Gliclazide: Biopharmaceutics Characteristics to Discuss the Biowaiver of Immediate and Extended Release Tablets

Featured Application In line with the principles of the Pan American Health Organization and the World Health Organization (WHO), which permeates the development of technical cooperation, with a focus on producing timely evidence for health decision-making, our research group has contributed, for over a decade, with the production and analyses of information related to the biowaiver of medicines and with the related public policies. In this article, biopharmaceutics information about gliclazide was compiled and evaluated carefully, as it is the only oral antidiabetic agent indicated concomitantly as essential therapy by the WHO and Brazil, as well as a potential candidate for biowaiver according to the International Pharmaceutical Federation (FIP). Our results help close the gap in the literature on the biopharmaceutics classification by the Biopharmaceutics Classification System (BCS) and brings light to the possibility of biowaiver for new medicines containing gliclazide. Therefore, it also contributes to the aspirations of the WHO and the FIP. The lists of essential medicines of the World Health Organization (WHO) and Brazil include gliclazide as an alternative to the oral antidiabetic drug of first choice, metformin, in the treatment of type 2 diabetes mellitus because of its pharmacokinetic profile and few side effects. Thus, it is also considered by WHO and the International Pharmaceutical Federation (FIP) as a drug candidate to biowaiver, which is the evaluation of how favorable the biopharmaceutics characteristics are in order to obtain waiver from the relative bioavailability/bioequivalence (RB/BE) studies to register new medicines. This paper presents a review about the solubility, permeability and dissolution of gliclazide. A critical analysis of the information allowed to identify gliclazide as a Biopharmaceutics Classification System (BCS) Class II drug. Therefore, new drugs in immediate release dosage forms will not be eligible for biowaiver. Regarding the extended release dosage forms, besides the limited solubility, no information on the comparative dissolution profile was found, which would be necessary to analyze a possible biowaiver for a smaller dosage. It can be concluded that the registration of new medicines containing gliclazide must undergo RB/BE studies, since there is not enough evidence to recommend the replacement and waiver of such studies for immediate and extended release formulations.