Resveratrol Supported on Magnesium DiHydroxide (Resv@MDH) Represents an Oral Formulation of Resveratrol With Better Gastric Absorption and Bioavailability Respect to Pure Resveratrol

Rossana Giulietta Iannitti; Alessandro Floridi; Andrea Lazzarini; Alice Tantucci; Roberta Russo; Francesco Ragonese; Lorenzo Monarca; Concetta Caglioti; Roberto Spogli; Lucio Leonardi; Massimiliano De Angelis; Federico Palazzetti; Bernard Fioretti

doi:10.3389/fnut.2020.570047

Resveratrol Supported on Magnesium DiHydroxide (Resv@MDH) Represents an Oral Formulation of Resveratrol With Better Gastric Absorption and Bioavailability Respect to Pure Resveratrol

Front Nutr. 2020 Nov 13:7:570047. doi: 10.3389/fnut.2020.570047. eCollection 2020.

Affiliations

¹ S&R Farmaceutici S.p.A., Perugia, Italy.
² Forensic Toxicology Laboratory, CRABioN Research Center, Perugia, Italy.
³ Department of Medicine, University of Perugia, Perugia, Italy.
⁴ Department of Chemistry, Biology, and Biotechnologies, University of Perugia, Perugia, Italy.
⁵ Prolabin & Tefarm, Spin-Off Un. of University of Perugia, Perugia, Italy.

Abstract

Resveratrol attracts great interest because of the plethora of in vitro effects at the micromolar concentration range. Unfortunately, these effects are difficult to establish in vivo, due to the low concentration of resveratrol reached. This discrepancy is due to the molecules low solubility in water that favors the propensity for an intestinal absorption rather than in the gastric compartment. To address these challenges, we developed a Solid Dispersion of Resveratrol Supported by Magnesium Di Hydroxide formulation (Resv@MDH). This formulation displays increased water solubility and better bioavailability relative to pure resveratrol in the rabbit animal model. In our study, we evaluated the pharmacokinetics profile of resveratrol in six healthy human subjects following 180 mg of oral resveratrol administration, derived from Resv@MDH or pure resveratrol. Free resveratrol was evaluated in the whole blood sample by using HPLC - MS/MS. In comparison with pure resveratrol that displays an increase of the maximum plasma concentration, Cmax at about 90 min and 2 μM, Resv@MDH displays an earlier peak of resveratrol concentration with an increase of Cmax at about 30 min and 6 μM. The different kinetics suggest a main gastric route for resveratrol absorption from Resv@MDH, where, because of its improved dissolution rate, there seems to be a higher propensity for an acidic environment, as opposed to that with pure resveratrol. This conclusion is also supported by the numerical simulation analysis, which considers the principal steps during the oral route administration. Moreover, there is a 2-fold increase in the amount of free resveratrol with respect to pure resveratrol confirming a better bioavailability observed in the animal model. The characteristic feature of the pharmacokinetic profile of Resv@MDH implies that the beneficial properties of resveratrol in human health should be capitalized on it.

Keywords: bioavailability; dissolution rate; human health; resveratrol; whole blood concentration.