Bioavailability Enhancement and Food Effect Elimination of Abiraterone Acetate by Encapsulation in Surfactant-Enriched Oil Marbles

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 C 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.

Open-Label, Phase I, Pharmacokinetic Studies in Healthy Chinese Subjects to Evaluate the Bioequivalence and Food Effect of a Novel Formulation of Abiraterone Acetate Tablets

“…5 Abiraterone acetate is a Biopharmaceutics Classification System class IV compound, with an extremely low oral bioavailability when administered in the fasted state. 6 However, the administration of abiraterone acetate with highfat food results in up to a 10-fold increased area under the concentration-time curve (AUC) and up to a 17-fold increase in the maximum plasma concentration (C max ) of abiraterone. 7 Because of the low oral bioavailability and significant food effect of abiraterone acetate, its administration carries a risk of toxicity and inaccurate dosing.…”

Validity of cycloheximide chylomicron flow blocking method for the evaluation of lymphatic transport of drugs

“…Two separate two‐period, one sequence, crossover studies were conducted to compare the bioavailability of either abiraterone capsule or cinacalcet oil solution after oral dosing with and without pre‐treatment with chylomicron flow blocking agent cycloheximide. The crossover study design in rats was chosen and conducted as described previously (Boleslavská, Rychecký, et al, 2020). Both studies were conducted similarly.…”

“…The crossover study design in rats was chosen and conducted as described previously (Boleslavská, Rychecký, et al, 2020). Both studies were conducted similarly.…”

Green liquid marble-based hydrogels as pesticidal pyrethrin slow-release carriers

“…28 Owing to these properties, such as easy preparation, wide source of raw materials, non-wetting and good elasticity, liquid marbles have gained increasing attention and are widely used in fields of cosmetics, microfluidics, microreactors and biopharmaceuticals. [29][30][31][32][33][34] However, limited by their poor mechanical stability, up to now, liquid marbles have rarely been used in the agriculture sector to release pesticide. 35 Herein, the advantages of liquid marbles and the habit of mosquito larvae were exploited, using green substances, such as cellulose, sodium alginate and gelatin, to design a hydrogel drug carrier to kill Aedes albopictus larvae continuously and chronically with fewer doses (Scheme 1).…”

“…28 Owing to these properties, such as easy preparation, wide source of raw materials, non-wetting and good elasticity, liquid marbles have gained increasing attention and are widely used in fields of cosmetics, microfluidics, microreactors and biopharmaceuticals. 29–34 However, limited by their poor mechanical stability, up to now, liquid marbles have rarely been used in the agriculture sector to release pesticide. 35…”