Abstract
INTRODUCTION.
Metoclopramide is a medicinal product widely used as an antiemetic. The pharmaceutical industry applies metoclopramide in the form of base or hydrochloride monohydrate. The pharmacopoeial monograph for metoclopramide hydrochloride monohydrate drug substance was included in the State Pharmacopoeia of the Russian Federation (SP RF); however, SP RF specifies no quality requirements for metoclopramide-based medicinal products. In order to develop a relevant monograph, it seems necessary to systematize the current foreign and Russian compendial requirements.
AIM.
This study aimed to develop an approach to quality control of metoclopramide drug substance (hydrochloride and base) and a medicinal product in the dosage form of tablets.
MATERIALS AND METHODS.
The study used comparative data analysis and contentanalysis. Compendial requirements of SP RF, Edition XV, and the leading foreign pharmacopoeias — European Pharmacopoeia (Ph. Eur.), British Pharmacopoeia (BP), United States Pharmacopeia (USP), Indian Pharmacopoeia (IP), Pharmacopoeia of the People's Republic of China (ChP), Japanese Pharmacopoeia (JP), and Korean Pharmacopoeia (KR) were analyzed.
RESULTS.
We substantiated the choice of quality parameters, analytical methods and acceptability criteria used to draft the guidelines on preparing specifications for metoclopramide hydrochloride and base, as well as tablets. The requirements found in SP RF and foreign pharmacopeias were compared, as well as sections of registration dossier for drug substance and tablets covering key quality indicators: Identification, Impurities, and Assay for the substance and tablets; Dissolution (additionally for tablets). Recommendations were given to include quality parameters and analytical methods for the monograph on metoclopramide base. It was proposed to reduce the number of identification methods included in the monograph on Metoclopramide hydrochloride monohydrate.
CONCLUSIONS.
Сomparative analysis of compendial requirements has made it possible to offer a unified approach to the formation of quality requirements for metoclopramide products (drug substances and tablets). The approach of the British Pharmacopoeia is recommended for rationing any single impurity and total impurities. It is also recommended to include Metoclopramide base monograph in the SP RF.