Cogrinding as an approach to enhance dissolution rate of a poorly water-soluble drug (gliclazide)

Gliclazide is practically insoluble in water. In order to improve the drug dissolution rate, cogrinding method was used as an approach to prepare gliclazide coground/solid dispersions (SDs) in the carriers such as povidone (PVP-K30), crospovidone and microcrystalline cellulose (Avicel PH 101) with different drug to carrier ratios. The dissolution rate of gliclazide from the SDs was measured at two physiological pH values of 1.2 and 7.2 simulating gastric and intestinal fluids using USP dissolution apparatus II. The concentration of the dissolved drug in the medium was determined by direct or first-derivative UV spectroscopy. The dissolution rates of the formulations were dependent on the nature and ratio of drug to carriers in SDs and the corresponding physical mixtures as well as the pH of the medium. At a higher pH the drug has a faster dissolution than at a lower pH. The fastest dissolution rates were observed from coground formulations with the drug to carrier ratio of 1:5. The amount of drug dissolved in 15 min from these SDs was varied from 96% in the case of Avicel SD to 100% for SD of PVP. Whereas the amount of drug released in the same time from unground drug powder (UD), ground drug powder (GD) 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 reduced drug crystallinity in SDs. Scanning electron microscopy and particle size analysis revealed significant decreased particle size of the drug in SDs. FT-IR spectroscopy demonstrated no detectable interactions between the drug and carriers. In addition to latter evidence, increased wettability and hydrophilicity of drug particles and deaggregation brought about by the carriers are the reasons for enhanced drug dissolution from the SDs. One of the possible advantages of formulating an insoluble drug such as gliclazide is that if it is used in preparation of capsules or tablets of the drug, its dose might be reduced which is economically beneficial. © 2009 Elsevier B.V. All rights reserved