Improvement of Gliclazide Dissolution Rate Using In Situ Micronization Technique

Gliclazide (GLZ) is a second-generation sulphonylurea, widely used for the treatment of non-insulin dependent diabetes mellitus. However, due to its low solubility in water (55 mg/L) and gastric fluids, its bioavailability varied inter-individual. This research aims to enhance the dissolution rate of gliclazide using in situ micronization technique. The in situ micronization process was carried out using solvent change method by using hydroxypropyl methylcellulose E15 (HPMC E15) or tween 80 as stabilizing agents. The solution of 0.5 g or 1 g of gliclazide in 30 ml of dimethyl sulfoxide was mixed with the solution containing 0,05 g or 0,1 g of HPMC E15 or tween 80 in 100 ml of water under stirring at 1200 rpm in ice bath (about 5°C) for 30 minutes. Obtained suspensions were filtered through 0,45

μ

m cellulose acetate membrane. The dissolution test, scanning electron microscopy, particle size analysis, Fourier transform infrared spectroscopy (FTIR) and thermal analysis (DSC) were carried out to investigate the properties of the micronized gliclazide obtained. The in situ micronization technique used in this research enhanced the water-solubility and dissolution rate of gliclazide. The crystalline shape of GLZ changed from rod-shape or cube-shape to spherical shape with smaller size.