Physicochemical characterization of gliclazide solid dispersions prepared by povidone, cross povidone and microcrystalline cellulose

Abstract

Gliclazide is a sulfonylurea hypoglycemic drug which is used in the treatment diabetes mellitus type 2. Gliclazide is practically insoluble in water. In order to improve the drug dissolution rate, co-grinding method was used to prepare gliclazide solid dispersions (SDs) containing carriers namely povidone (PVP-K30), cross-povidone and microcrystalline cellulose in different drug to carrier ratios. The dissolution rate of gliclazide from the SDs was measured by using USP dissolution apparatus II, respectively, at two physiological pH values of 1.2 and 7.2 simulating gastric and intestinal fluids. The dissolution rates of the formulations were dependent on the nature of carriers and ratio of drug to carriers in SDs and the corresponding physical mixtures as well as the pH of medium. The dissolution rate of gliclazide was faster at high pH than that of low pH. The fastest dissolution rates were observed from SDs with the drug to carrier ratio of 1:5. The amount of drug dissolved in 15 minutes from these SDs was varied from 96% in the case of avicel SD to 100% for SD of PVP at basic medium. Whereas the amount of drug released in the same time from pure drug powder, treated drug powder and all physical mixtures was between 60 and 80%. These results indicate that the dissolution rate is highly enhanced from the SDs. DSC as well as X-ray Diffraction showed that the drug crystallinity in SDs was reduced. Also scanning electron microscopy and particle size analysis of intact and treated gliclazide revealed a significant reduction in particle size of treated drug. Whereas FT-IR spectroscopy demonstrated no detectable interactions between the drug and carriers. In addition to later evidences, increased wettability and hydrophilicity of drug particles and deaggregation brought about by the carriers are the reasons for the enhanced drug dissolution from the SDs. One of the possible advantages of formulating an insoluble drug such as gliclazide into SDs is that if it is used in preparation of capsules or tablets of the drug, its dose might be reduced which is economically beneficial.