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

Aris Purwanto; Arisah Dama Yanti; Yesi Tera Insani; Nurul Mahfuzatun Nisa; Ainun Jariyah; Heri Wijaya

doi:10.31632/ijalsr.2025.v08i03.006

Aris Purwanto Faculty of Pharmacy, Universitas Muhammadiyah Banjarmasin, Jln. Gubernur Sarkawi, Handil Bakti, South Kalimantan, Indonesia https://orcid.org/0009-0000-6890-8662
Arisah Dama Yanti Faculty of Pharmacy, Universitas Muhammadiyah Banjarmasin, Jln. Gubernur Sarkawi, Handil Bakti, South Kalimantan, Indonesia https://orcid.org/0009-0000-0386-5876
Yesi Tera Insani Faculty of Pharmacy, Universitas Muhammadiyah Banjarmasin, Jln. Gubernur Sarkawi, Handil Bakti, South Kalimantan, Indonesia https://orcid.org/0009-0009-5647-8306
Nurul Mahfuzatun Nisa Faculty of Pharmacy, Universitas Muhammadiyah Banjarmasin, Jln. Gubernur Sarkawi, Handil Bakti, South Kalimantan, Indonesia https://orcid.org/0009-0002-6865-3465
Ainun Jariyah Faculty of Pharmacy, Universitas Muhammadiyah Banjarmasin, Jln. Gubernur Sarkawi, Handil Bakti, South Kalimantan, Indonesia https://orcid.org/0009-0001-3254-741X
Heri Wijaya Faculty of Pharmacy, Sekolah Tinggi Ilmu Kesehatan Samarinda, A.W. Syahranie, East Borneo, 75124, Indonesia https://orcid.org/0000-0002-6056-8699

DOI https://doi.org/10.31632/ijalsr.2025.v08i03.006

Abstract

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.

Keywords: Absorption, Cholesterol, Ezetimibe Co-Crystal, Solvent Drop Grinding Ezetimibe

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