Enhancing Ezetimibe Absorption: Formation and Characterization of Drug Cocrystals with Carboxylic Acid Coformers

Background: Ezetimibe (EZT) is a newer FDA-approved drug that inhibits cholesterol absorption in the intestines without affecting the uptake of fat-soluble vitamins. However, EZT is classified under the Biopharmaceutics Classification System (BCS) as a Class II drug, characterised by low solubility and limited absorption. Objective: This study aims to enhance the solubility and bioavailability of EZT through cocrystallisation with carboxylic acid coformers. Methods: Cocrystals were prepared using the solvent-drop grinding technique. Characterisation was performed using Particle Size Analysis (PSA), Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and dissolution testing. Results: The EZT cocrystals exhibited a smaller particle size (0.728 µm) compared to pure EZT (1.049 µm), and PXRD analysis confirmed the formation of a new crystalline phase. DSC results showed a reduced melting point for the cocrystal (76.99°C) compared to pure EZT (81.54°C), while FTIR spectra indicated the formation of hydrogen bonds. SEM images revealed that the cocrystals had a more fragmented and rougher morphology compared to the smoother particles of pure EZT. Dissolution testing demonstrated enhanced solubility, with 49.13% of the EZT cocrystal dissolved at 15 minutes versus 13.90% for pure EZT, indicating improved potential for absorption and therapeutic efficacy. Conclusion: The formation of EZT cocrystals significantly enhances the drug’s solubility and absorption, supporting the potential of cocrystallisation as an effective strategy for improving the bioavailability of poorly soluble drugs.