Design and Development of Self-Micro Emulsifying Drug Delivery Systems of Rifaximin Using 32 Factorial Design

Aim/Background: This study aimed to enhance the oral bioavailability of Rifaximin by formulating a Self-Micro emulsifying Drug Delivery System, with the goal of improving its aqueous solubility and dissolution performance. Materials and Methods: A 3² full factorial design was applied, wherein the independent variables selected were olive oil and Tween 20, and the chosen responses were emulsification time and drug content. Rifaximin was used as a drug. Various excipients used in the formulation included oils (olive oil, coconut oil, cottonseed oil), surfactants (Tween 20, PEG 400, Span 20), co-surfactants (propylene glycol, Kolliphor RH 40), and solid carriers (microcrystalline cellulose and Aerosil 200). The prepared liquid SMEDDS were characterized by assessing their optical transparency, pH, emulsification time (34.33±1.52 to 57±1.0 sec), zeta potential(-22.7mV), globule size (98.7 to 483.3 nm), robustness to dilution, percent transmittance, viscosity, cloud point, and drug content. Solid SMEDDS were prepared using an adsorption technique. Results: The in vitro release profile showed that rifaximin from S-SMEDDS achieved 92.3624 ± 0.21% drug release, whereas the pure drug exhibited 62.8487 ± 0.24% release, indicating approximately 1.5-fold enhancement in drug release with the solid SMEDDS formulation compared to pure rifaximin. This enhanced release profile suggests improved solubility, which could potentially increase the bioavailability of Rifaximin, a drug known for its poor water solubility. Conclusion: The formulated SMEDDS significantly improved the dissolution behavior of rifaximin, which may potentially enhance its therapeutic performance. This study provides a foundation for future preclinical and clinical investigations of S-SMEDDS systems designed for poorly soluble drugs such as rifaximin.