Nassim Belkacem¹ , Mutaz Sheikh Salem², Hatim Alkhatib³, Chiraz Soumia Amrine⁴

Abstract

Purpose: To investigate the effect of melt-sonocrystallization technique (MS) on the physicochemical characteristics and dissolution of a poorly soluble drug (ketoprofen). Methods: Ketoprofen was heated in paraffin oil bath at 97 °C and then poured into a beaker containing 25 mL deionized water at 25 oC and immediately treated using a probe ultrasonicator at different ultrasonic times, and varying amplitudes at frequency of 20 KHz. Prepared suspensions were evaluated for the effect of temperature and energy of production. Powders were characterized using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infra-red spectrophotometry (FTIR). The Heckle plot, Carr's compressibility index, and Hausner's ratio were used to determine compressibility properties. Furthermore, the angle of slide was used to evaluate flow characteristics. Results: There was a significant reduction in particle size characteristics following melt-sonocrystallization (p < 0.05). The SEM micrographs revealed needle-shaped particles with smooth surfaces. There was no significant difference in DSC thermograms with peaks ranging from 97.3 to 98.1 °C (p < 0.05). The FT-IR spectra showed two specific sharp and symmetrical peaks at (1654.5 cm-1 ) and (1697.3 cm-1 ). Also, distinctive peaks of ketoprofen remained detectable in XRD patterns, indicating that the substance had not undergone structural modification. The solubility increased by 15 %. There was no improvement in flowability or compressibility. Dissolution was greatly improved from 67 to 85 %. Conclusion: Melt-sonocrystallization reduces particle size, solubility, and dissolution with no structural modification to ketoprofen. In vivo investigation of drug bioavailability from the generated powders would be required.