Microparticle Production of Mefenamic Acid Using the Continuous Antisolvent Sonocrystallization Process

Continuous crystallizations have promising potential for effectively controlling and modifying the crystal properties of active pharmaceutical ingredients (APIs). In this study, a continuous antisolvent sonocrystallization process was developed to recrystallize a poorly water-soluble API, mefenamic acid, for microparticle production. This method offers advantages such as efficient sonication, enhanced heat removal, and potential for scalability. The effects of operating parameters, such as sonication intensity, crystallization temperature, antisolvent flow rate, and solution flow rate, were investigated and compared. Using continuous antisolvent sonocrystallization, the particle size of mefenamic acid was controlled within the range of 2.6–3.5 μm, achieving a narrower particle size distribution compared to the unprocessed sample. In addition, scanning electron microscopy (SEM) analysis confirmed that the sonocrystallized mefenamic acid exhibited an improved crystal shape. Analytical results from powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) showed that the crystal structure, spectroscopic characteristics, and thermal behavior of mefenamic acid remained unchanged after the sonocrystallization process.