Development and Optimization of Nefopam Hydrochloride Push-Pull Osmotic Pumps by Design of Experiments

Abstract

Nefopam hydrochloride (NFH) is one of the centrally acting NSAIDs drug used for pain management. The main objective of this research is to study the effect of ratio of Cellulose acetate: Polyethylene glycol (PEG) 3350, and %weight gain in extended release (ER) coating of push-pull osmotic pump (PPOP) tablets, optimized by the design of experiment (DoE) using response surface face center (α=1), the central composite design having two independent variables at three levels. PPOP tablets of NFH were administered once a day to reduce dosing frequency and improve patient compliance. PPOP tablets contain drug and push layers, compressed into bilayer tablets, coated with cellulose acetate (CA) as semipermeable membrane polymer, and PEG 3350 as a plasticizer or pore-forming agent. ER coated tablets mechanically drill ~0.50 mm on the drug layer part for the controlled release of the drug up to 24 hrs. Based on the results, the ratio of CA: PEG 3350 and % weight gain in ER coating of PPOP tablets shows a significant impact on % drug release. At lower % of PEG, burst release was observed due to cracking of ER coating layer, while at higher % of PEG, slightly rapid release of drug was observed. %Drug release is decreased with an increase in the %weight gain of tablets. PPOP Tablets with 10% PEG 3350 (Ratio of CA:PEG 3350, 90:10) and 8% weight gain exhibit zero-order kinetic drug release up to 24 hours.