Optimization and Evaluation of Micromeritic and Release Properties of High Dose Flutamide Liquisolid Systems

Kadria      A. Elkhodairy; Wael      M. Samy

Abstract

Flutamide (FLT) is the only presently recommended drug for monotherapy of benign prostatic hypertrophy. It is known for its poor solubility and slow dissolution. In this study nine different formulae of liquisolid systems (LS) were prepared using Polyethyleneglycol 400 as a liquid vehicle, Avicel® PH 102 and Aerosil 200 as the carrier and the coating material, respectively. Hydrophilic polymers (PVP, HPMC and PEG 2000) were added at a 10% w/w concentration to improve LS properties. Thermal analysis showed complete absence of drug crystallinity in the prepared LS that indicates successful FLT solubilization. The prepared systems were tested for their micromeritic properties (angle of repose, Carrs index and Hausners ratio). The results showed that all the formulae had acceptable values of the angle of repose except formulae F2 (42.0) and F3 (43.50) indicating reasonable flow properties of the LS systems. Compressed into tablets, formula F8 showed the fastest drug release with about 69% of the drug released after the first 5 minutes and almost all the drug released after one hour. Directly compressed FLT tablets showed very slow release with only 5% and 30% of the drug released after 5 and 120 minutes, respectively.

Keywords: Flutamide, Liquisolid systems, PEG 400, PVP, HPMC, PEG 2000, Dissolution rate, FLT, Microsystems, “powdered solution technology”, dry-looking, polyvinyl pyrrolidone (PVP), liquid load factor (Lf), sodium starch glycolate (Explotab), Precompression Studies, Differential Scanning Calorimetry (DSC)