Development and characterization of glimepiride nanocrystal formulation and evaluation of its pharmacokinetic in rats

Abstract

In this paper, orally nanocrystal capsules were produced using nanocrystal formulations in order to optimize dissolution properties of poorly soluble drug glimepiride and improve its bioavailability. The important preparation variables, such as stabilizers, the power input and the time length of ultrasonication on the mean particle size and polydispersity index were investigated systematically, and the optimal values were 0.2% glimepiride (w/v), 1.2% Lipoid S100, 0.6% PEG 6000 (w/v), 0.6% PVPK 30 (w/v), 500 W and 2 min, respectively. Characterization of glimepiride nanocrystal was carried out by X-ray powder diffractometry, differential scanning calorimetry and scanning electron microscopy. In vitro dissolution test, the nanocrystal-loaded capsules of glimepiride showed an evident increase in dissolution rate compared to micronized and market capsules. The in vivo studies demonstrated that a marked enhancement of bioavailability of nanocrystal-loaded capsules was superior compared to the marketed formulation and microcrystal-loaded capsules, which may reduce the risk of side effect by allowing a reduction in either the dose or its frequency of administration. © 2013 Informa Healthcare USA, Inc.