Abstract
INTRODUCTION. Carvedilol is a drug used to treat renovascular hypertension and cardiovascular diseases. A monograph for carvedilol drug substance has been included in the State Pharmacopeia of the Russian Federation (SP RF); however, quality requirements lack for carvedilol products. In order to develop a relevant monograph, it appears feasible to systematize current Russian and global compendial requirements for carvedilol products.AIM. This study aimed to develop an approach to quality control of carvedilol medicinal products (tablets) and carvedilol drug substance.DISCUSSION. According to Russian State register of medicines, carvedilol drug substance by seven manufacturers and 18 authorized products in the form of tablets (of them, 11 authorized in the EAEU) are marketed in the Russian Federation. Carvedilol drug substance is included in SP RF, ed. XV, as well as the leading world pharmacopeias — European Pharmacopoeia (Ph. Eur.), British Pharmacopoeia (ВР), US Pharmacopeia (USP), Indian Pharmacopoeia (IP), Chinese Pharmacopoeia (ChP), Japanese Pharmacopoeia (JP), and Korean Pharmacopoeia (КР). Monographs for carvedilol tablets were included in several leading pharmacopeias — ВР, USP, IP, ChP, JP; ChP included a monograph for carvedilol capsules. The requirements were compared for key quality parameters: Identification, Related impurities, and Assay for the substance and the tablets; and Dissolution (additionally) for tablets. Standardization approaches to impurities and Dissolution test differ significantly between the pharmacopeias; basic methods to control impurities typically include high-performance liquid chromatography (HPLC); infrared spectroscopy is the basic identification method.CONCLUSIONS. A uniform approach has been suggested based on a comparative analysis of compendial documents. The approach helps to define quality requirements for carvedilol (drug substance and tablets): choosing high-priority parameters; providing a rationale for analytical methods (infrared spectroscopy, HPLC, titrimetry/HPLC assay, and dissolution); and setting standard requirements for risk-based control of impurities. The suggested approach is applicable for expert evaluation of carvedilol dossier and monograph draft for SP RF.