Solubilization of vardenafil HCl in lipid-based formulations enhances its oral bioavailability in vivo: A comparative study using Tween - 20 and Cremophor - EL

Abstract

The aim of the present investigation was to develop and characterize a promising oral drug delivery system for vardenafil HCl trihydrate (VDN), a poorly soluble drug. For this, self-microemulsifying drug delivery system (SMEDDS) was prepared. Capmul MCM C8 showing highest solubilization capacity was selected as oil. Self-microemulsifying capacity of two surfactants viz. Cremophor EL and Tween 20 were compared for the selected oil phase. Comparing the size of the reconstituted emulsions obtained by small angle neutron scattering (SANS) and Cryo-TEM with that from dynamic light scattering (DLS), it was found that actual core size of oil globule was much smaller than the hydrodynamic diameter. Owing to more number of carbons, Cremophor EL based system was more viscous than Tween 20 VDN SMEDDS. In vitro dissolution and ex vivo permeation study showed superior performance of SMEDDS over drug suspension. In vitro toxicity study using MTT dye on CaCO2 cell line indicated safety of the drug and formulation. Endocytosis and perinuclear localization of SMEDDS system was qualitatively confirmed by cellular uptake study using Coumarin 6 fluorescent dye. In vivo performance was assessed by cryo-sectioning of intestinal tissue and pharmacokinetics. Compared to Cremophor-EL VDN SMEDDS, Tween 20 VDN SMEDDS showed 2.8-fold increase in bioavailability owing to smaller globule size, enhanced dissolution and permeation ability. The encouraging results of SMEDDS suggests its potential application for oral delivery of VDN for treatment of erectile dysfunction.