ABSTRACT:
Flurbiprofen (FLU) is a nonsteroidal anti-inflammatory drug (NSAID) that falls under the Biopharmaceutics Classification System (BCS) Class II, which indicates low aqueous solubility and high permeability. Due to its limited solubility, the oral bioavailability of FLU is significantly reduced, posing a challenge to its therapeutic effectiveness. Therefore, several formulation strategies have been explored to enhance its solubility and absorption. Among these, co-crystallization has recently emerged as a promising approach. In the current study, three co-formers—Adipic acid (ADP), Glutaric acid (GLU), and Nicotinamide (NCT)—were selected for co-crystal formation with FLU. The selection was guided by Hansen Solubility Parameters (HSP) and the acid–base complementarity rule. Co-crystals were prepared using both slow and rapid solvent evaporation techniques. Differential Scanning Calorimetry (DSC) analysis showed no evidence of new crystal phases for most combinations, except for FLU-NCT mixtures prepared by both evaporation methods. These findings were further confirmed by Powder X-ray Diffraction (PXRD) and Fourier-Transform Infrared Spectroscopy (FTIR), which provided strong evidence of co-crystal formation exclusively between FLU and NCT. Moreover, PXRD and DSC results indicated that the FLU-NCT co-crystals synthesized via rapid solvent evaporation were purer than those obtained through the slow evaporation method.