Computational and Experimental Approaches for HPMCAS-Based Solid Dispersions of Abiraterone Acetate: Formulation, Characterization, and Biopharmaceutical Enhancement Evaluation.

OBJECTIVE: To enhance the solubility, dissolution rate, and permeability of poorly water-soluble drug Abiraterone Acetate (ABA) by developing solid dispersions using hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF). SIGNIFICANCE: Enhancing the biopharmaceutical performance of ABA is crucial due to its extremely poor solubility and dissolution characteristics. The present study demonstrates that HPMCAS-LF-based solid dispersion effectively improves the physicochemical performance of ABA through enhanced solubility, dissolution, and in vitro drug diffusion. METHODS: Molecular dynamics (MD) simulations were conducted over 100 ns to evaluate the stability and structural behavior of the ABA-HPMCAS-LF complex, with analyses including root mean square deviation (RMSD), radius of gyration and solvent-accessible surface area . Binding free energy was measured using MM-GBSA calculations. Solid dispersions were prepared using co-grinding and solvent assisted cogrinding techniques and characterized by FTIR, PXRD, thermal analysis (TGA/DTG-DTA), SEM, and solid-state13C NMR. Solubility, in vitro dissolution, in vitro drug diffusion, hygroscopicity, and anticancer activity were assessed. RESULTS: The ABA-HPMCAS-LF complex exhibited dynamic stability, with RMSD stabilization at 6-7 Å and a binding free energy of -33.45 kcal/mol, indicating strong van der Waals, lipophilic, and Coulombic interactions. Solid dispersions demonstrated a 1.07 to 16.72-fold increase in solubility compared to pure ABA, and in vitro release enhanced drug dissolution across different media. Diffusion increased by 6.36-fold in simulated gastric fluid (SGF 1.2) and 2.55-fold in phosphate buffer (pH 6.8) relative to pure ABA. CONCLUSION: The solid dispersion of ABA with HPMCAS-LF significantly improved solubility, dissolution, and diffusion, highlighting its potential for enhanced oral bioavailability and improved therapeutic outcomes.