Uniformity of dosage units--comparative study of methods and specifications between Eur. Pharm. 3rd and USP 23.

Methods and specifications of Eur. Ph. 3rd Ed. and USP 23 for the evaluation of the uniformity of dosage units were compared, in relation to: (i) allowed dispersion of the sample; and (ii) adequability to control the individual contents of active ingredient in relation to the labelled amount. Using the characteristics of the normal distribution curve, we calculate: (1) the highest dispersion allowable, represented by the relative standard deviation of the uniformity of mass of single-dose preparations of Eur. Ph. 3rd Ed., (results were 3.4, 5.1 and 6.8% for L1 = 5, L = 7.5 and L = 10, respectively); and (2) for all the methods studied the allowable units frequency for different intervals of the labelled amount. Differences between the tests of Eur. Ph. 3rd Ed. and USP 23 can lead to acceptance samples with very different individual contents variability, namely if the limit specifications for the strength was +/- 10%. The main reasons for that are: (1) in Eur. Ph. 3rd Ed., the limits are set with reference to the average content of the sample, and in USP 23, they are set with reference to the labelled amount of the active ingredient; and (2), the USP 23 calculates the content of active ingredient in each tablet from the result of the assay, when the weight variation method was used. Taking +/- 5% of label claim as the specification for the strength of the product, according EEC requirements, the maximum percentage of units outside the range 95-105% of label claim allowed by Eur. Ph. 3rd Ed. and USP 23 tests are similar.