Enhancement of Solubility and Bioavailability of Glimepiride Using Solid Dispersion Technique

The poor aqueous solubility of Glimepiride is the major factor limiting its oral bioavailability.  The objective of the work is to enhance the solubility of Glimepiride, there by its bioavailability by using solid dispersion technique. Solid dispersions of Glimepiride were prepared by using Poly vinyl Pyrrolidone (PVP K30), by solvent evaporation method in different ratios of 1:0.5, 1:1, 1:3, 1:5 respectively and evaluated for its in vitro & in vivo release along with Mdsc & FTIR. The equilibrium solubility of solid dispersions was determined in water to study the effect of PVP K30 on solubility of Glimepiride. In Vitro dissolution studies were conducted in water from solid dispersions equivalent to 4 mg of Glimepiride. Protocol bound in vivo studies were conducted in non diabetic rats with the best formulation. Two groups of rats (6 rats in each group) were orally fed Glimepiride as plain drug dispersion (control group) & as drug: PVP K30 solid dispersion (test group). The fall in blood glucose level was monitored over 24 hours. Successful conversion of the crystalline Glimepiride to amorphous solid dispersion was achieved at 1:5 level of drug to PVP K30 (F4). The solid dispersion prepared with PVP K30 at 1:5 level (F4) showed a 4 folds enhancement in aqueous solubility of the drug. So the in vivo studies conducted with 1:5 drug to PVP K30 (F4) solid dispersion, the best formulation, it was observed that the fall in the test group is significantly faster and more intense as compared to the control group. The above study shows that solid dispersion of Glimepiride offers an simple and attractive solution to increase the solubility of the poorly water soluble drug and thereby improve its oral bioavailability. Key words: Glimepiride, Poly vinyl Pyrrolidone (PVP K30), Solid dispersions (SD)