Compatibility of Medicinal and Excipient Substances in the Development of Medicinal Formulations

Аннотация

Attention is drawn to a contradiction associated with assessments of the compatibility of medicinal (MS) and excipient (ES) substances: that ES and MS able to react with each other chemically are regarded as incompatible, yet at the same time, the compositions of several original medicines include ES and MS which are able to undergo chemical interactions. To remove this contradiction, the concept of “potential incompatibility” of ES and MS is introduced, i.e., the ability of substances to undergo direct or indirect chemical or undesirable physical interactions which may potentially become apparent during the manufacture or storage of a medicinal formulation and influence its quality. It is emphasized that incompatibility between an ES and an MS can be regarded as existing only when it is not possible to ensure their compatibility in a medicinal formulation. Approaches to assessing the compatibility between ES and MS are discussed: stress experiments using chromatographic analysis methods; stress experiments using spectral analysis methods; experiments using thermal analysis methods and calorimetry. A systematic “step-by-step” approach to studying the compatibility between ES and MS is proposed, based on express testing of the interaction between ES and MS not only in model mixtures, but also in samples of the medicinal formulation under development. This has decisive value for drawing reliable conclusions regarding the compatibility between the ES and the MS. Known types of potentially incompatible substance important for predicting potential incompatibility between ES and MS based on the structural characteristics and chemical properties of the molecules are presented. Recommendations are made in relation to studies of the compatibility of ES and MS.