The applications of the content uniformity test and the weight variation test on process validation tests of multiple ingredient preparations

Abstract

The new criteria for the weight variation test and the content uniformity test in general tests were revised in the Japanese Pharmacopoeia thirteenth edition (JPXIII), and both tests are used to determine the uniformity of dosage units. The weight variation test, if the content of an ingredient could be directed in the assay reported in JP13, replaces the content uniformity test. Although over-the-counter (OTC) drugs, for example medicine for coughs, are guaranteed to content uniformity, the applications of these tests have not been thoroughly investigated. We investigated whether one of the effective ingredients could be used as an indicator for the content uniformity of an OTC drug. The indicator was chosen by reason of the very small quantity compared to the others such as anhydrous caffeine in the case of cough medicine. When the mixing process was incomplete and the weight variation test was passed, the content uniformity of anhydrous caffeine in tablet varied in relative standard deviation and could not be guaranteed by this test, though both tests were passed as to the other ingredients. One ingredient such as anhydrous caffeine could not be used as a representative indicator for the other ingredients to confirm the content uniformity. And the content uniformity test could not be replaced by the weight variation test when the content uniformity of the mixed powder had not been confirmed. To guarantee the content uniformities of all effective ingredients of OTC drugs, the content uniformities in the mixing process should be confirmed respectively.