Evaluation of the Discrepancy between the European Pharmacopoeia Test and an Adopted United States Pharmacopoeia Test Regarding the Weight Uniformity of Scored Tablet Halves: Is Harmonization Required?

Abstract

The aim of this study was to evaluate whether there exists any discrepancy between the European Pharmacopoeia (Ph. Eur.) and adopted United States Pharmacopeia (USP) tests concerning the weight uniformity measurements of tablet halves after splitting. The USP method does not contain provisions to evaluate split tablets, so here we adopt their whole tablet weight uniformity method. Twenty-nine different commercial scored tablets (local and imported) were divided. The split units were individually weighed and the relative standard deviation (RSD) for each product was calculated and then evaluated according to both the adopted USP and the Ph. Eur. tests of weight uniformity. Twenty out of the 29 products tested failed the USP test, while 14 of them failed the Ph. Eur. test. Nine products passed both the USP and Ph. Eur. tests. Six products passed the Ph. Eur. test but failed the USP test, with all of these products having an RSD greater than 6%. The correlation coefficient between the weight and content of split halves for three randomly selected products-corotenol 100 mg, corotenol 50 mg, and lorazepam 2.5 mg-was found to be 0.986, 0.998, and 0.72, respectively. A clear difference can be seen between outcomes obtained by the two compendial tablet splitting methods with regard to weight uniformity. Results from the USP test showed that tighter measures are needed to pass the test. Our results argue that the Ph. Eur. should revise the existing weight uniformity test on scored tablets to include the RSD parameter in it. The USP should include this adopted test as a specific test for scored tablet halves, not just whole tablets. Manufacturers in some cases will need to improve the quality of the produced scored tablets in order to pass the USP test, especially those with low therapeutic indices. Finally, harmonization between the pharmacopoeias regarding the weight uniformity testing of split tablets is warranted.

Lay abstract: The aim of this study was to evaluate whether there exists any difference between the European Pharmacopoeia (Ph. Eur.) and adopted United States Pharmacopeia (USP) methods to evaluate weight uniformity when drug tablets are split. The USP method does not contain provisions to evaluate split tablets, so here we adopt their whole tablet weight uniformity method. Twenty-nine different commercial scored tablets were obtained and divided. The split units were individually weighed and the relative standard deviation (RSD) of the split tablets for each product was calculated and then evaluated according to both methods. Twenty out of the 29 products tested failed the USP method, while 14 of them failed the Ph. Eur. method. Six products passed the Ph. Eur. test but failed the USP test because these products had an RSD greater than 6%. A clear difference can be seen between the pass/fail results of tablet splitting obtained by the two methods. The USP test showed that tighter measures are needed for products to pass the test. We recommend that the Ph. Eur. include the RSD parameter in it to make the method more rigorous. The USP is also recommended to include this adopted test as a specific test for scored tablet halves, not just for whole tablets. In the cases where the tablets failed either test, manufacturers should improve the quality of the produced scored tablets. Finally, using the same weight uniformity method by all pharmacopoeias is recommended.