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 design of experiment (DoE) using response surface face center (α=1), central composite design having two independent variables at three levels. PPOP tablets of NFH was administer once in a day to reduce dosing frequency and improve patient compliance. PPOP tablets contains drug layer and push layer, compressed in to bilayer tablets which is further coated with cellulose acetate (CA) as semipermeable membrane polymer and PEG 3350 as a plasticizer or pore forming agent. ER coated tablets mechanically drill ~0.50mm on drug layer part for the controlled release of drug up to 24 hrs. Based on the results it can be concluded that the ratio of CA: PEG 3350 and % weight gain in ER coating of PPOP tablets shows 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 decrease with increase in the % weight gain of tablets. PPOP Tablets with 10% of PEG 3350 (Ratio of CA:PEG 3350, 90:10) and 8% weight gain exhibits zero order kinetic drug release up to 24 hrs.
Keywords:
Nefopam hydrochloride (NFH), Push-pull osmotic pump (PPOP) tablet, Cellulose acetate (CA), Polyethylene glycol (PEG) 3350, Design of Experiment (DoE), Response surface central composite designDOI
https://doi.org/10.25004/IJPSDR.2021.130408References
Gujral G, Kapoor D, Jaimini M.An updated review on modified release tablets. J Drug DelivTher. 2018;8(4):5-9.
Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, Keefe FJ, Mogil JS, Ringkamp M, Sluka KA, Song X, Stevens B, Sullivan MD, Tutelman PR, Ushida T, Vader K. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. PAIN. 2020;161(9):1976–1982.
Paice JA. Mechanisms and management of neuropathic pain in cancer. J Support Oncol. 2003;1(2):107-20.
Debono DJ, Hoeksema LJ, Hobbs RD. Caring for patients with chronic pain: pearls and pitfalls. J Am Osteopath Assoc. 2013;113(8):620-627.
Turk DC, Dworkin RH. What should be the core outcomes in chronic pain clinical trials?. Arthritis Res Ther. 2004;6(4):151–154.
Breivik H, Borchgrevink PC, Allen SM, Rosseland LA, Romundstad L, Hals EK, Kvarstein G, Stubhaug A. Assessment of pain. Br J Anaesth. 2008;101(1):17-24.
Moore RA, Wiffen PJ, Derry S, Maguire T, Roy YM, Tyrrell L. Non-prescription (OTC) oral analgesics for acute pain - an overview of Cochrane rev iews. Cochrane Dat abase Syst Rev. 2015; 11(11):CD010794.
Park HJ, Park JU, Yoo W, Moon YE. Analgesic effects of nefopam in patients undergoing bimaxillary osteotomy: A double-blind, randomized, placebo-controlled study. J Craniomaxillofac Surg. 2016;44:210-214.
Yu J, Solon E, Shen H, Modi NB, Mittur A. Pharmacokinetics, distribution, metabolism, and excretion of the dual reuptake inhibitor [14C]-nefopam in rats. Xenobiotica. 2016;46(11):1026- 1048.
Girard P, Chauvin M, Verleye M. Nefopam analgesia and its role in multimodal analgesia: A review of preclinical and clinical studies. ClinExpPharmacol Physiol. 2016;43(1):3-12.
Uphade KB, Patil PB, Saudagar RB. Formulation, development and in-vitro evaluation of osmotic tablet of nefopam hydrochloride. Int J Res Advent Technol. 2018;6(7):1672-1680.
Sukhbir S, Yashpal S, Sandeep A. Development and statistical optimization of nefopam hydrochloride loaded nanospheres for neuropathic pain using Box–Behnken design. Saudi Pharm J. 2016;24:588-599.
Sharma N, Arora S, Madan J. Nefopam hydrochloride loaded microspheres for post-operative pain management: synthesis, physicochemical characterization and in-vivo evaluation. Artif Cells NanomedBiotechnol. 2018;46(1):138-146.
Qin C, He W, Zhu C, Wu M, Jin Z, Zhang Q, Wang G, Yin L. Controlled release of metformin hydrochloride and repaglinide from sandwiched osmotic pump tablet. Int J Pharm. 2014;466:276-285.
Emara LH, Taha NF, El-Ashmawy AA, Raslan HM, Mursi NM. Controlled porosity osmotic pump system for the delivery of diclofenac sodium: In-vitro and in-vivo evaluation. Pharm Dev Technol. 2014;19(6):681-691.
Politis SN, Colombo P, Colombo G, Rekkas DM. Design of experiments (DoE) in pharmaceutical development. Drug DevInd Pharm. 2017;43(6):889-901.
Gujral G, Kapoor D, Jaimini M. An updated review on design of experiment (DoE) in pharmaceuticals. J Drug DelivTher. 2018;8(3):147-152.
Shah A, Shah V, Upadhyay UM. Development and evaluation of push-pull based osmotic delivery system for ropinirole. Int J Pharm Sci. Res. 2012;3(09):3211-3218.
Li Y, Pan H, Duan H, Chen J, Zhu Z, Fan J, Li P, Yang X, Pan W. Double-layered osmotic pump controlled release tablets of actarit: In vitro and in vivo evaluation. Asian J Pharm Sci. 2019;14:340-348.
Published
Abstract Display: 581 
PDF Downloads: 477 
