利用超臨界溶液快速膨脹法進行藥物Monobenzone、Ethylparaben、Edaravone與Kojic acid之微粒化研究

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In this study, RESS process was applied for micronization and recrystallization of four active pharmaceutical ingredients (APIs) including monobenzone, ethylparaben, edaravone and kojic acid. After RESS processed, the submicron particles were precipitated in the expansion vessel with various effects of operation parameters like extraction temperature (Text), extraction pressure (Pext), post temperature (Tpost) and the nozzle diameter (DN). And then they were evaluated by SEM, FTIR, DSC, XRD and TGA analysis. In addition, the dissolution profile of RESS-processed particles will be compared to the originals. For monobenzone, the particle size was significantly reduced from 264.69 μm to 0.64 μm by RESS process. We found that there was polymorph transformation occurred of the micronized particles and the decrease of crystallinity after the process. With the Weibull model, the dissolution rate constant (kw) of original and RESS-processed particles were 0.001807 min-1 and 0.002525 min-1, respectively. It showed that the RESS-processed monobenzone had a slight improve on dissolution behavior than the originals. Same results were discovered on the compound ethylparaben through RESS process, the particles were greatly micronized from 933.35 μm to 0.64 μm. In addition to the decrease of the crystalliniy, compound’s polymorph transformation was not change after the RESS process, either. Dissolution studies showed that the dissolution rate constant (kw) promoted from 0.023746 min-1 to 0.439319 min-1 after processed, which meant the dissolution rate of RESS-processed particles was enhanced by 18.5 times with new dissolution profile. For the last two drugs edaravone and kojic acid. Without any metamorphism after RESS processed, they were successfully micronized from their original sizes 36.74 μm and 232.40 μm to around 1.67 μm and 0.31 μm. Through several effects and conditions above, post temperature and nozzle diameter were the two most significant effects on the mean particle size, size distribution and morphology in this study. At last, We also used RESSAS process to form the monobenzone particles in aqueous suspension, the mean particle size was further reduced to 0.11 μm and was 5.8 times smaller than the RESS-processed.