Optimization, in-vitro Release and in-vivo Evaluation of Gliquidone Nanoparticles.

Abstract

The present work embarks upon increasing the dissolution rate and the bioavailability of model anti-diabetic drug, gliquidone, a sulfonylurea class drug used for treating diabetes mellitus type 2. The gliquidone nanoparticles were prepared by using anti-solvent precipitation technique in which, gliquidone solution in acetone was added at a controlled rate to an aqueous solution containing polyvinylpyrrolidone K25 (PVP K25) as stabilizer. The effect of drug concentration (X1), polymer concentration (X2) and solvent to anti-solvent ratio (X3) on particle size and dissolution was studied using Box-Behnken design. The results revealed that by decreasing the drug concentration and by increasing the stabilizer concentration and solvent/anti-solvent ratio, reduction in the size of the particles was observed. The mentioned parameters were optimised and particle of size about 175 nm was achieved. The relative dissolution rate of prepared gliquidone nanoparticles in phosphate buffer pH 7.4 was ~ 4.7 times faster than original drug at t = 45 min. Further, the gliquidone nanoparticles were characterized by scanning electron microscope (SEM), Fourier transform-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). The particles revealed to be oval in shape with stabilizer molecules on surface and exhibited decreased crystalline nature when compared to free gliquidone. Finally, the in vivo studies using gliquidone nanoparticles revealed ~ 2.5-fold increase in Cmax when taken orally in the form of hard gelatin capsules in comparison to free gliquidone. Thus, overall investigation suggests that the developed strategy of gliquidone nanoparticles possess a keen potential for exhibiting anti-diabetic effect.