Self Micro-Emulsifying Drug Delivery System for Lymphatic Uptake of Darunavir

The aim of the present study was to target Darunavir (DRV); an antiretroviral Protease Inhibitors (PI) drug to lymphatic system using Self Micro Emulsifying Drug Delivery System (SMEDDS) to increase its solubility and bioavailability. SMEDDS system compromising of Imwitor 988 as oil phase, Tween 20 and Span 20 as binary surfactant system were optimized with respect to drug solubilization, particle size, zeta potential, dispersibility, optical clarity, cloud point, in-vitro release and thermodynamic stability. The selected formulation was subjected to ex-vivo lymphatic uptake studies using everted sac method in presence and absence of lymphatic uptake blocker Pluronic-F68. In-vivo pharmacokinetic studies were performed and lymphatic transport of DRV SMEDDS was studied. SMEDDS system containing Imwitor 988 (20%) and Surfactant mix (Smix) (80%) showed maximum drug solubility with least particle size. The ex-vivo lymphatic uptake studies of DRV loaded SMEDDS in presence of lymphatic uptake blocker showed 36.69% drug permeation which increased to 64.24% in absences of lymphatic blocker, indicating the drug transport by lymphatic path. Cmax of DRV loaded SMEDDS was higher as compared to marketed tablet. Also, Pluronic F68 treated rats show lesser plasma concentration as compared to those administered with SMEDDS. The results suggest that SMEDDS is a promising drug delivery system to improve solubility and lymphatic transport of anti-HIV drug DRV.