Background: Glimepiride has limited aqueous solubility and majorly suffers from bioavailability issues that eventually reduce the pharmacotherapeutic potentials of the moiety. Materials and Methods: For the possible augmentation of all the crucial factors, co-crystals were developed using a Generally Recognized As Safe (GRAS) co-former (caffeine) in the presence of few drops of solvent (acetone) by employing a very simple green approach (solvent drop grinding method). The pharmacokinetic study of the cocrystals was performed in Wistar albino rats, the data was compared with free drug form and pharmacokinetic parameters were determined. The fabricated co-crystal product was comprehensively characterized through sophisticated analytical techniques that ascertained the complete product formation. Results: The formation of the glimepiride crystal with the co-former was confirmed through FTIR, DSC, XRD and SEM. From the pharmacokinetic study in rats, the procured data expressed several-folds higher plasma drug concentration which can be correlated with increased bioavailability of glimepiride. Conclusion: This study will positively inspire researchers working in the field of solubility/ bioavailability enhancement due to the simplicity of the method, green approach and positive results which will open several future avenues of drug applications.

The pharmaceutical cocrystals and its engineering is widely accepted phenomenon regarding to the enhancement of aqueous solubility of poorly soluble drugs. The pharmaceutical cocrystals have the great ability to improve the physicochemical properties of drug substance. Cocrystals are formed by the stoichiometric combination of drug substance and the coformer. The drug glimepiride is a third generation oral hypoglycemic sulfonylurea class. Glimepiride is a drug which is get classified as biopharmaceutical classification system (BCS) class II which indicates the glimepiride having low aqueous solubility and high permeability. Cocrystal engineering is a perfect way to increases glimepiride solubility without changing its therapeutic property. The cocrystals were synthesized by the solvent drop grinding as a green chemistry approach. The coformers used to form the cocrystals are succinic acid (SA), Theobromine (TB), caffeine (CF). The synthesized cocrystals are get characterized by vibrational spectroscopy, thermal analysis, molecular crystallography, and optical microscopy. The obtained results shows the formation of cocrystal phase between the drug glimepiride and its coformers.