In vitro and in vivo performance of amorphous solid dispersions of ursolic acid as a function of polymer type and excipient addition.

Abstract

Objectives: The objective of this research was to enhance the bioavailability of ursolic acid (UA) by preparing multielement amorphous solid dispersion (ASD) systems comprising excipients.

Methods: The ASDs were prepared via the solvent evaporation method, characterized by a range of techniques, and investigated with respect to permeability of human colorectal adenocarcinoma cell line (Caco-2) cells monolayers and pharmacokinetics, with comparisons made to the physical mixture and the pure drug.

Key findings: The (UA-choline)-Polyethylcaprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer (Soluplus)-Vitamin E polyethylene glycol succinate (TPGS) ASD demonstrated superior dissolution properties compared to the corresponding binary solid dispersions and ternary solid dispersions (P < .05). The permeability studies of Caco-2 cell monolayers revealed that the ASD exhibited moderate permeability, with an efflux rate that was significantly lower than that of the UA raw material (P < .05). Pharmacokinetic studies in rats demonstrated that the oral bioavailability of the ASD was 19.0 times higher than that of UA (P < .01).

Conclusions: The research indicated that the multielement ASD could be employed as an efficacious drug delivery system for UA. Furthermore, the Soluplus/TPGS/choline combination represents a promising candidate for the fabrication of ASDs that can load weakly acidic and poorly soluble drugs.