An Approach for Improvement of the Water Solubility of Gliclazide in Solid Dispersion with Peg

Gliclazide is a second-generation hypoglycaemic sulfonylurea that is useful in the treatment of Type 2 diabetes mellitus. It shows low aqueous solubility and dissolution rate and often shows low and irregular bioavailability after oral administration. This paper describes an approach to improve the Solubility of gliclazide by using solid dispersions (SDs) in polyethylene glycol 4000 (PEG 4000). Solid dispersions were prepared by a solvent-melting method and Solubility determinations were performed in triplicate according to the method of Higuchi and Connors. The solubility of gliclazide is 0.86 mg/ml in water but after the addition of different concentration of PEG 4000, the solubility of gliclazide is increased maximum 3.07 mg/ml at 20%w/v of PEG 4000, was observed. The main conclusion of this article is that the solubility of gliclazide can be enhanced in Solid Dispersion with PEG 4000. The solubilization effect of PEG 4000, reduction of particle aggregation of the drug, absence of crystallinity, increased wettability and dispersibility, and alteration of surface properties of the drug particles may be responsible for the enhanced solubility of gliclazide from its Solid Dispersion. INTRODUCTION: Gliclazide is a second-generation hypoglycaemic sulfonylurea that is useful in the treatment of Type 2 diabetes mellitus . Gliclazide shows a low incidence of hypoglycaemia; a low rate of secondary failure inhibits platelet aggregation, good tolerability and increases fibrinolysis 2, . It shows low aqueous solubility and dissolution rate and often shows low and irregular bioavailability after oral administration. Thus gliclazide appears to be a drug of choice in long-term sulfonylurea therapy for the control of Type 2 diabetes mellitus . Solubility of Gliclazide in water is very poor, thus affected oral bioavailability of drug. One of the most challenging aspects of formulation development is the enhancement of oral bioavailability of poorly watersoluble gliclazide drug. The solid dispersion of poorly water-soluble drugs in water-soluble polymers enhances drug solubility and its bioavailability . The preparation and characterization of complexes of gliclazide with β-cyclodextrin , complexation of gliclazide with β-cyclodextrinhydroxypropyl methyl cellulose, which enhanced its hypoglycemic activity , accelerated absorption of gliclazide using PEG 400 , Solid dispersions of gliclazide in PEG 6000 have been developed to increase drug dissolution rate , Enhancement of the solubility of gliclazide using polyvinylpyrrolidone K90 12 have been reported. The molecular weight of the polymer may play a role in the performance of a solid dispersion. The rationale of the present study was to investigate the use of lower molecular weight PEG 4000 for the preparation of solid