Combination of floating system & co-grinding technologies for enhancing dissolution rate of ketoconazole

Abstract

Ketoconazole is an antifungal drug that has a low solubility in the lumen of the intestine. The intestine is the most appropriate place for absorbtion of most medications. So retaining of ketoconazole in the stomach and using cogrinding method may cause getting better dissolution rate and hence bioavailability. Aim: Combination of floating system and cogrinding technologies for enhancing dissolution rate of ketoconazole. Materials and Methods: Different formulations were designed. HPMC, psyllium and carbomer in various concentrations were used as polymers. As a gas forming agent, calcium carbonate was added in the formulations. Also various ratios of lactose were applied in this formulation. Ball mill method was used for preparation of co-grinded mixture. The prepared tablets were tested from the view points of hardness, friability and floating properties.Release profiles were also investigated. Results: Formulations that had an equal amount of 3 polymers ,showed a prolonged lag time for buoyancy duration and those that contained high amount of psyllium did not show proper buoyancy duration time. Adding Carbomer to formulations caused short lag time and also increased buoyancy duration times. F1-F2-F4-F5 that contained HPMC, psyllium or both of them had acceptable results, and at the end of 3 hours released a significant amount of their contained drugs. F4 and F5 did not have proper floating prpperties. In addition, appliying cogrinding method has been able to significantly increase drug release rate. Conclusion: Selected formulations, were able to show proper buoyancy behavores, leading to increased drug release in the stomach and hence enhanced bioavailability expected.