Elaboração de um guia para registro do hipoglicemiante oral acarbose no Brasil

Abstract

Acarbose is a highly soluble substance with very low permeability and absorption and has local action on the gastrointestinal tract, so relative bioavailability studies are not appropriate to evaluate comparability between acarbose formulations. Thus, the possibility of performing pharmacodynamic tests to replace bioavailability studies or comparative dissolution profile studies is evaluated. Currently the registration of acarbose immediate-release tablets is regulated by the resolution of biological products and requires several costly in vivo studies. However, in March 2019 was published the public consultation 633/2019 on the regulation of registration of less complex biological products, which enables the registration of some drugs through comparability with a product already established in the pharmaceutical market. The new regulation establishes the presentation of comparative studies of pharmaceutical equivalence between products and relative bioavailability studies or technical justification for bioavailability. The purpose of this study is to propose a registration guide for acarbose immediate-release tablets that will indicate the most appropriate tests for comparability studies. FDA agency has published a guidance document entitled “Guidance on Acarbose tablets” which deals with a registration guide for the acarbose immediate release tablet product, which sets out two types of tests to assess the bioequivalence of acarbose formulations: a profiling test. of dissolution and a pharmacodynamic study.A critical analysis of the model proposed by the FDA guide is performed through a discussion of a published article concerning a pharmacodynamic bioequivalence study of acarbose immediate release tablet formulations prepared in the format that establishes the FDA acarbose tablet registration Guidance. The FDA acarbose guide establishes the use of serum glucose concentrations as a pharmacodynamic outcome. The results of the article point out that pharmacodynamic bioequivalence studies to evaluate comparability between acarbose products suffer great interference from the homeostatic glucose control mechanisms, becoming less robust. Consequently, dissolution profile studies become the most suitable alternative to evaluate the comparability between two acarbose products, as the main variables to be monitored are the solubility and dissolution of the formulation and the biochemical variables of the living system do not interfere with the comparability methods. At the end, the registration guidance for the medicine acarbose immediate release tablets is presented.