Development and optimization of modified release formulation of nefopam hydrochloride for pain management

Abstract

Experimentation: Modified release formulation of Nefopam Hydrochloride was prepared by two different approaches i) Push-pull osmotic tablet ii) Extended release pellets in the capsule. Push-pull osmotic tablets is a bilayer tablets in which one layer contains polymer and osmogent (Push layer) and the second layer contains drug, osmogent and polymer (Drug layer) formulated by wet granulation technology. Further semipermeable membrane coating on compressed bilayer tablets which was mechanically drilled for controlled release of the drug. The critical excipients levels in the core tablet and extended release coating part were optimized using a response surface face center (and#945;=1) central composite design. Extended release pellets in capsule prepared using fluid bed processor (FBP GPCG 1.1), bottom spray (Wurster) technology. Drug loading of Nefopam Hydrochloride on core pellets followed by extended release coating which was filled in capsules. The critical excipients levels in extended release polymer layering were optimized using a response surface face center (and#945;=1) central composite design. Stability studies of both optimized formulations were carried out as per ICH Q1A (R2) guideline. Shelf life estimation of both optimized formulations was carried out by minitab 19 software and found to be stable up to 36 months. Both the optimized formulations exhibit robust performance in alcohol-induced dose dumping as well as in different In-Vitro dissolution conditions. Based on dissolution kinetic data modeling by DDsolver, push-pull osmotic tablets delivered zero order kinetic controlled drug release while extended release pellets in capsules delivered first order kinetic drug release up to 24 hrs. newlineConclusions: Modified release formulations of Nefopam Hydrochloride were successfully developed and optimized using suitable ingredients and techniques which reduce dosing frequency to minimize the side effect of the drug and improve patient compliance. Both the techniques have commercial applicability for the pharmaceutical indu