QBD-based systematic development of Bosentan SNEDDS: Formulation, characterization and pharmacokinetic assessment
The aim of this study was to develop self-nanoemulsifying drug delivery system (SNEDDS) of bosentan using quality by design (QBD) approach with better bioavailability. The major component of the formulation vis-à-vis lipid (CapmulMCM), surfactant (LABRASOL) and co-surfactant (PEG 600) were selected on the basis of saturation solubility. Mixture of LABRASOL and PEG 600 in the ratio of 1:1 showed better nano emulsifying regionas depicted by pseudo ternary phase diagram. The optimum mixture of Capmul MCM, LABRASOL and PEG 600 were selected by using response surface method (RSM) with central composite design (CCD). Pharmacokinetic study was conducted to determine various critical parameters. The optimized formulation showed 98.5% drug release in 15 min, globule size of 62.5 nm, emulsification time of 12 s andPDI of 0.146. TEM study revealed the drug entrapment within the oil globules of nano size range. Pharmacokinetic study of optimized formulation indicated faster dissolution and absorption which was evidenced from significantly higher Cmax, larger AUC and lower Tmax than pure drug bosentan. Thus the present study confirms potential of SNEDDS in enhancing the oral bioavailability of bosentan.