Investigating the Role of Phenolic Acid Coformers in Enhancing the Physicochemical Properties of Enzalutamide Coamorphous Systems

Coamorphous systems are gaining interest as an effective formulation strategy to improve the solubility and dissolution of poorly water-soluble drugs. This study investigates the role of phenolic acids as coformers in enhancing the physicochemical properties of enzalutamide (ENZ), a poorly soluble anticancer drug. Five phenolic acids-p-coumaric acid (CMA), ferulic acid (FRA), cinnamic acid (CNA), vanillic acid (VNA), and p-hydroxybenzoic acid (HBA)-were selected based on their glass-forming ability and potential for molecular interactions. Coamorphous systems were prepared and characterized using powder X-ray diffraction (PXRD), modulated differential scanning calorimetry (mDSC), attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), and Raman spectroscopy. All coformers successfully induced amorphization, evidenced by halo patterns in PXRD and single glass transition temperatures in mDSC. Spectroscopic analysis confirmed the absence of strong intermolecular bonding, indicating homogeneous mixing. The coamorphous systems exhibited improved solubility across physiological pH conditions and maintained supersaturation for at least four hours under non-sink dissolution testing. These results highlight the potential of phenolic acids as coformers in developing stable, high-performing coamorphous drug systems to enhance the bioavailability of poorly soluble APIs like enzalutamide.