Optimization and Characterization Ezogabine-Loaded Nanosuspension for Enhancement of Bioavailability by “Bottom-Up” Technology Using 32 Factorial Design

摘要

Ezogabine, an antiepileptic drug used for treating partial epilepsies. It is poorly soluble in water. The dose ranges from 50 mg to 400 mg and the oral bioavailability is 60%. The aim of this research work was to formulate and characterize nanosuspensions of ezogabine with an intention to enhance the oral bioavailability using 3sup2/sup factorial design. Nanosuspensions were prepared by the “bottom-up” nanoprecipitation method using 3sup2/sup factorial design and evaluation for particle size, saturation solubility, zeta potential, entrapment efficiency, and in-vitro drug release was done. The FTIR was used to confirm compatibility and to rule out any possible interactions between drug and carriers. The optimal nanosuspension was obtained with particle size of 510.4 nm, saturation solubility of 557 μg/ml, zeta potential of - 4.49 mV, entrapment efficiency of 96.82%, and in-vitro drug release of 100.14%. Also, the optimal formulation was found to be stable in the accelerated conditions. Data of nanosuspensions were fit in to different equations and kinetic models and found to exhibit first order release kinetics with class II transport mechanism of diffusion. The scanning electron microscopy studies showed elongated nanoparticles with porous surface. The “Bottom up” method can be successfully employed to produce ezogabine nanosuspensions achieving reduced particle size and enhancing dissolution rate by increasing the saturation solubility and remained stable at 25 °C.