Preparation and evaluation of microspheres loaded with ranolazine for controlled release with polyacrylic polymer

Abstract

Microencapsulation of drugs in a hydrophobic matrix such as Eudragit microspheres controls the release of drugs. Eudragit polymers are series of acrylate and methacrylate polymers available in different ionic forms. Eudragit L 100 and EudragitL 100-55 are insolublein aqueous media but they are permeable and both have pH-independent release profiles.Polymer Eudragit and drug Ranolazine (earlier passed through sieve no. 100) were dissolved in specified quantity of acetone-methanol mixture. Required quantity of Aluminum stearate was added as deflocculating agent and the mixture was stirred at 500 rpm on a magnetic stirrer at 10°C. The resulting emulsion was stirred at 35°C for four  hr.  The  organic  solvent  acetone-methanol was  completely removed  by  evaporation;  finally  the  prepared solidified microspheres were filtered, and then washed 6 times with an aliquot of 50 ml n-hexane to remove all the presence of liquid paraffin from microspheres. Dissolution studies were carried out at pH 1.2 HCl buffer for 2 hrs followed by 7 hrs in pH 7.4 phosphate buffer using USP XXI dissolution apparatus type II(basket type). Dissolution media having volume of 900ml was kept at 37ºC ± 0.5 ºC. Initial drug release from Eudragit microspheres at intestinal environment by biphasic manner and associated with an initial burst release of 21.27 % to 74.94 %, 10.19% to 67.57 %, 8.35 % to 61.53 %, 27.92 % to 75.69 %, 31.32 % to 72.37 % and 37.48 % to 65.89 % drug from F1, F2, F3, F4, F5 and F6 microspheres respectively. The burst release in intestinal pH might be due to the release of surface accumulated drug. After initial burst effect, the subsequent release of drug was slow and sustained. F1 formulation can be supposed to be the optimized formulation. This optimization can be attributed to good percent release of drug at end of 9th  hour. Also F1 formulation has shown a good consistency in shape, sphericity and uniformity in the preparation of microspheres.