Conception and Evaluation of Extended Release Multiparticulate System of Milnacipran Hydrochloride

Abstract

Milnacipran HCl is a selective norepinephrine and serotonin reuptake inhibitor well used drug for the treatment of depression and fibromyalgia. Milnacipran HCl belongs to biopharmaceutical class I having short elimination half-life. Milnacipran HCl recommended immediate release [IR] dose 50mg twice a day associated with frequent dosing which cause side effects, lack of patient compliance and discontinuation of therapy. To overcome such problems, the aim of the present study was to design novel once a day extended release multiparticulate system of Milnacipran HCl using Fluidized bed processor wurster coating technique. To achieve the goal, drug solution layering was done on seal coated #25–30 non pareil sugar spheres followed by release controlling polymer coating of Ethyl cellulose and Hydroxypropyl methyl Cellulose in the ratio 90: 10 respectively. In vitro dissolution study of 10, 12, and 14% release controlling polymer coated pellets was carried in distilled water using USP type II dissolution apparatus with sinkers. Ratio of hydrophobic to hydrophilic polymer and level of coating have highest effect on drug release. Milnacipran HCl release extended for longer duration as percent of release controlling polymer coating increased. The release kinetics was explored and explained with zero order, first order, Higuchi and Korsmeyer equations. The drug release from pellets has no significant effect of pH of dissolution medium.