Formulation and Characterization of Self Micro-Emulsifying Drug Delivery System of Cyclosporine.

Cyclosporine (CyA), a potent immunosuppressant, faces significant formulation challenges due to its low aqueous solubility and poor oral bioavailability. The objective of this study was to develop and optimize a lipid-based self-microemulsifying drug delivery system (SMEDDS) using a Quality by Design (QbD) approach to enhance the solubility and delivery profile of CyA. Preliminary solubility studies identified cinnamon oil as the optimal lipid phase (6.92 mg/mL solubility), while Tween 80 and propylene glycol were selected as the surfactant and co-surfactant, respectively. A Central Composite Design (CCD) was employed to evaluate the effects of surfactant (A) and co-surfactant (B) concentrations on particle size, drug content, and drug release. The optimized formulation (F5), containing 0.1 mL cinnamon oil, 0.05 mL Tween 80, and 0.05 mL propylene glycol, exhibited a nanometric particle size of 22.8 nm with a narrow polydispersity index (0.143) and a stable zeta potential of –26.5 mV. Drug content was found to be 96.15%, with ANOVA revealing that the co-surfactant concentration significantly influenced drug incorporation. In vitro dissolution studies showed that F5 achieved a maximum cumulative drug release of 96.51% over 8 hours, following zero-order kinetics (R2 = 0.9724), indicating a constant drug release rate. Thermodynamic stability tests, including freeze-thaw cycles and centrifugation, confirmed the robustness of the system. FTIR analysis verified the chemical compatibility between CyA and excipients, while TEM imaging confirmed the formation of uniform, spherical droplets. This study demonstrates that the optimized cinnamon oil-based SMEDDS is a promising vehicle for the stable and efficient oral delivery of Cyclosporine.