Optimization of Curcumin-Ascorbic Acid Cocrystal for Enhanced Solubility, Tablettability, and Oral Bioavailability: Structural, Functional, and Pharmacokinetic Insights.

Curcumin (CUR) exhibits broad therapeutic potential across multiple disease conditions. However, it's extremely low aqueous solubility, poor dissolution, and limited oral bioavailability constrain its clinical utility. Therefore, the present study aimed to address the aforesaid limitations through design, optimization, and evaluation of a pharmaceutical cocrystal of CUR with ascorbic acid (CUR-AA-C). Initially, in silico modelling was employed to predict drug-coformer interactions, followed by optimization of the CUR-AA stoichiometry using a solvent-evaporation technique. The resulting solid form was systematically characterized by spectral techniques to confirm cocrystal formation. Subsequent evaluations included solubility assessment, antioxidant activity testing, and tablettability studies. A Design of Experiments (DoE) approach was further utilized to optimize the tablet formulation, and the pharmacokinetic performance of the optimized cocrystal tablet was assessed through in vivo bioavailability studies. Spectroscopic techniques confirmed successful CUR-AA-C formation. It exhibited a significant enhancement in solubility (12-fold in SGF and 13-fold in SIF) compared to neat CUR, attributed to modifications in the crystal lattice structure induced by the coformer. Antioxidant assays demonstrated a two-fold improvement in activity. Tablettability evaluations revealed an increase in compressibility and mechanical strength, supporting the development of robust tablets. Furthermore, the DoE-optimized cocrystal tablet showed a 6.3-fold increase in oral bioavailability relative to unmodified CUR. Overall, the prepared cocrystal demonstrated potential to enhance solubility, dissolution, manufacturability, and bioavailability, thereby improving the clinical applicability of poorly soluble natural compounds.