Bioavailability Enhancement and Food Effect Elimination of Abiraterone Acetate by Encapsulation in Surfactant-Enriched Oil Marbles
Abstrakt
Abiraterone acetate has limited bioavailability in the fasted state and exhibits a strong positive food effect. We present a novel formulation concept based on the so-called oil marbles (OMs) and show byin vitroandin vivoexperiments that the food effect can be suppressed.
OMs are spherical particles with a core-shell structure, formed by coating oil-based droplets that contain the dissolved drug by a layer of powder that prevents the cores from sticking and coalescence. OMs prepared in this work contained abiraterone acetate in the amorphous form and showed enhanced dissolution properties duringin vitroexperiments when compared with originally marketed formulation of abiraterone acetate (Zytiga(R)).
Based onin vitrocomparison of OMs containing different oil/surfactant combinations, the most promising formulation was chosen forin vivostudies. To ensure relevance, it was verified that the food effect previously reported for Zytiga(R)in humans was translated into the rat animal model.
The bioavailability of abiraterone acetate formulated in OMs in the fasted state was then found to be enhanced by a factor of 2.7 in terms of AUC and by a factor of 4.0 in terms ofC(max). Crucially, the food effect reported in the literature for other abiraterone acetate formulations was successfully eliminated and OMs showed comparable extent of bioavailability in a fed-fasted study.
Oil marbles therefore seem to be a promising formulation concept not only for abiraterone acetate but potentially also for other poorly soluble drugs that reveal a positive food effect.