The biowaiver of bioequivalence studies on class I drugs of the biopharmaceutics classification system (BCS) is aimed mainly at reducing the costs and the exposure of health volunteers to a new pharmaceutical formulation. Fluconazole is an important antifungal agent but in the literature it is not clear whether it belongs to BCS class I or III. Compatibility studies are considered to be the first step in product development and on considering a biowaiver candidate these gain even greater importance since the final product will not be submitted to in vivo tests. The aim of this study was to qualitatively determine the composition of a commercially available fluconazole formulation in the form of capsules with regard to the presence of critical excipients and to carry out compatibility studies by differential scanning calorimetry (DSC). One formulation did not contain sodium lauryl sulfate and contained mannitol, in contrast to the reference formulation, which could hinder the acceptance of the biowaiver. The interaction of fluconazole with microcrystalline cellulose and calcium hydrogen phosphate dihydrate was observed; however, no indication of incompatibility was found in the DSC analysis of the commercial pharmaceutical formulations. These interactions were also studied by Fourier transform infrared spectroscopy, where small changes in the bands were observed, and by X-ray Powder diffraction and scanning electron microscopy that did not evidence any modification in the solid state characteristics.
The aim of this work was to assess if the commercially available Fluconazole drug products (Reference, Generic and Similar) would meet the biowaiver criteria from Food and Drug Administration (FDA) and Brazilian Agency for Health Surveillance (ANVISA) agencies. All formulations were evaluated considering the dissolution profile carried out in Simulated Gastric Fluid (SGF) pH 1.2, Acetate Buffer (AB) pH 4.5 and Simulated Intestinal Fluid (SIF) pH 6.8. The results demonstrated that all formulations fulfilled the 85% of drug dissolved at 30 min criterion in SGF pH 1.2. However, in AB pH 4.5 and SIF pH 6.8, some formulations, including the comparator, did not achieve this dissolution percentage. The discrepant dissolution profiles also failed the ƒ2 similarity factor analysis, since none of the formulations showed values between 50 and 100 in the three dissolution media. Comparative dissolution profiles were not similar, considering that the main issues concerning the dissolution were evidenced for the comparator product. Hence, a revision in the regulatory norms in order to establish criteria to switch the comparator could result in an increased application of drugs based on biowaiver criteria.
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