Analytical, biopharmaceutical and regulatory evaluation of topical testosterone preparations

Abstract

Testosterone-containing pharmaceutical products for topical use were obtained from the pharmacist or through the internet. The legal status of the different products obtained is discussed: some products through the internet were clearly a medicinal product according to the current definitions, while they are not registered as such. Assay and impurity profiles of each of the marketed samples were obtained using HPLC–UV and ESI-iontrap MS. The analytical results were evaluated relative to the reporting, identification and qualification thresholds as defined by the the International Conference on Harmonisation (ICH) and the European Pharmacopoeia (Ph. Eur.). Preparations with impurities above the qualification threshold were observed. Moreover, in vitro release profiles over an artificial membrane were obtained using a standardised cell in a paddle dissolution bath as well as in a static Franz diffusion cell, using phosphate buffered saline (PBS; pH 7.0) containing 5% bovine serum albumin (BSA) as dissolution or receptor fluid. This biopharmaceutical quality attribute differs significantly between the preparations tested. In conclusion, the equivalency of topical testosterone preparations is not assured, nor on their legal status, nor on their impurity profiling nor on their biopharmaceutical behaviour. This calls for an urgent trans-national product-class harmonisation approach.