In Vivo and In Vitro Evaluation of a Solid Dispersion System of Gliclazide:PEG 6000

Abstract

Objective: Gliclazide is a potent antidiabetic agent because of its capability to decrease blood glucose level via stimulating endogenous insulin secretion from beta-pancreas cells. Gliclazide is insoluble in water and has low dissolution rate. In this study, polyethylene glycol (PEG) 6000 was used as a matrix to disperse gliclazide in the solid state, and the pharmacokinetic profile of this solid dispersion was studied in rats. Design: The solid dispersion of Gliclazide:PEG 6000 (1:4) was prepared by solvent evaporation method. Main outcome measures: Samples characterization included differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray diffraction (XRD), and solubility and dissolution test. In vivo study was carried out in healthy rats, randomly. After a single dose of oral administration, blood samples were collected pre-dose (15 min before) and 1, 2, 3, 4, 5, 6, 8, 10, and 12 h post-dose. Plasma concentration of gliclazide was determined by high pressure liquid chromatography method using C-18 column, with mobile phase KH₂PO₄ (pH 4.6)–acetonitril (40:60 v/v) and UV detection at 229 nm. Results: Results showed that there were no differences in DSC, IR spectroscopy, XRD, and dissolution test between the solid dispersion and physical mixture. In vivo data showed that the T_max of gliclazide in solid dispersion and physical mixture was significantly decreased, while the C_max, AUC_0–12, and AUC_0–μ were significantly increased compared to gliclazide alone. These results indicate that the rapid T_max was due to rapid absorption of gliclazid across the GI tract membrane. Increased C_max, AUC_0–12, and AUC_0–μ indicate a better absorption of gliclazide in solid dispersion and physical mixture than of gliclazide alone. Conclusion: Increased in gliclazide dissolution in the presence of PEG 6000 was followed by improved in vivo data.