Pharmaceutical Co-crystal of Ketoconazole-adipic Acid: Excipient Compatibility and In Silico Antifungal Potential Studies
Abstract
OBJECTIVE: This research aimed to investigate the compatibility of the Ketoconazole-Adipic Acid (KTZ-AA) co-crystal, which exhibits an improved dissolution profile over pure Ketoconazole, with various solid pharmaceutical excipients, as well as its in silico antifungal potential. METHODS: Binary physical mixtures (1:1 w/w) of KTZ-AA co-crystal and excipients were analyzed using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD). The molecular docking study targeting the sterol 14α-demethylase (CYP51) enzyme of the pathogenic yeast Candida albicans was performed. RESULTS: DSC results indicated compatibility between co-crystal and six tested excipients: lactose monohydrate, polyvinylpyrrolidone K90, microcrystalline cellulose, corn starch, colloidal silicon dioxide, and talc. In the case of the co-crystal and magnesium stearate mixture, DSC revealed a change in the thermal behavior, suggesting the formation of a eutectic system. However, TGA demonstrated that the decomposition profile of the co-crystal remained unaffected in all binary mixtures. PXRD and FT-IR further confirmed the absence of chemical interactions between the co-crystal and all excipients under ambient conditions. Moreover, the KTZ-AA co-crystal maintained its chemical stability without degradation after three months storage under accelerated conditions (40°C/75% RH). The molecular docking study…
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Evidence Hub reads this as a simulation / modelling, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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