| Ketoconazole is widely prescribed drug to treat fungal infections. However, due to its hydrophobic nature in gastro-intestinal fluids, variations in bioavailability have been documented. Therefore, to enhance its dissolution, this study was initiated to develop and evaluate solid dispersion form of the drug.;In the present investigation, an attempt were made to improve the solubility and dissolution rate of a poorly soluble drug, Ketoconazole by solid dispersion method using mannitol, polyethylene glycol (PEG) 4000 and polyethylene glycol 8000, polyvinyl pyrrolidone K-30, polyvinyl pyrrolidone K-17, kollidone VA 64, poloxamer 188 and succinic acid as carrier. Solid dispersion of Ketoconazole was prepared by solvent evaporation. In vitro release profiles of all Solid dispersions were comparatively evaluated and also studied against pure Ketoconazole. Faster dissolution was exhibited by solid dispersion containing 1:3 ratio of drug: pvp k-17 by solvent evaporation method. The prepared solid dispersions were subjected for percent practical yield, drug content, Infra-Red (I.R.) spectroscopic studies and differential scanning calorimetry (DSC). FT-IR spectra revealed no chemical incompatibility between drug and polymer. Drug - polymer interactions were investigated using differential scanning calorimetry (DSC).;In vitro dissolution studies reveal that there is an increase in both the quantity of drug solubilized and the rate of dissolution after formulation into their solid dispersions. The stability studies for two months under various temperatures (30°C, 35°C, 40°C, and 45°C) and relative humidity conditions (100%, 75.29 +/-0.12%, 54.38 +/-0.23 and 23.11 +/-0.25% RH) indicated that the formulations might be stable.;The accelerated stability studies also helped to determine the trends with the shelf life of the formulations using the Arrhenius equation. The Dispersion with drug to PVP at a ratio of 1:3 proved to be an appropriate formulation to optimize the drug dissolution of Ketoconazole. This formulation is expected to show a better in-vivo/in-vitro correlation, thus minimizing the bioavailability variations with the oral use of this clinically important drug. |
