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.

Keywords::

• bioavailability
• in situ perfusion
• pharmacokinetic study
• polymeric precipitation inhibitor

Acknowledgements

The authors would like to thank Prof. B.G Shivananda for his advice and support in carrying out this research. The authors gratefully acknowledge the financial support and the research fellowship grant (45/38/2011/Nan-BMS) from ICMR (Indian Council of Medical Research, Government of India, New Delhi). The authors are also grateful to Sami Labs, Bangalore, India, for providing the gift sample of trans-resveratrol.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.