Abstract
INTRODUCTION
. Loperamide hydrochloride medicinal products are registered in the Russian Federation in the dosage forms of “tablets” and “capsules”. Since the State Pharmacopoeia of the Russian Federation (SP RF) does not include pharmacopoeial articles on dosage forms of loperamide hydrochloride, it seems relevant to conduct a comparative analysis and summarize the requirements of foreign pharmacopoeias for quality control of medicinal products based on loperamide hydrochloride.
AIM.
Analysis and generalization of quality requirements for loperamide hydrochloride medicinal products for the preparation of recommendations for the compilation of specifications for drugs containing loperamide hydrochloride in tablet and capsule dosage forms, and recommendations for updating the current pharmacopoeial article for the pharmaceutical substance loperamide hydrochloride.
MATERIALS AND METHODS
. A study of the quality requirements to pharmaceutical substances of loperamide hydrochloride in the dosage forms of tablets and capsules has been conducted using SP RF, the European Pharmacopoeia (Ph. Eur.), the British Pharmacopoeia (BP), the United States Pharmacopoeia (USP), the Indian Pharmacopoeia (IP), the Pharmacopoeia of the People’s Republic of China (ChP), the Korean Pharmacopoeia (KP), and the International Pharmacopoeia (Ph. Int.). The materials of registration dossiers for loperamide hydrochloride have been reviewed.
RESULTS
. Loperamide hydrochloride is not described in the SP RF. The pharmacopoeial monograph for the pharmaceutical substance loperamide hydrochloride is included in the SP RF (15th ed.), as well as in Ph. Eur., BP, USP, IP, ChP, KP, and Ph. Int. A comparative analysis of pharmacopoeial quality standards for the pharmaceutical substance loperamide hydrochloride revealed that FS.2.1.0613 “Loperamide hydrochloride” of the SP RF is largely harmonized with Ph. Eur., its requirements are among the most stringent and employ more sophisticated methods for identifying and controlling impurities compared to USP, IP, ChP, and KP. However, when revising the pharmacopoeial articles, the combination of methods for identifying loperamide should be optimized, and the control of heavy metals by a semi-quantitative method should be excluded, replacing it with an assessment of the risks of elemental impurity content.
CONCLUSIONS
. In preparing specifications for loperamide tablets and capsules, recommendations were provided for the use of combinations of identification methods, potential differences in dissolution testing conditions and standards were identified, and specified impurities were defined. Using various modifications of loperamide as an example, areas for improving the standardization of tablets are demonstrated, including the need for both disintegration and dissolution testing. The feasibility of monitoring the dosage uniformity of lyophilized tablets, regardless of dosage, using the calculated mass method is substantiated.