Abstract

Nebivolol HCl (NBL) a third generation beta blocker poses lack of oral bioavailability (12%) owing to its low solubility and first pass biotransformation in liver. The present research was undertaken to prepare solid Selfnanoemulsifying drug delivery system (S-SNEDDS) of NBL which will present NBL at molecular level in nanoemulsion form throughout GIT. Increased solubility along with intestinal lymphatic transport of lipid rich nanoemulsified drug bypassing hepatic first pass may enhance bioavailability. Based on solubilization of the drug and spontaneity of selfemulsification, Peceol as an oily phase, Cremophore RH 40 and Gelucire 50/13 as surfactants and ethanol as cosurfactant/ co-solvent were selected as the excipients to produce NBL loaded S-SNEDDS. Total 9 formulations were made with different ratios of the excipients and the optimized formulation was selected on the basis of solidification of SNEDDS on refrigeration and maintenance of the solid state. Spherical shaped morphology of oil globules was confirmed by TEM analysis. On dilution S-SNEDDS showed nanoparticles of size 180-190nm with a Polydispersity index 0.4-0.8 and Zeta potential -5.17, -7.56mV. The DSC and X-ray diffraction patterns of the S-SNEDDS show the amorphous state of NBL in the lipid matrix. Developed S-SNEDDS showed pH-independent drug dissolution which in SIF was fourfold greater as compared to plain drug. The intestinal permeability by everted sac technique showed threefold increase in transportation of NBL from S-SNEDDS formulation compared to NBL solid suggesting that S-SNEDDS of NBL is an excellent and practical approach of enhancing the oral bioavailability through improved solubility.

Keywords: Cremophore RH 40, gelucire 50/13, nebivolol hydrochloride, oral bioavailability, peceol, solid self-emulsifying drug delivery system.

Graphical Abstract