Study of the RESS Process for Micronization of Clofibric acid and Thymol

• Main Authors: Hao-Chih Chien, 簡豪志
• Other Authors: Yan-Ping Chen
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/77726420477263782323

碩士 === 國立臺灣大學 === 化學工程學研究所 === 104 === In this study, RESS process was applied for micronization and recrystallization of two active pharmaceutical ingredients (APIs) including clofibric acid and thymol. Also, Taguchi Method has been used to design for the experiment. Taguchi’s parameter design is an important tool for robust design. It offers a simple and systematic approach to optimize design for performance, quality and cost. After RESS processed, the submicron particles were precipitated in the expansion vessel with various effects of operating factors like extraction temperature (Text), extraction pressure (Pext), post temperature (Tpost), and the nozzle diameter (DN). Then, the original and micronized APIs were evaluated by SEM, FTIR, DSC, XRD and TGA analysis. Moreover, the comparison of the dissolution profile between original and RESS-processed APIs was also shown in this study. For clofibric acid, the particle size was dramatically reduced from 97.41 μm to 1.01 μm by RESS process. There was no change of the physical and chemical properties after the RESS process. Also, the decrease of crystallinity can be observed in the XRD result. Results from Taguchi method and analysis of variance (ANOVA) showed that nozzle diameter was the most significant factor. Then, the dissolution rate constant (kw) of original and RESS-processed particles can be calculated by optimally fitting the data points with Weibull model. As a result, the rate of dissolution only enhanced 1.85 times. Similar result can be discovered in the API thymol through RESS process. The mean particle size was significantly micronized from 1385.21 μm to 21.35 μm. Although no polymorphic transformation was found, the crystallinity of RESS-processed thymol diminished. Besides, the physical and chemical properties of the thymol remained the same. Results from Taguchi method and analysis of variance (ANOVA) showed that post-expansion temperature was the most important factor. Dissolution studies reported that the dissolution rate improved 4.42 times.