Novel multi granules controlled release tablets of milnacipran: Design with simplex lattice, in-vitro characterization and pharmacokinetic predictions

Abstract

Aim: Milnacipran is well used drug for the treatment of depression and fibromyalgia. Its short elimination half-life, frequent dosing and associated side effects cause lack of patient compliance and discontinuation of present therapy. To overcome such problems, the aim of present study was to design a novel multi-granules based controlled release formulation with simplex lattice technique and study the various formulation variables. Methods: Hydrophilic polymeric and hydrophobic wax granules were prepared separately and various formulations were designed with different proportion of these granules. Results: As the proportion of hydrophobic granules in formulation increased from 0 to 100%, the mean dissolution time, time for 50% and 80% drug release extended from 4.88 to 8.95 h; 3.11 to 9.11 h and 10.51 to 20.72 h respectively. All the formulations were following first order release kinetic. Results of formulation variables indicated that viscosity of polymer, hardness of tablets and agitation speed can significantly influence the drug release from formulations and no significant effect observed for pH of dissolution media. In vitro human plasma concentrations were predicted from in-vitro release data using convolution method. Conclusion: Novel multi granule based controlled release tablet formulations of MIL were designed and evaluated for its in vitro release. Key words: Milnacipran, multi granules, controlled release, simplex lattice, convolution.