化工学报 ›› 2022, Vol. 73 ›› Issue (10): 4285-4297.DOI: 10.11949/0438-1157.20220468
郑海峰(), 贾晟哲, 王崧成, 韩瑞, 韩丹丹, 高振国(), 龚俊波
收稿日期:
2022-04-01
修回日期:
2022-07-25
出版日期:
2022-10-05
发布日期:
2022-11-02
通讯作者:
高振国
作者简介:
郑海峰(1998—),男,硕士研究生,zhenghf207112@tju.edu.cn
基金资助:
Haifeng ZHENG(), Shengzhe JIA, Songcheng WANG, Rui HAN, Dandan HAN, Zhenguo GAO(), Junbo GONG
Received:
2022-04-01
Revised:
2022-07-25
Online:
2022-10-05
Published:
2022-11-02
Contact:
Zhenguo GAO
摘要:
超细晶体由于其尺寸小、比表面积大等独特性质而被广泛应用于医药、化工等领域。综述了超细晶体的制备方法,以及各种制备方法的原理和粒度控制参数。总结了超细晶体在吸入剂、含能材料以及难溶药物等领域的应用,同时对超细晶体悬浮液的稳定性、颗粒聚结进行了讨论分析,并对超细晶体的发展提出展望。
中图分类号:
郑海峰, 贾晟哲, 王崧成, 韩瑞, 韩丹丹, 高振国, 龚俊波. 超细晶体的研究进展[J]. 化工学报, 2022, 73(10): 4285-4297.
Haifeng ZHENG, Shengzhe JIA, Songcheng WANG, Rui HAN, Dandan HAN, Zhenguo GAO, Junbo GONG. Advances in crystallization of ultrafine crystals[J]. CIESC Journal, 2022, 73(10): 4285-4297.
表1 利用溶析结晶技术制备的超细晶体
Table 1 Ultrafine crystals prepared by antisolvent crystallization technology
溶质/溶剂 | 进料速率/( | 干燥气 | 干燥气速/(m3/h) | 产品粒径/μm | 文献 |
---|---|---|---|---|---|
[ | |||||
黑索今/丙酮 | 空气 | — | 0.4~0.6 | [ | |
[ | |||||
奥克托今/丙酮 | 10 | 35 | 1 | [ | |
吲哚美辛/水 | 5 | 空气 | 0.6 | 0.6 | [ |
0.6 | [ |
表2 影响最终产品粒径的参数
Table 2 Parameters affecting particle size of the final product
溶质/溶剂 | 进料速率/( | 干燥气 | 干燥气速/(m3/h) | 产品粒径/μm | 文献 |
---|---|---|---|---|---|
[ | |||||
黑索今/丙酮 | 空气 | — | 0.4~0.6 | [ | |
[ | |||||
奥克托今/丙酮 | 10 | 35 | 1 | [ | |
吲哚美辛/水 | 5 | 空气 | 0.6 | 0.6 | [ |
0.6 | [ |
溶质(溶剂) | 超临界 流体 | 制备 方法 | 颗粒尺寸/μm | 文献 |
---|---|---|---|---|
利多卡因 | CO2 | RESS | 0.1 | [ |
胰岛素(甲醇) | CO2 | GAS | 0.2~0.7 | [ |
胰岛素(乙酸乙酯) | CO2 | GAS | 0.3~0.7 | [ |
胰岛素(乙醇) | CO2 | GAS | 0.05~0.3 | [ |
胰岛素(水) | NH3 | GAS | 0.2~0.3 | [ |
白蛋白(水) | CO2+乙醇 | SEDS | 0.05~0.5 | [ |
胰岛素(水) | CO2+乙醇 | SEDS | 0.05~0.5 | [ |
阿莫西林(N-甲基吡咯烷酮) | CO2 | ASES | 0.2~0.8 | [ |
氯苯扎利二钠(水) | CO2+乙醇 | ASES | 0.2~0.6 | [ |
硫酸沙丁胺醇 | CO2 | PGSS | 0.69 | [ |
丙氨酸 | CO2 | PGSS | 0.3~0.5 | [ |
表3 超临界流体技术制备超细晶体
Table 3 Ultrafine crystals prepared by supercritical fluid technology
溶质(溶剂) | 超临界 流体 | 制备 方法 | 颗粒尺寸/μm | 文献 |
---|---|---|---|---|
利多卡因 | CO2 | RESS | 0.1 | [ |
胰岛素(甲醇) | CO2 | GAS | 0.2~0.7 | [ |
胰岛素(乙酸乙酯) | CO2 | GAS | 0.3~0.7 | [ |
胰岛素(乙醇) | CO2 | GAS | 0.05~0.3 | [ |
胰岛素(水) | NH3 | GAS | 0.2~0.3 | [ |
白蛋白(水) | CO2+乙醇 | SEDS | 0.05~0.5 | [ |
胰岛素(水) | CO2+乙醇 | SEDS | 0.05~0.5 | [ |
阿莫西林(N-甲基吡咯烷酮) | CO2 | ASES | 0.2~0.8 | [ |
氯苯扎利二钠(水) | CO2+乙醇 | ASES | 0.2~0.6 | [ |
硫酸沙丁胺醇 | CO2 | PGSS | 0.69 | [ |
丙氨酸 | CO2 | PGSS | 0.3~0.5 | [ |
制备方法 | 优点 | 缺点 | |
---|---|---|---|
自下而上法 | 溶析结晶 | 操作流程简单,设备简易,颗粒粒度分布窄,生产费用低, 易于产业放大 | 粒度分布调控复杂,影响产品质量因素较多, 颗粒易聚结 |
喷雾干燥结晶 | 产品质量均一,过程连续可控同,适应性强 | 产品易聚结,不适用于一些热分解温度低的物质 | |
超临界流体技术 | 操作灵活,无溶剂残留 | 涉及高压设备,物质利用度低,工业放大困难 | |
自上而下法 | 介质研磨法 | 适用性强,操作简单,易于工业放大 | 引入杂质,耗时,颗粒粒度分布宽 |
高压均质化技术 | 易于产业放大,可以实现每小时几百升到几千升的产量 | 引入高压设备,耗时耗能,产品性质易发生改变,粒度分布宽 |
表4 超细晶体制备方法优缺点汇总
Table 4 Summary of advantages and disadvantages of ultrafine crystal preparation methods
制备方法 | 优点 | 缺点 | |
---|---|---|---|
自下而上法 | 溶析结晶 | 操作流程简单,设备简易,颗粒粒度分布窄,生产费用低, 易于产业放大 | 粒度分布调控复杂,影响产品质量因素较多, 颗粒易聚结 |
喷雾干燥结晶 | 产品质量均一,过程连续可控同,适应性强 | 产品易聚结,不适用于一些热分解温度低的物质 | |
超临界流体技术 | 操作灵活,无溶剂残留 | 涉及高压设备,物质利用度低,工业放大困难 | |
自上而下法 | 介质研磨法 | 适用性强,操作简单,易于工业放大 | 引入杂质,耗时,颗粒粒度分布宽 |
高压均质化技术 | 易于产业放大,可以实现每小时几百升到几千升的产量 | 引入高压设备,耗时耗能,产品性质易发生改变,粒度分布宽 |
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