Abstract

SOLUBILITY AND DISSOLUTION RATE ENHANCEMENT OF ANTIFUNGAL VORICONAZOLE BY HOT MELT EXTRUSION AND DEVELOPMENT OF SUSTAINED RELEASE TABLETS

Sagar J. Kanase, Kishorkumar B.Burade, Ashok M.Khandekar, Ganesh R.Sawant, Aruna R. Repal

Abstract

This work studied Voriconazole27,28 solid dispersion (SD)4,5 formulation using mixture of Soluplus & KollidonVA64 melts at temperatures lower than the melting point of Voriconazole using a twin screw rotating extruder. The Voriconazole is BCS class II Antifungal drug with low aqueous solubility 1,2,3.The effects of two carriers and parameters like mixing temperature, screw rotating speed, and residence time were systematically studied. SEM, XRD, and FT-IR were employed to investigate the evolution of Voriconazole dissolution. DSC was used to quantitatively study the melting enthalpy evolution of the drug. The aqueous solubility and dissolution rate of prepared solid dispersion were significantly enhanced6,7. Thus hot-melt extrusion (HME) is a promising technology for improving solubility and dissolution profile of Voriconazole . From the prepared solid dispersion, sustained release tablets were formulated by direct compression method by using natural (Karaya gum) and semi synthetic polymers (HPMC K100M). These sustained release tablets release the drug up to 12 hours in predetermined rate. The formulated powder blend was evaluated for bulk density, tapped density, compressibility index and angle of repose. The formulated tablets were evaluated for physical characteristics of sustained release tablets such as thickness, hardness, friability, weight variation and drug content. The tablets were evaluated for In-vitro drug release studies by using USP type I dissolution test apparatus. The dissolution test was performed in 0.1 N HCL for 2 hr and phosphate buffer pH 6.8 for 10 hrs. The in-vitro cumulative drug release profile of all formulations F1-F11 at 12 hours showed 87.94% to 98.25% drug release, respectively. Formulation F6 was best formulation ,gives satisfactory release (98.25%) for 12 hours.

Keywords: Voriconazole, Hot Melt Extrusion,Soluplus, Kollidon VA 64,Karaya Gum.