Les Problèmes de Formulation lies aux Impuretés des Excipients

Abstract

Excipients are usually the main components of drug formulations, but new pharmaceutical forms and the use of increasingly active active ingredients mean that the ratio of excipients to active ingredients in the formulation is increasing. And even if the various pharmacopoeias take charge of the control of excipients and define specifications and acceptance criteria. The fact remains that knowledge of impurities in excipients is less than that available for active ingredients, due to the absence of DMF and/or CEP procedures for excipients. New sources of excipients arising from the globalization of the excipient trade carry the risk of new, poorly understood impurities linked to different production processes. Impurities in excipients pose two types of risk: ● The toxic risk. ● The risk of interaction with the active ingredient, which cannot always be predicted despite the compatibility studies carried out during pharmaceutical development. In our study we have taken two case study models, one dealing with the incompatibility of excipients and the other with the toxicity of excipients. We propose the use of excipients with known quantities of formaldehyde or other crosslinking agents, and controlled storage conditions or gelatin capsules protected from high humidity. And in view of the increased risk of toxicity from excipients, we suggest that the CPMP/SWP/5199/02 explanatory note on the genotoxic limit of impurities, although intended for genotoxic impurities in new active ingredients, should be applicable in its concept to excipients, in particular the notion of a "Toxicological Limit Concentration" with a maximum acceptable daily dose.