Formation of Ketoprofen-Malonic Acid Cocrystal by Solvent Evaporation Method

Yudi Wicaksono(1*), Dwi Setyawan(2), Siswandono Siswandono(3)

(1) Faculty of Pharmacy, University of Jember Center for Development of Advanced Science and Technology, University of Jember
(2) Faculty of Pharmacy, Airlangga University
(3) Faculty of Pharmacy, Airlangga University
(*) Corresponding Author


The purpose of this work was to explore the formation of ketoprofen-malonic acid cocrystal by solvent evaporation method. Early detection of cocrystal formation was conducted by hot stage microscopy and solid-liquid phase diagram. Cocrystal were prepared by solvent evaporation method by using isopropyl alcohol as solvent. Characterization of cocrystal was done by Powder X-Ray Diffractometry (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) Spectroscopy and Scanning Electron Microscopy (SEM). The results of hot stage microscopic and solid-liquid phase diagram indicated formation of ketoprofen-malonic acid cocrystal. PXRD and DSC measurements showed stoichiometric ratio of cocrystal ketoprofen-malonic acid (2:1). The ketoprofen-malonic acid cocrystal had melting point at 86.2 °C and unique peaks of PXRD pattern at 2θ of 6.1°, 17.8°, 23.2° and 28.6°. FTIR spectra indicated the formation of cocrystal due to interaction of C=O ketone group of ketoprofen with MA molecule. SEM images show that ketoprofen-malonic acid cocrystal have multi-shaped particles with rough surfaces.


ketoprofen; cocrystal; hot stage microscopy; solid-liquid phase diagram

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