preparation and evaluation of novel ketoconazole floating and sustained release matrix tablet

Abstract

Introduction: Ketoconazole is one of the basic widely used untifungal drugs that has low solubility in intestinal lumen. Lower bioavailability of it is related to this fact. Retaining of ketoconazole in stomach may cause obtaining better dissolution rate and then better bioavailability. Aim: Preparing a floating system of this drug may increase the residence time of the device the stomach and causing increased bioavailability. Material and Methods: Various formulations were designed. HPMC, psyllium and carbomer in different concentrations were used as floating agents. As a gas forming agent ,cacarbonate was utilized in the formulations .Prepared tablets were investigated from the view points of hardness, friability and floating properties (time for starting and duration of floating). Floating and release profiles were studied using USP apparatus II in HCl 0.1 N . Results: Formulations that contain psyilliumas filler showed prolonged lag time for buoyancy duration. Adding carbomer to these formulations not only reduced relative lag times but also kept their proper buoyancy duration times. Formulations that containing HMPC did not show proper buoyancy duration time. Adding psyllium caused better floating duration time. Conclusion: Selected formulations were able to float at the proper time after contacting with gastric fluids and remained floated for at least 8 hours. During this period, sustained release profile of the drug was obtained and leads to increase in bioavailability of ketoconazole .because of ketoconazole has liver first pass ,formulation that have less floating time are more desirable ,because the liver enzymes rapidly saturated and the drug passes intact .in this case formulations of 1 ,2 ,4 and 5 are accepted .