title: Development and statistical optimization of nefopam hydrochloride loaded nanospheres for neuropathic pain using Box-Behnken design.
abstract: Nefopam hydrochloride (NFH) is a non-opioid centrally acting analgesic drug used to treat chronic condition such as neuropathic pain. In current research, sustained release nefopam hydrochloride loaded nanospheres (NFH-NS) were auspiciously synthesized using binary mixture of eudragit RL 100 and RS 100 with sorbitan monooleate as surfactant by quasi solvent diffusion technique and optimized by 35Box-Behnken designs to evaluate the effects of process and formulation variables. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetric (DSC) and X-ray diffraction (XRD) affirmed absence of drug-polymer incompatibility and confirmed formation of nanospheres. Desirability function scrutinized by design-expert software for optimized formulation was 0.920. Optimized batch of NFH-NS had mean particle size 328.36 nm ± 2.23, % entrapment efficiency (% EE) 84.97 ± 1.23, % process yield 83.60 ± 1.31 and % drug loading (% DL) 21.41 ± 0.89. Dynamic light scattering (DLS), zeta potential analysis and scanning electron microscopy (SEM) validated size, charge and shape of nanospheres, respectively.In-vitrodrug release study revealed biphasic release pattern from optimized nanospheres. Korsmeyer Peppas found excellent kinetics model with release exponent less than 0.45. Chronic constricted injury (CCI) model of optimized NFH-NS in Wistar rats produced significant difference in neuropathic pain behavior (p< 0.05) as compared to free NFH over 10 h indicating sustained action. Long term and accelerated stability testing of optimized NFH-NS revealed degradation rate constant 1.695 × 10-4and shelf-life 621 days at 25 ± 2 °C/60% ± 5% RH.
authors.affiliation: Department of Research, Innovation and Consultancy, Punjab Technical University, Jalandhar-Kapurthala Highway, Kapurthala 144603, Punjab, India; Chitkara College of Pharmacy, Chitkara University, Chandigarh Patiala National-Highway (NH-64), Rajpura, Patiala 140401, Punjab, India.
authors.forename: S
authors.initials: S
authors.lastname: Sukhbir
authors.affiliation: Lord Shiva College of Pharmacy, Sirsa 125055, Haryana, India.
authors.forename: S
authors.initials: S
authors.lastname: Yashpal
authors.affiliation: Chitkara College of Pharmacy, Chitkara University, Chandigarh Patiala National-Highway (NH-64), Rajpura, Patiala 140401, Punjab, India.
authors.forename: A
authors.initials: A
authors.lastname: Sandeep
keywords: Box–Behnken design; Nefopam hydrochloride; Neuropathic pain; Solvent diffusion