Physicochemical and Dissolution Enhancement of Ketoconazole via Succinic Acid-Based Solid Dispersion Systems

Ketoconazole is a poorly water-soluble antifungal drug, and its limited solubility restricts therapeutic performance. This study investigated the use of succinic acid-based solid dispersions, prepared by ball milling, to enhance their solubility and dissolution. The formulations were comprehensively characterized by polarized light microscopy, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and solubility and dissolution testing at pH 1.2 and 6.8. The results confirmed the transformation of ketoconazole from its crystalline form to a co-amorphous system, as evidenced by the absence of birefringence, disappearance of melting endotherms, the presence of a single glass transition temperature, and FTIR spectral shifts indicating drug–acid interactions. These structural modifications significantly improved drug solubility and dissolution behavior. The solid dispersions demonstrated nearly two-fold higher solubility and faster release than crystalline ketoconazole, sustaining supersaturation across acidic and neutral media. Overall, ball milling with succinic acid provides a simple, scalable approach to stabilize amorphous ketoconazole and enhance its biopharmaceutical properties.