Self microemulsifying drug delivery system of lurasidone hydrochloride for enhanced oral bioavailability by lymphatic targeting: In vitro, Caco 2 cell line and in vivo evaluation.
The global aim of this research was to develop and evaluate self microemulsifying drug delivery system (SMEDDS) to improve oral bioavailability of Lurasidone Hydrochloride (LH) A chylomicron flow blocking approach was used to evaluate lymphatic drug transport. The developed LH SMEDDS composed of Capmul MCM C8 (oil) Cremophor EL (surfactant) and Transcutol HP (co surfactant) Highest microemulsifying area was obtained at 3:1 ratio (surfactant:cosurfactant)and mean globule size was found to be 49.22 1.60 nm. More than 98% drug release was obtained with LH SMEDDS as that of LH suspension. Confocal microscopy and flow cytometry studies reveled higher fluorescence indicating deeper penetration across Caco 2 cells with coumarin 6 SMEDDS as compared to coumarin 6 solution. Mean Fluorescence Intensity (MFI) with coumarin 6 loaded SMEDDS was increased 25.57 times with respect to coumarin 6 solution. The permeability across Caco 2 cells was enhanced 3 times with LH SMEDDS as compared to LH suspension. Furthermore, Area under curve with LH SMEDDS was found to be 2.92 times higher than that of LH suspension indicating improved bioavailability after formulating SMEEDS. Lymphatic transport in oral absorption of LH SMEDDS was proved via lymphatic uptake study. All the findings suggest the effectiveness of lipid based formulation i.e. SMEDDS of LH to augment the oral bioavailability via intestinal lymphatic pathway.
European journal of pharmaceutical sciences official journal of the European Federation for Pharmaceutical Sciences