In vivo predictive dissolution of the lipophilic phytochemicals trans-resveratrol, coenzyme Q10 and quercetin

Abstract

Biphasic dissolution consisting of an aqueous dissolution and an overlaying organic distribution compartment, is an innovative screening approach for the oral bioavailability of pharmacologically active compounds. As in vivo-relevant dissolution methods predicting the in vivo bioavailability of compounds from natural extracts are lacking, we sought to establish and validate an in vivo predictive in vitro biphasic dissolution method (BiPHa+) using human pharmacokinetic data from oral formulations of trans-resveratrol, coenzyme Q10 (CoQ10) and quercetin (including a grapevine-shoot extract, micellar formulations, a water-dispersible formulation with reduced recrystallization, an oily dispersion and phytosomes). The formulations were characterized using the BiPHa+ and compared to conventional monophasic dissolution methods. The comparison emphasized the advantages of the BiPHa+ in terms of powerful correlation. In case of resveratrol and CoQ10, only the combination of aqueous non-sink dissolution with an organic absorption sink enabled the differentiation of formulations and their in vivo-relevant characterization. In particular, the expected bioavailability of micellar formulations cannot be estimated solely based on their water solubility. Concerning the quercetin formulations biphasic dissolution was not essential, but advantageous. Based on the obtained results, the BiPHa + can be applied not only for characterization of different formulations but also to natural products with different physicochemical properties, such as water solubility and lipophilicity.