Design, Optimization and In-Vitro Characterization of Gamma Oryzanol-Loaded Self-Nanoemulsifying Drug Delivery System (SNEDDS) using Box-Behnken Design
TL;DR
The developed SNEDDS significantly improved the dissolution characteristics of Gamma Oryzanol and may serve as an effective lipid-based delivery platform for enhancing the oral performance of poorly water-soluble bioactive compounds.
Abstract
Gamma Oryzanol is a bioactive phytoconstituent with promising antioxidant, anti-inflammatory, and therapeutic properties; however, its clinical application is limited by poor aqueous solubility, slow dissolution rate, and low oral bioavailability. The present study was undertaken to develop and optimize a Self-Nanoemulsifying Drug Delivery System (SNEDDS) for improving the solubility and dissolution behavior of Gamma Oryzanol. A Box-Behnken Design (BBD) integrated with response surface methodology was employed using Design-Expert software to optimize the formulation variables. Three formulation components, namely olive oil (X1), Tween 20 (X2), and PEG 400 (X3), were selected as independent variables, while droplet size (Y1) and turbidity (Y2) were considered as dependent responses. A total of 17 experimental runs were generated and analyzed to establish the relationship between formulation variables and response characteristics. Numerical optimization using the desirability function approach identified an optimized formulation containing olive oil, Tween 20, and PEG 400 in a ratio of 40:40:20. The optimized SNEDDS exhibited a droplet size of 60.44 ± 0.23 nm and a polydispersity index of 0.489, indicating the formation of a uniform nanoemulsion system. Thermodynamic stability studies confirmed the robustness of the formulation under various stress conditions, while dispersibility studies demonstrated rapid self-emulsification with excellent clarity. In vitro dissolution studies revealed a remarkable enhancement in drug release from the optimized SNEDDS, achieving 98.2% cumulative drug release within 60 minutes compared to only 29.1% release from pure Gamma Oryzanol. Furthermore, kinetic modeling indicated that the release profile was best described by the Korsmeyer–Peppas model (R² = 0.9912), suggesting a diffusion-controlled release mechanism. The findings of the present study demonstrate that the developed SNEDDS significantly improved the dissolution characteristics of Gamma Oryzanol and may serve as an effective lipid-based delivery platform for enhancing the oral performance of poorly water-soluble bioactive compounds.