Bioavailability Enhancement and Food Effect Elimination of Abiraterone Acetate by Encapsulation in Surfactant-Enriched O
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Research Article Bioavailability Enhancement and Food Effect Elimination of Abiraterone Acetate by Encapsulation in Surfactant-Enriched Oil Marbles Tereza Boleslavská,1,2 Ondřej Rychecký,1,2 Martin Krov,2 Pavel Žvátora,1 Ondřej Dammer,1 Josef Beránek,1 Petr Kozlík,3 Tomáš Křížek,3 Jana Hořínková,4 Pavel Ryšánek,4 Jaroslava Roušarová,4 Nikolina Kutinová Canová,4 Martin Šíma,4 Ondřej Slanař,4 and František Štěpánek2,5 Received 29 June 2020; accepted 27 August 2020 Abstract. 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 by in vitro and in vivo experiments that the food effect can be suppressed. OMs are spherical particles with a core-shell structure, formed by coating oilbased 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 during in vitro experiments when compared with originally marketed formulation of abiraterone acetate (Zytiga®). Based on in vitro comparison of OMs containing different oil/surfactant combinations, the most promising formulation was chosen for in vivo studies. To ensure relevance, it was verified that the food effect previously reported for Zytiga® 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 of Cmax. 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. KEY WORDS: bioavailability; bioequivalence; food effect; formulation; liquid marble.
INTRODUCTION
Tereza Boleslavská and Ondřej Rychecký contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1208/s12248-020-00505-5) contains supplementary material, which is available to authorized users. 1
Zentiva, k.s., U Kabelovny 130, 102 37, Prague, Czech Republic. Department of Chemical Engineering, University of Chemistry and Technology, Prague, Technická 5, 166 28, Prague, Czech Republic. 3 Department of Analytical Chemistry, Faculty of Science, Charles University, Prague, Czech Republic. 4 Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. 5 To whom correspondence should be addressed. (e–mail: [email protected]) Abbreviations: API, active pharmaceutical ingredient; ASD, amorphous solid dispersions; AUC, area under the curve; ODP, original drug
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