Polymorphism control of active pharmaceutical ingredients

Abstract

Рolymorphism is receiving increasing attention due to its influence on the physicochemical and pharmacological properties of the active pharmaceutical ingredients (API) while maintaining the molecular structure. This review is devoted to the problem of APIs phase state control both at the development stage and during the circulation of the drug. The term «polymorphism» has different definitions depending on the branch of science. There is no unambiguous solution to this issue in the regulatory documentation of pharmaceutical industry either. Based on the analysis of literary sources, the article presents a comparison of pharmacopeia methods, recommended in Russian and foreign regulatory documents for the analysis of polymorphism of medicinal substances, including state pharmacopeias of Russia, Belarus, Kazakhstan, the USA, and Japan, as well as international pharmacopeias of the European Economic Union and the Eurasian Economic Union. The trend on using a complex of high-tech equipment is revealed. A systematic approach to analysis based on X-ray diffraction, thermal, spectral, microscopic, biological, and physical methods for determining constants makes it possible not only to identify the polymorphic modification of API, but also to characterize its structure, morphology, physicochemical properties and pharmacological activity. In the Russian Federation, the phenomenon of polymorphism is being studied especially intensively, and some control methods, such as biological methods, are validated only in Russian pharmacopeia. A promising direction for further research is the improvement and harmonization of regulatory documentation within the framework of this chemical and technological field of pharmacy. A global approach will help to reduce not only the probability of poor-quality products entering the market, but also the costs of establishing the authenticity of the active pharmaceutical ingredient produced.