Enhancement of Solubility of Antifungal Ketoconazole by Co-crystallization

Abstract

Ketoconazole is available in various oral and topical forms. It is a weak base and has limited solubility except in highly acidic conditions. It falls under Class II in the Biopharmaceutics Classification Scheme due to high permeability but low water solubility (0.087 mg/l at 25 °C). A cocrystal of ketoconazole was synthesized using the solvent crystallization method and characterized using FTIR spectroscopy, DSC, melting point, and solubility analysis. The FTIR spectrum indicated non-covalent interactions (hydrogen bonding) in the cocrystal, resulting in improved physical properties compared to the individual components. The melting point of the cocrystal was lower than that of the single API (146.0-148.0 °C), specifically (141.0-143.0 °C) and (115.0-119.0 °C) for suberic acid and sebacic acid cocrystals, respectively. The ketoconazole cocrystal exhibited enhanced solubility compared to pure ketoconazole. This study demonstrated the successful formation of co-crystals between ketoconazole and suberic acid, sebacic acid, and various co-solvents, leading to improved drug solubility.