Dissolution enhancement of gliclazide using in situ micronization by solvent change method

Gliclazide (GL) is a second-generation sulphonylurea, widely used for the treatment of non-insulin dependent diabetes mellitus. The low water-solubility of GL leads to a low dissolution rate and variable bioavailability. The aim of this study was to enhance the dissolution rate of GL by the preparation of micron-sized particles using a solvent change method. The in situ micronization process was carried out using solvent change method in the presence of HPMC or Brij 35 (0.05 or 0.1 g) as stabilizing agents. GL (0.5 or 1 g) was dissolved in acetone and the stabilizing agent in water (as non-solvent). The non-solvent was poured rapidly into the drug solution under stirring at 26,000 rpm by an ultra-homogenizer, and the resultant was freeze-dried. The crystalline shape of GL changed from rod-shape to diamond- or cube-shape. The FTIR and DSC results showed no interaction between the drug and the stabilizers. Presence of sharp peaks in the XRD diffractograms of microcrystals with 10 times smaller height than untreated crystals indicates that a crystalline habit modification has occurred in the microcrystals without any polymorphic changes. The particle size was reduced about 50 times and the dissolution efficiency of GL at 15 min (DE15%) was increased about 4 times. © 2008 Elsevier B.V. All rights reserved.