Enhancement of Glimepiride Bioavailability by Co-Crystallization Technique

Abstract

Abstract: Drugs with low aqueous solubility show limited oral bioavaibility and dissolution enhancement is a promising strategy for improving drug bioavailability. Co-crystallization is a promising technique used to improve the oral solubility and dissolution rate of the drugs and hence their oral bioavailability. In general pharmaceutical co-crystals improve the physical properties such as crystallinity, solubility, wettability and dissolution behaviors of the drug without altering its pharmacological activity. The aim of this study was to enhance the solubility, dissolution rate and limited oral bioavailability of glimepiride (GLM) by cocrystallization with different carboxylic acid co-formers. Different co-crystal formulations were successfully prepared by ultrasound assisted suspension co-crystallization technique and then suspected to solubility study to choose the best formula to complete the study. Co-crystal of glimepiride -oxalic acid was characterized by X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and then further evaluated for dissolution behavior. The result showed that co-crystal could increase solubility and dissolution rate of glimepiride. The results of XRPD, FTIR and DSC indicating the presence of a new crystalline phase and formation of cocrystal while the SEM micrograph revealed the definite shape with crystalline composition of co-crystal. In vivo bioavailability study in rats showed higher Cmax , longer t1/2 el and MRT0-∞ and increased AUC0-∞ of 2.66 fold compared to the plain GLM. Therefore, co-crystallization technique can be expected to represent a promising tool for enhanced delivery of glimepiride.