Advances in crystallization of ultrafine crystals

doi:10.11949/0438-1157.20220468

Abstract

Abstract:

Ultrafine crystals are widely used in the medicine and chemical industry due to their smaller size and larger specific surface area. In this paper, the preparation methods of ultrafine crystals, principles and controlled parameters of particle size are reviewed in detail. The applications of ultrafine crystals in inhalation, energetic materials and poorly water insoluble drugs were summarized. Meanwhile, the stability of ultrafine crystals suspensions and particle aggregation were reviewed. Finally, we outlook the future development of ultrafine crystals.

Key words: crystallization, particle formation, stability, ultrafine crystal, agglomeration

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。

关键词: 结晶, 粒子形成, 稳定性, 超细晶体, 聚结

CLC Number:

TQ 026.5

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.

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.

Figures/Tables 11

References 76

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技术	溶质	溶剂/反溶剂	颗粒粒径/μm	文献
简单混合	安体舒通	丙酮/水	0.5	[39]
简单混合	非诺贝特	乙醇/水	约0.328	[40]
超声可控结晶	灰黄霉素	丙酮/水	1.04	[33]
超声可控结晶	布洛芬	丙酮/水	0.702	[41]
超声可控结晶	乙酰氯芬酸	乙醇/水	0.112	[42]
超重力溶析结晶	达那唑	乙醇/水	0.19	[36]

技术	溶质	溶剂/反溶剂	颗粒粒径/μm	文献
简单混合	安体舒通	丙酮/水	0.5	[39]
简单混合	非诺贝特	乙醇/水	约0.328	[40]
超声可控结晶	灰黄霉素	丙酮/水	1.04	[33]
超声可控结晶	布洛芬	丙酮/水	0.702	[41]
超声可控结晶	乙酰氯芬酸	乙醇/水	0.112	[42]
超重力溶析结晶	达那唑	乙醇/水	0.19	[36]

溶质/溶剂	进料速率/(ml/min)	干燥气	干燥气速/(m³/h)	产品粒径/μm	文献
戊四硝脂/丙酮	约10	N₂	1.30×10^-10	约0.49	[45]
黑索今/丙酮	约1	空气	—	0.4~0.6	[46]
镀铝硝铵/丙酮	10~15	空气	2.0~2.5	1	[47]
奥克托今/丙酮	10	N₂	35	1	[48]
吲哚美辛/水	5	空气	0.6	0.6	[49]
萘普生/水	5	空气	0.6	0.4	[49]

溶质/溶剂	进料速率/(ml/min)	干燥气	干燥气速/(m³/h)	产品粒径/μm	文献
戊四硝脂/丙酮	约10	N₂	1.30×10^-10	约0.49	[45]
黑索今/丙酮	约1	空气	—	0.4~0.6	[46]
镀铝硝铵/丙酮	10~15	空气	2.0~2.5	1	[47]
奥克托今/丙酮	10	N₂	35	1	[48]
吲哚美辛/水	5	空气	0.6	0.6	[49]
萘普生/水	5	空气	0.6	0.4	[49]

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	[53]
胰岛素（甲醇）	CO₂	GAS	0.2~0.7	[54]
胰岛素（乙酸乙酯）	CO₂	GAS	0.3~0.7	[55]
胰岛素（乙醇）	CO₂	GAS	0.05~0.3	[56]
胰岛素（水）	NH₃	GAS	0.2~0.3	[56]
白蛋白（水）	CO₂+乙醇	SEDS	0.05~0.5	[57]
胰岛素（水）	CO₂+乙醇	SEDS	0.05~0.5	[57]
阿莫西林（N-甲基吡咯烷酮）	CO₂	ASES	0.2~0.8	[58]
氯苯扎利二钠（水）	CO₂+乙醇	ASES	0.2~0.6	[59]
硫酸沙丁胺醇	CO₂	PGSS	0.69	[60]
丙氨酸	CO₂	PGSS	0.3~0.5	[61]