Virtual screening, synthesis, solid state characterization, evaluation for solubility, dissolution, and stability of gallic acid-based cocrystals of glimepiride

Glimepiride is a second generation Sulfonylurea class of antidiabetic drug. It belongs to BCS Class-II with a varying dissolution profile and bioavailability on account of limited aqueous solubility. The present study aimed to alter and improve physicochemical properties of glimepiride by modifying its crystal lattice through co-processing the same with an inert carrier like gallic acid to form cocrystals.

The present study deals with rational approach to select coformer for Co-crystallization of Glimepiride, followed by its confirmation by solid state characterization using FTIR, DSC and PXRD studies. Cocrystal formation and its effect on solubility, in-vitro drug release and stability were also evaluated.

Gallic acid was selected as coformer through multiple virtual screening methods such as COSMO-RS, Hansen solubility parameter (HSP), and pKa method. Cocrystal was formulated by solvent assisted grinding method using methanol and characterized by Fourier-transform spectroscopy (FTIR), Differential scanning calorimetry (DSC), Powder X-ray diffraction method (PXRD), and Solid state nuclear magnetic resonance spectroscopy (ssNMR) to identify the solid-state modification. Equilibrium solubility and in-vitro dissolution study were accomplished to estimate the solubility and dissolution behavior of cocrystals in comparison to pure drug. The drug content analysis of cocrystal formulation proved no loss of API during processing while stability study showed the integrity of drug in formulation throughout the study.

Cocrystal formation of Glimepiride with gallic acid was confirmed by spectroscopic changes in FTIR and DSC. Comparative PXRD and ssNMR study further endorsed the formation of new crystalline species. Experimental confirmation of cocrystals have proved reliability of virtual screening methods. The seven-fold rise in aqueous solubility of cocrystal formulation than that of pure drug attributed to new crystalline phase with minimum lattice energy that further contributed to drug solubility and dissolution enhancement.

Co-crystallization of Glimepiride with gallic acid is simple, reliable formulation approach to alter solubility and dissolution by altering crystal lattice of drug. Thus, co-crystallization is effective method for optimizing therapeutic efficacy of Glimepiride.