Experimental Design for Optimization of Felbamate Nanosuspension Using Box-Behnken Design.

Abstract

Felbamate, a valuable antiepileptic drug, suffers from low water solubility and potential side effects, limiting its therapeutic application. This study addresses this challenge by developing a felbamate nanosuspension for nose-to-brain delivery using a three-factor, three-level Box-Behnken design. The research focused on identifying the optimal combination of key formulation variables, chitosan concentration, chitosan/sodium tripolyphosphate ratio, and Tween 80 surfactant concentration to achieve a nanosuspension with desirable particle size, polydispersity index, and high entrapment efficiency (%EE), all critical parameters for efficient drug delivery via the nasal route. The study identified an optimized formulation consisting of 0.176% chitosan, a 3.3:1 chitosan/TPP ratio, and 1.55% Tween 80 through rigorous experimentation and response surface methodology analysis. The optimized formulation yielded a nanosuspension of 115.0 ± 4.37 nm mean particle size, 0.118 ± 0.021 polydispersity index, and +34.08 ± 2.4 mV zeta potential, indicating a stable system with a narrow size distribution suitable for enhanced drug delivery. The entrapment efficiency of 93.18 ± 1.69% confirmed effective encapsulation, while in-vitro dissolution studies demonstrated a significantly higher dissolution rate compared to pure felbamate, suggesting improved bioavailability. The results emphasize the capacity of this optimized nanosuspension to improve the therapeutic efficacy of felbamate and hence justify additional preclinical and clinical research.