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.

Wound healing effects of nanoemulsion containing clove essential oil

“…Recently, oral nanoemulsions have been investigated as potential vehicles for enhancing therapeutic activities and bioavailability of various biologically active drug molecules (Laxmi et al 2015, Obitte et al 2014, Singh and Pai 2016, Thomas et al 2012. Nanoemulsions are thermodynamically stable lipid based drug delivery systems which are composed of oil, surfactant, cosurfactant, and water having the droplet size in the magnitude of nanometers .…”

Effect of dobutamine on extravascular lung water index, ventilator function, and perfusion parameters in acute respiratory distress syndrome associated with septic shock

“…Th e authors alone are responsible for the content and writing of the paper. negative or aggravated signs in hypotension or hemodynamic parameters (Singh and Pai 2014). Despite the lack of diff erences in SvO 2 , arterial lactate, and oxygen delivery, the improvement in urine output and in the doses of norepinephrine indicate benefi cial eff ects on tissue hypoperfusion.…”

Bioavailability Improvement Strategies for Poorly Water-Soluble Drugs Based on the Supersaturation Mechanism: An Update

“…In addition to the precipitation inhibition effect, the inclusion of HPMC E5LV in the S-SNEDDS can significantly reduce the excretion effect of P-glycoprotein and multi-resistant proteins to improve systemic exposure levels of the model drug ezetimibe (82,83). The S-SNEDDS formulation of trans-resveratrol (t-RVT) resulted in the formation of a nanoemulsion, and the pharmacokinetic study indicated that the AUC0-8h of the S-SNEDDS formulation increased by nearly 1.33-fold in the presence of the precipitation inhibitor HPMC (84).…”