- USP-NF {905}
- ICH Q6A
