Design, Synthesis, and Evaluation of Novel Pharmaceutical Co-crystals of an Antidiabetic Drug to Enhance Solubility and Biopharmaceutical Performance

Poor aqueous solubility and limited oral bioavailability continue to be major formulation challenges for several antidiabetic drugs, particularly those classified under Biopharmaceutical Classification System (BCS) Class II, where drug absorption is primarily limited by dissolution rate. Glimepiride, a widely prescribed sulfonylurea antidiabetic agent, belongs to BCS Class II and exhibits low water solubility despite high permeability, resulting in variable bioavailability and delayed therapeutic response. Addressing these limitations through solid-state modification is therefore of significant pharmaceutical interest. Pharmaceutical cocrystallization has emerged as an advanced crystal engineering strategy capable of tailoring the physicochemical and biopharmaceutical properties of active pharmaceutical ingredients without altering their chemical structure or pharmacological activity. In the present study, novel pharmaceutical co-crystals of glimepiride were designed, synthesized, and evaluated using pharmaceutically acceptable co-formers. Co-crystals were prepared in a fixed 1:1 molar ratio employing solvent drop grinding, co-grinding, and solvent evaporation techniques to explore both solid-state and solution-based assembly pathways. The prepared co-crystals were systematically characterized using Fourier Transform Infrared Spectroscopy (FTIR) to investigate intermolecular interactions, Differential Scanning Calorimetry (DSC) to assess thermal behavior and phase transitions, and Powder X-ray Diffraction (PXRD) to confirm the formation of new crystalline phases. Further evaluation included saturation solubility studies, micromeritic property assessment, and in-vitro dissolution studies to determine improvements in pharmaceutical performance. The optimized glimepiride co-crystals demonstrated a marked enhancement in aqueous solubility and dissolution rate compared to the pure drug, along with improved flow properties suitable for solid oral dosage form development. These improvements are particularly relevant for BCS Class II drugs, where enhanced dissolution directly translates to improved oral bioavailability. Overall, the findings confirm that pharmaceutical cocrystallization is an effective and promising approach for improving the biopharmaceutical performance of poorly soluble antidiabetic drugs and offers significant potential for the development of more efficient and patient-friendly oral solid dosage forms.