Development and Characterization of Leflunomide-Loaded Self-micro Emulsifying Drug Delivery System (SMEDDS) for Enhancement of Solubility

Leflunomide, a Biopharmaceutical Classification System Class II drug candidate which exhibits low solubility and high permeability, that can limit its bioavailability. To address this issue, the present study explores the development of a Self-Micro Emulsifying Drug Delivery System (SMEDDS) of Leflunomide to improve solubility. A systematic screening of different oils, surfactants, and co-surfactants was performed to identify optimal components for the SMEDDS formulation. Among the evaluated excipients, Saturation solubility studies show Captex 200 (113.15±1.2mg/mL) as the most effective oil for solubilizing Leflunomide, followed closely by Transcutol P (98.65±2.8mg/mL) as an oil, and Tween 80 (90.82±1.2mg/mL) as a surfactant. Pseudoternary phase diagrams were constructed using various surfactant and co-surfactant ratios to determine the optimal microemulsion area. The D - optimal experimental design was employed using oil, S-mix, and water as independent variables, and the globule size and drug loading were selected as key responses. The best performing batch (Run 6) demonstrated maximum drug loading (99.5%) and minimal globule size (78nm), confirming the effectiveness of the design in achieving an ideal balance between drug loading and globule size. The Zeta potential analysis (−23.15mV) confirmed the stability of the SMEDDS. The study showed promise in enhancing solubility and is expected to improve oral bioavailability due to the nanoscale size. These findings suggest the potential of SMEDDS-based delivery for achieving time-targeted therapy in rheumatoid arthritis, aligning drug release with the circadian rhythm of disease symptoms.