In vitro dissolution methods correctly predicting in vivo bioavailability of compounds from complex mixtures are lacking. We therefore used data on the in vivo performance of bioavailability-improved curcumin formulations to implement an in vivo predictive dissolution method (BiPHa+). BiPHa+ was applied for the characterization of eight curcumin formulations previously studied in a strictly controlled pharmacokinetic human trial. During dissolution, the dissolved proportion of curcumin in the aqueous medium underwent a formulation-dependent reduction, whereas the proportion remained stable in the organic layer. Compared with conventional dissolution systems, BiPHa+ was superior in terms of in vivo-relevant formulation characterization. All formulations could be precisely categorized according to their bioavailability in humans. In vitro-in vivo relationships for each dissolution method were established, with BiPHa+ providing the highest degree of linearity (r2 = 0.9975). The BiPHa+ assay correctly predicted the bioavailability of curcuminoids from complex mixtures and provided mechanistic information about formulation-dependent release characteristics.
Keywords: bioavailability; biphasic dissolution; curcumin formulations; in vitro–in vivo relationship; pharmacokinetics.