Development of Abiraterone Acetate Nanocrystal Tablets to Enhance Oral Bioavailability: Formulation Optimization, Characterization, In Vitro Dissolution and Pharmacokinetic Evaluation

Abstract

Abiraterone acetate is a prodrug of abiraterone used in combination with prednisone as a standard therapeutic strategy for hormone-resistant prostate cancer (mCRPC). Due to the poor solubility and permeability, the release and absorption of abiraterone acetate are low and reduce its bioavailability. In this project, abiraterone acetate tablets prepared using nanocrystal technology were developed to overcome the drawbacks of normal tablets by enhancing in vitro dissolution rate and oral bioavailability. The abiraterone acetate nanocrystal suspensions were prepared by top-down wet milling method using a planetary ball mill with the mixture of Poloxamer 407 and Poloxamer 188 as the optimized stabilizer at a ratio of 7:1. The optimized nanocrystals were freeze-dried and characterized using DLS, TEM, DSC, and XRD. The abiraterone acetate nanocrystal tablets significantly improve the in vitro dissolution rate of abiraterone acetate compared to raw materials. Although exhibiting a similar dissolution rate compared to the Zytiga® tablets, the nanocrystal tablets significantly improve the oral bioavailability with Cmax and AUC0–t being 3.51-fold and 2.80-fold higher, respectively, in the pharmacokinetic study. The present data indicate that nanocrystal is a promising strategy for improving the dissolution and bioavailability of abiraterone acetate.

A Scalable Freeze-Dissolving Approach to Prepare Ultrafine Crystals for Inhalation: Mechanism and Validation

“…Furthermore, the preparation strategy was validated for a broader range of model drugs including nifedipine (NFD), fenofibrate (FNB), and vinpocetine (VNT) for the treatment of cardiovascular and other related diseases. − Additionally, abiraterone acetate (AAC) and curcumin (CUR), known for their anticancer or anti-inflammatory effects, , as well as itraconazole (ITZ) used in the therapy of systemic fungal infections were also included . The operating parameters can be flexibly designed to enhance the product quality or micropowder preparation efficiency.…”

Optimizing Abiraterone Delivery through Intratumoral In Situ Implant: A Prospective Pharmaceutical Development Approach

“…However, Yuanfen Liu et al (34) created nanocrystalline tablets of abiraterone acetate, which increased oral bioavailability. This dosage form is obtained by the dry granulation method, where freeze-dried nanocrystals, fillers, stabilizers, and disintegrants are precisely weighed, mixed, and then compressed into flakes.…”

Synthesis and Biological Evaluation of Methoxypolyethylene-Glycol-Substituted Abiraterone Derivatives as Potential Antiprostate Cancer Agents

“…Studies have focused on the development of novel formulations to improve Abi bioavailability. ,, Liu et al used nanocrystal technology to develop tablets and increased the dissolution rate of AbA, which improved the oral bioavailability with C max and AUC 0–t being 3.51-fold and 2.80-fold compared to the Zytiga tablets . Schultz et al formulated a supersaturated silica–lipid hybrid (SLH), typically used to increase the oral bioavailability of lipophilic medicines with poor water solubility, to enhance the solubilization and oral bioavailability of AbA. , Compared to the unformulated AbA and Zytiga tablets, SLH (90% S eq ) increased 31-fold and 1.43-fold in the oral bioavailability while super-SLH P enhanced 16–19-fold and 2–2.5-fold in AbA solubilization, respectively.…”