Abstract
INTRODUCTION.
Beta-blockers are one of the major groups of medicines used to treat cardiovascular diseases. Bisoprolol fumarate is of particular interest as it shows high selectivity towards beta-1 receptors. A monograph on bisoprolol fumarate drug substance was included in the State Pharmacopoeia of the Russian Federation, Edition XV (SP RF); however, there is no monograph on the medicinal product. Thus, it seems advisable to systematize the data on Russian and other national compendial requirements for bisoprolol fumarate medicinal product and drug substance.
AIM.
This study aimed to systematize quality requirements for drug substances in order to develop the guidelines on specification drafting for bisoprolol fumarate drug substance and bisoprolol fumarate tablets.
MATERIALS AND METHODS.
The study used a comparative analysis and a content analysis. The study object included the monographs of SP RF, European Pharmacopoeia (Ph. Eur.), British Pharmacopoeia (ВР), United State Pharmacopeia (USP), Pharmacopoeia of the Peoples’ Republic of China (ChP), Japanese Pharmacopoeia (JP), Korean Pharmacopoeia (KP), and Indian Pharmacopoeia (IP) for the quality of bisoprolol fumarate drug substance.
RESULTS.
Monographs for bisoprolol fumarate drug substance were included in SP RF, Ph. Eur., USP, IP, ChP, JP, and KP. There was no quality specification for bisoprolol fumarate tablets in SP RF; however, the monographs for this dosage form were included in BP, USP, ChP, and JP. The monograph Bisoprolol fumarate (SP RF) was compared to other pharmacopoeias; it is generally harmonized with Ph. Eur.; however, the monographs differed with regard to authentication of the active substance and the need to control fumaric acid content. Registration dossiers were analyzed for bisoprolol fumarate drug substances and tablets. It was concluded that combinations of high-performance liquid chromatography-thin-layer chromatography or high-performance liquid chromatography-spectrophotometry can be used to assess the quality of bisoprolol fumarate and identify the active substance.
CONCLUSIONS.
The performed study has justified the choice of quality parameters and analytical methods used to develop the guidelines on preparing specifications for bisoprolol fumarate tablets. The identified impurities can be described as process-related impurities resulting from the synthesis of the drug substance or degradation impurities; this is also applicable for the guidelines on specification drafting.