Investigation of process parameters by using a two-level factorial design for microparticle production of ipriflavone through rapid expansion of supercritical solution process

Abstract This study investigated the significance of process parameters in the rapid expansion of supercritical solutions (RESS) for microparticle production of ipriflavone by using a two-level (2k) factorial design. Four process parameters, namely the extraction temperature (A), extraction pressure (B), pre-expansion temperature (C), and postexpansion temperature (D), of RESS were studied. The mean particle size data and results of analysis of variance revealed that the effect of C and the cross-interaction effect of AD and BD were significant in the process. The trends of these significant effects were evaluated through crystallization kinetics. After the RESS was performed, ipriflavone exhibited a considerably reduced mean size of 3 μm and a flake-like habit. In addition, differential scanning calorimetry and powder X-ray diffraction revealed that the crystal form of ipriflavone remained unchanged after RESS.