Strategic LAG- Assisted Co-Crystal Engineering of Glimepiride with Central Composite Design-Guided Optimisation

Glimepiride, a second-generation sulfonylurea, is commonly prescribed for the management of type 2 diabetes mellitus, but its therapeutic application is restricted by poor aqueous solubility, leading to limited oral bioavailability. To overcome this drawback, the present study aimed to enhance the solubility of glimepiride through the development of pharmaceutical co-crystals with ascorbic acid, a Generally Recognized as Safe (GRAS) co-former. Co-crystals were prepared using the solvent drop grinding method, a green and efficient technique that promotes molecular interactions without excessive solvent consumption. The synthesized co-crystals were characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). These techniques confirmed the formation of a novel crystalline phase, distinct from the parent compounds, with no evidence of chemical incompatibility. In vitro dissolution studies demonstrated a significant improvement in aqueous solubility and dissolution rate of the co-crystals compared to pure glimepiride. The enhancements are attributed to alterations in the crystal lattice and improved wettability, resulting in superior drug release behaviour. Furthermore, the co-crystal formation process was systematically optimized using Design Expert software employing a central composite design approach to identify the best formulation conditions. Overall, this study highlights co-crystallization as a promising and scalable strategy for improving solubility-limited bioavailability of BCS Class II drugs like glimepiride, offering potential for more effective oral antidiabetic therapies.