title: In vitro and in vivo performance of supersaturable self-nanoemulsifying system of trans-resveratrol.
abstract: To develop an optimized supersaturable self-nanoemulsifying drug delivery system (S-SNEDDS) in order to improve the oral bioavailability of trans-resveratrol (t-RVT), together with surmounting poor aqueous solubility, enterohepatic recirculation and controlling drug precipitation, by employing a precipitation inhibitor (PPI) that is, hydroxypropyl methylcellulose (HPMC). The long-term stability of a previously reported formulation optimized long chain triglycerides (OPT LCT-SNEDDS), consisting of Lauroglycol FCC and Transcutol P, indicated rapid precipitation of trans-resveratrol. Following incorporation of the selected PPI, the precipitates were differentiated using the X-ray diffraction (XRD) technique. An in vitro supersaturation test was carried out for the S-SNEDDS formulation. The S-SNEDDS formulation was appraised for pharmacokinetic and in situ perfusion studies. In vitro dilution of the S-SNEDDS formulation resulted in the formation of a nanoemulsion, followed by a slow precipitation of t-RVT in the S-SNEDDS formulation vis-à-vis SNEDDS formulated with OPT-LCT, where it undergoes rapid precipitation, yielding a low t-RVT concentration. The pharmacokinetic study indicated that the AUC(0-8h) of the S-SNEDDS formulation increased by nearly 1.33-fold in the presence of HPMC vis-à-vis the OPT LCT-SNEDDS, at a drug dose of 20 mg/kg. The in situ perfusion parameters, viz., fraction absorbed and effective permeability, demonstrated significant improvement in the rate and extent of absorption from the S-SNEDDS formulation. This case demonstrates that the supersaturatable approach is effective in delivering and in improving the oral bioavailability of t-RVT.
authors.affiliation: a Department of Pharmaceutics , Faculty of Pharmacy, Al-Ameen College of Pharmacy , Bangalore , Karnataka , India.
authors.forename: Gurinder
authors.initials: G
authors.lastname: Singh
authors.affiliation: a Department of Pharmaceutics , Faculty of Pharmacy, Al-Ameen College of Pharmacy , Bangalore , Karnataka , India.
authors.forename: Roopa S
authors.initials: RS
authors.lastname: Pai
mesh_terms: D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004655:Emulsions; D065347:Hypromellose Derivatives / Q000737:chemistry; D007408:Intestinal Absorption; D008297:Male; D049329:Nanostructures / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D012995:Solubility; D013267:Stilbenes / Q000737:chemistry* / Q000493:pharmacokinetics*; D014280:Triglycerides / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D013267:Stilbenes; D014280:Triglycerides; D014867:Water; D065347:Hypromellose Derivatives; D000077185:Resveratrol
keywords: bioavailability; in situ perfusion; pharmacokinetic study; polymeric precipitation inhibitor