Micronization and Polymorphic Conversion of Tolbutamide and Barbital by Rapid Expansion of Supercritical Solutions
Micronization and Polymorphic Conversion of Tolbutamide and Barbital by Rapid Expansion of Supercritical Solutions
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DOI：
10.1080/03639040500529994
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发表时间：
2006-01
影响因子：
3.4
通讯作者：
H. Shinozaki;T. Oguchi;Shogo Suzuki;K. Aoki;T. Sako;S. Morishita;Y. Tozuka;K. Moribe;Keiji Yamamoto
中科院分区：
文献类型：
--
作者：
H. Shinozaki;T. Oguchi;Shogo Suzuki;K. Aoki;T. Sako;S. Morishita;Y. Tozuka;K. Moribe;Keiji Yamamoto
摘要将超临界溶液快速膨胀（RESS）应用于甲苯磺丁脲和巴比妥。通过测定超临界CO2中的溶解度，可以用简单的方法粗略估计萃取效率，并通过直接分光光度法准确估计萃取效率。后者揭示了甲苯磺丁脲的溶解度是所施加的压力和温度的函数，并且与压力成正比。甲苯磺丁脲的多晶型I和II之间的溶解度没有检测到显著差异。通过粒径分布测定、晶型鉴定和形态学评价对RESS法制备的甲苯磺丁脲和巴比妥颗粒进行了表征。实现了显著的尺寸减小到微米或亚微米级，具有窄的尺寸分布，而常规机械研磨仅具有轻微的效果。颗粒大小受萃取和膨胀条件的影响很大。提取温度越低，平均粒径越小。在相同的提取温度下，较高的提取压力导致较小的平均粒径。通过降低喷嘴温度、通过降低膨胀室温度、通过增加每次喷雾的CO2量以及通过增加废气流速来减小平均粒径。RESS处理也实现了多态转换。至于甲苯磺丁脲，通过改变提取条件，可以产生四种多晶型物中的三种多晶型物（I型、II型和IV型），而在巴比妥的情况下，始终产生三种多晶型物中的一种多晶型物（II型）。
ABSTRACT Rapid expansion of supercritical solutions (RESS) was applied to tolbutamide and barbital. The solubility in supercritical CO2 was determined to estimate the extraction efficiency roughly by a simple method and accurately by a direct spectrophotometric technique. The latter revealed that the solubility of tolbutamide was a function of applied pressure and temperature and was proportional to the pressure. No significant difference in solubility between polymorphic Forms I and II of tolbutamide was detected. Tolbutamide and barbital particles produced by the RESS were characterized by size distribution measurement, polymorph identification and morphological evaluation. Significant size reduction to micron or sub-micron level with narrow size distribution was achieved, while conventional mechanical grinding had only slight effect. The particle size was greatly affected by both extraction and expansion conditions. The lower the extraction temperature was, the smaller was the mean particle size. Higher extraction pressure resulted in smaller mean particle size when compared at the same extraction temperature. The mean particle size was reduced by lowering the spray nozzle temperature, by lowering the expansion chamber temperature, by increasing the CO2 amount per spray, and by increasing the exhaust gas flow rate. The RESS processing realized the polymorphic conversion as well. As for tolbutamide, three polymorphs (Forms I, II, and IV) out of four could be produced by changing the extraction conditions, and in the case of barbital, one polymorph (Form II) out of three was produced consistently.