Abstract

This study aimed to improve the dissolution profile of two poorly soluble drugs, atorvastatin calcium and fenofibrate, through cocrystallization via carefully selected coformers. Five different coformers were screened via a molecular docking approach with the PyRx virtual screening tool. Binding energy and hydrogen bond formation data identified para-aminobenzoic acid (PABA) as the most suitable coformer for cocrystal formation. The cocrystallization process was carried out via the liquid-assisted grinding method. The resulting cocrystals were characterized via Fourier transform infrared (FT-IR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and scanning electron microscope (SEM) techniques. A detailed evaluation of fenofibrate, atorvastatin calcium, and fenofibrate−atorvastatin calcium-PABA multidrug cocrystals revealed improved solubility compared with that of the pure drugs. Characterization through FT-IR confirmed interactions between the drugs and the coformer, whereas PXRD, DSC, and SEM analyses supported the formation of a distinct crystalline phase. An in vitro dissolution study demonstrated a significant increase in the dissolution rate of the cocrystals. The findings concluded that cocrystals prepared with PABA via the liquid-assisted grinding method successfully improved the solubility of atorvastatin calcium and fenofibrate, providing a promising approach to address the challenges associated with poorly soluble drugs. The novelty lies in the strategic combination of two lipid-lowering agents into a single multicomponent crystal system, offering improved solubility, dissolution rate, and potential bioavailability compared to their standalone forms. This work pioneers the application of pharmaceutical cocrystallization for dual-drug delivery in dyslipidemia management, offering a promising platform for fixed-dose combination therapies with enhanced patient compliance and therapeutic synergy.

Key words: Novel Drug Delivery, Cocrystallization, Coformer, Fenofibrate, Atorvastatin Calcium.