應用超臨界溶液快速膨脹法進行藥物Antipyrine、 Benzocaine與4-Dimethylaminoantipyrine之微粒化研究

In this study, RESS process was applied for recrystallization and micronization of three model drugs including antipyrine, benzocaine and 4-dimethylaminoantipyrine. After RESS treatment, the physicochemical properties of the precipitated particles were evaluated by SEM, DSC, FTIR, and XRD analysis. In addition, the dissolution rate studies were conducted to investigate the influence of particle size reduction on the bioavailability of drug. For antipyrine, the particle size was significantly reduced from 35.12 μm to 2.28 μm using RESS method. The processed samples showed narrow size distribution. The variation of some process parameters including extraction temperature, pre-expansion temperature and post-expansion temperature had slight effect on the mean particle size. It was discovered that micronized antipyrine did not revealed noticeable enhancement on the dissolution profile. After RESS process, benzocaine particles were successfully micronized from original size of 153.33 μm to around 3 μm with much narrower size distribution. The effect of pre-expansion temperature, post-expansion temperature and nozzle diameter on the mean particle size and size distribution was studied; and slight influence was noticeable. Dissolution studies showed that dissolution rate of processed particles was enhanced by 2.44 times with new dissolution profile. The untreated 4-dimethylaminoantipyrine was large in size with very wide size distribution ranging from 22 μm to 2468 μm. With RESS treatment, the mean particle size of the drugs was drastically reduced to submicron size, in the range of 1.92 to 7.64 μm. Furthermore, very uniform and narrow size distribution was obtained after RESS micronization. Several operating parameters including pre-expansion temperature, post-expansion temperature and nozzle diameter were investigated. It was proved that pre-expansion temperature and post-expansion temperature have significant effect on the mean particle size, size distribution and morphology. In addition, DSC and XRD results showed that there was polymorphic transformation during RESS process. From dissolution rate study, the results demonstrated that higher dissolution efficiency (enhance degree = 4.37) was obtained as a consequence of significant particle size reduction.