Oral Bioavailability Study of Olaparib Amorphous Solid Dispersion Prepared by Hot-Melt Extrusion Process

Objective: Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor widely used for the treatment of Breast Cancer gene (BRCA) mutated ovarian, breast, pancreatic, and prostate cancers. However, its oral therapeutic efficacy is limited by poor aqueous solubility and low intestinal permeability, resulting in reduced bioavailability. The present study aimed to develop an amorphous solid dispersion (ASD) of Olaparib using hot-melt extrusion (HME) technology to improve its oral bioavailability. Methods: The ASD of Olaparib was prepared using HME with polyvinylpyrrolidone (PVP K30) as the carrier polymer. The optimized formulation was evaluated through an in vivo pharmacokinetic study in Wistar rats. Pure Olaparib and the optimized ASD formulation were administered orally at an equivalent dose of 4 mg/kg body weight. Plasma samples were collected at predetermined time intervals and analyzed using a validated high-performance liquid chromatography (HPLC) method employing a Phenomenex Luna® C8 column with a mobile phase consisting of Methanol and Acetonitrile (70:30, v/v). Results: The optimized ASD formulation showed a marked improvement in plasma drug concentration compared with pure Olaparib. The maximum plasma concentration (Cₘₐₓ) increased from 115.00±4.25 ng/ml for pure Olaparib to 180.00±3.20 ng/ml for the optimized ASD, while Tₘₐₓ remained 6 h for both formulations. The optimized formulation also confirms higher AUC0–30 (2730.65 ng·h/ml) and Area under the plasma concentration–time curve from time zero to infinity (AUC₀–∞) (2843.08ng·h/ml) compared with pure Olaparib (1731.53±85.42 and 1817.19±90.10 ng·h/ml, respectively), resulting in an approximate 156.45% relative oral bioavailability. Conclusion: The HME-based ASD of Olaparib enhanced its oral bioavailability by improving systemic drug exposure. These findings suggest that the optimized ASD formulation is a promising approach for overcoming the poor biopharmaceutical properties of Olaparib and may improve its oral therapeutic performance.