Development of abiraterone acetate tablets with enhanced oral bioavailability

Abiraterone acetate (ABA), a precursor drug inhibiting androgen biosynthesis (CYP17 inhibitor), is used for treating metastatic castration-resistant prostate cancers. However, it falls under the Biopharmaceutical Classification System Class IV due to low solubility and permeability. This study aims to reduce its daily dose through formulation optimization, focusing on improving solubility, dissolution, and oral bioavailability.

Various methods, such as air-jet milling, solid dispersion through spray drying, inclusion complex formation with hydroxypropyl-β-cyclodextrin, were explored to increase the solubility of ABA. Additionally, we formulated a tablet formulation with reduced total weight compared to the marketed product. Finally, we conducted a pharmacokinetic study to assess the profiles of the optimized ABA formulation in beagle dogs.

All tested methods resulted in an increased aqueous solubility of ABA. Notably, the complexation of ABA with hydroxypropyl-β-cyclodextrin exhibited the most significant enhancement in solubility. Also, it was important for the dissolution that the amount of surfactants incorporated in the formulations is considered. The final optimized formulation, incorporating hydroxypropyl-β-cyclodextrin and surfactant, ensured dissolution equivalence under in vitro conditions. Moreover, it demonstrated bioequivalence to the marketed product, exhibiting similar pharmacokinetic parameters such as AUC, C_max, and T_max.

The ABA tablet was successfully developed to enhance the solubility of ABA. It was smaller in tablet size than the marketed product but still bioequivalent, which may improve the convenience of administration and patients’ compliance.