Bioavailability Enhancement and Food Effect Elimination of Abiraterone Acetate by Encapsulation in Surfactant-Enriched Oil Marbles
| Autor: | Jaroslava Roušarová, Ondřej Dammer, Tereza Boleslavská, Josef Beranek, Ondřej Slanař, Petr Kozlík, Martin Krov, Pavel Žvátora, Ondřej Rychecký, Jana Hořínková, František Štěpánek, Tomáš Křížek, Pavel Ryšánek, Martin Šíma, Nikolina Kutinová Canová |
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| Rok vydání: | 2020 |
| Předmět: |
Drug
Male media_common.quotation_subject Drug Compounding Cmax Abiraterone Acetate Pharmaceutical Science Administration Oral Biological Availability Bioequivalence 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound Food-Drug Interactions Surface-Active Agents 0302 clinical medicine Pulmonary surfactant In vivo Animals media_common FOOD EFFECT Chromatography Abiraterone acetate Fasting Postprandial Period Bioavailability Rats Drug Liberation chemistry 030220 oncology & carcinogenesis Area Under Curve Models Animal Pharmaceutical Vehicles Oils |
| Zdroj: | The AAPS journal. 22(6) |
| ISSN: | 1550-7416 |
| Popis: | 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 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 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. |
| Databáze: | OpenAIRE |
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