Development and evaluation of extended release formulations of isosorbide mononitrate based on osmotic technology

Extended release formulations of isosorbide mononitrate (IMN), based on osmotic technology, were developed. Target release profile was selected and different variables were optimized to achieve the same. Formulation variables like type (PVP, PEG-4000, and HPMC) and level of pore former (0-55%, w/w of polymer), percent weight gain were found to affect the drug release from the developed formulations. Drug release was inversely proportional to the membrane weight but directly related to the initial level of pore former in the membrane. Burst strength of the exhausted shells was inversely proportional to the level of pore former, but directly affected by the membrane weight. Satisfactory burst strength (more than 320 g) was obtained when PVP was used as pore former (tip to 55%, w/w of polymer) at the membrane weight of 7.5% and more. The release from the developed formulations was independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. Results of SEM studies showed the formation of pores in the membrane from where the drug release occurred. The formulations were found to be stable after 3 months of accelerated stability studies. Prediction of steady-state levels showed the plasma concentrations of IMN to be within the desired range. (C) 2003 Elsevier B.V. All rights reserved.