Formulation and Optimization of Self Emulsifying Drug Delivery System for Enhanced Solubility and Oral Bioavailability of Amisulpride Using Design of Expert Approach

Background

Amisulpride, a Biopharmaceutics Classification System (BCS) Class II antipsychotic drug, exhibits limited aqueous solubility, resulting in poor dissolution and suboptimal oral bioavailability. Self-Emulsifying Drug Delivery Systems (SEDDS) represent an effective lipid-based strategy for improving the solubilization and gastrointestinal absorption of poorly water-soluble drugs. This study aimed to formulate and optimize an Amisulpride-loaded SEDDS using a Quality by Design approach based on Box-Behnken Design (BBD).

Materials and Methods

Solubility screening was performed to identify suitable formulation components, leading to the selection of oleic acid as the oil, Tween 80 as the surfactant, and PEG 400 as the co-surfactant. A three-factor, three-level Box-Behnken experimental design comprising 15 formulations was employed to optimize the formulation. The prepared SEDDS were characterized for globule size, polydispersity index, zeta potential, percentage transmittance, self-emulsification time, and in vitro drug release. The optimized formulation was further evaluated for robustness to dilution, cloud point, thermodynamic stability, transmission electron microscopy, and drug release kinetics.

Results

The optimized formulation demonstrated a mean globule size of 157.1±0.32 nm, a polydispersity index of 0.272±0.012, and a zeta potential of -42.11±5.64 mV, indicating the formation of a stable nanoemulsion. The formulation exhibited excellent clarity with approximately 100% transmittance, rapid self-emulsification within 36±1 s, and a cumulative drug release of 98.18±2.06% after 55 min. Numerical optimization yielded an overall desirability value of 0.953, confirming the suitability of the optimized composition. Stability studies, dilution robustness, and cloud point evaluation demonstrated that the optimized SEDDS remained physically stable without precipitation or phase separation. Drug release data were best described by the first-order kinetic model.

Conclusion

The Box-Behnken Design successfully optimized an Amisulpride-loaded SEDDS with desirable physicochemical properties, rapid emulsification, excellent dissolution behavior, and good thermodynamic stability. The developed formulation has considerable potential to improve the oral performance of Amisulpride and illustrates the usefulness of Design of Experiments for the systematic development of lipid-based drug delivery systems.