Molecular Encapsulation of Abiraterone Acetate in 2,6 Di-O-Methyl-β-Cyclodextrin for Solubility Enhancement: Synthesis, Characterization, In Vitro Drug Release, and Molecular Docking

This study endeavors to augment the aqueous solubility and dissolution profile of abiraterone acetate (ABT) through the strategic establishment of inclusion complexes with 2,6 Di-O-methyl β-cyclodextrin (DM-β-CD). Phase solubility assessments of ABT, conducted in an aqueous phase at room temperature, illuminated the impact of DM-β-CD on its solubility. Subsequently, an inclusion complex was meticulously fabricated via the solvent evaporation method. The resultant ABT-DM-β-CD inclusion complex (IC) underwent rigorous evaluation encompassing aqueous saturation solubility studies, determination of drug loading, and estimation of entrapment efficiency. The establishment of the IC was further substantiated through an array of analytical techniques, including molecular docking, Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H-NMR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), contact angle and in vitro dissolution studies. ABT-DM-β-CD IC was formed in a 1:1 stoichiometric ratio, resulting in substantial increase in aqueous solubility by ~ 137.51-fold. Results unveiled encapsulation efficiency and drug loading of ABT-DM-β-CD IC 90.40 ± 0.60% and 20.55 ± 0.14%, respectively. Chemical interaction through FTIR and ¹H-NMR revealed the complexation occurred between ABT and DM-β-CD. Solid-state analyses indicated drug amorphization within the IC, consequentially amplifies drug solubility. The solubility profile of ABT and its IC demonstrated a remarkable enhancement in aqueous solubility, attributed to the inherent hydrophilicity of DM-β-CD. These findings underscore the potential for further investigation in the formulation and development of drug carriers tailored for the delivery of hydrophobic drugs.