FORMULATION AND CHARACTERIZATION OF PARENTERAL IN SITU IMPLANTS OF TARIQUIDAR BIMESYLATE

The objective of present study was to formulate and evaluate Tariquidar bimesylate subcutaneous in situ implants in order to minimize the frequency of doses and toxicity and to improve the therapeutic efficacy. The anthranilic acid derivative, tariquidar (XR9576), is a potent and selective P-gp inhibitor being developed clinically for the treatment of multidrug resistant tumors. Tariquidar bimesylate in situ implants were prepared by polymer precipitation method using two different grades of polymer poly (Lactide -co-glycolide) (PLGA) with three different concentrations. The preparation involves dissolving the biodegradable polymer poly (Lactide -co-glycolide) PLGA 85:15 and PLGA 75:25 in N-methyl-2- pyrrolidone. To this solution drug was added and the polymer drug solution was injected in to the aqueous mediato forma solid implant. Based on initial burst release, optimized formulations were selected and evaluated for surface morphology, in vitro drug release and accelerated stability studies. It was observed that the formulations with more polymer concentration and in combination with polyethylene glycol(PEG) and Benzy l benzoate (BB) showed increased entrapment efficiency and exhibited moderate burst release and sustained release for 156 hrs. Release kinetics was calculated for optimized formulations and the formulation F10, F11, F12, F13 followed Higuchi kinetics with nonfickian diffusion. Optimum use of various polymers along with benzyl benzoate and polyethylene glycol can result in better sustained release for Tariquidar bimesylate and can be explored for therapeutic benefit in Multidrug resistant tumors.