Abiraterone acetate is a potent drug used for the treatment of metastatic castration resistant prostate cancer. However, currently marketed product containing crystalline abiraterone acetate exhibits strong positive food effect which results in strict dosing regimen. In the present work, a rational approach towards design of novel abiraterone acetate formulations that would allow increased bioavailability on a fasting stomach and thus decreased food effect is presented. Precipitation experiments in biorelevant media were designed to assess pH induced precipitation of the drug and a pool of polymeric excipients was then screened for their potential to inhibit precipitation. The best performing polymeric excipients were subsequently used as carriers for the preparation of amorphous solid dispersions. Two main approaches were followed in order to formulate the drug. The first approach relies on the suppression of precipitation from a supersaturated solution whereas the second one is based on the hypothesis that when the release of the drug is tuned, optimal uptake of the drug can be reached. Optimized formulation prototypes were tested in a rat animal model in an incomplete block, randomized bioequivalence study to assess their relative bioavailability under fasting conditions. We show that both formulation approaches lead to increased bioavailability of abiraterone acetate on a fasting stomach with bioavailability in rats being enhanced up to 250% compared to the original drug product containing crystalline drug.

Department of Analytical Chemistry Faculty of Science Charles University Prague Czech Republic

Department of Chemical Engineering University of Chemistry and Technology Prague Technická 5 166 28 Prague Czech Republic

Institute of Pharmacology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Zentiva k s U Kabelovny 130 102 37 Prague Czech Republic

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

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