Polymorphism of Triamcinolone Acetonide Acetate and Its Implication for the Morphology Stability of the Finished Drug Product

doi:10.1021/acs.cgd.7b00453

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	Polymorphism of Triamcinolone Acetonide Acetate and Its Implication for the Morphology Stability of the Finished Drug Product
	Wang, Jian-Rong; Zhu, Bingqing; Zhang, Zaiyong; Bao, Junjie; Deng, Gaojin; Ding, Qiaoce; Mei, Xuefeng
刊名	CRYSTAL GROWTH & DESIGN
	2017-06
卷号	17 期号:6 页码:3482-3490
ISSN号	1528-7483
DOI	10.1021/acs.cgd.7b00453
文献子类	Article
英文摘要	Triamcinolone acetonide acetate,(TAA) is a widely applied drug for rheumatoid arthritis and for the treatment of chronic inflammatory diseases. The drug was marketed as an injectable suspension with very low aqueous solubility. It was found that significant changes in crystal form, particle size, and morphology were observed during the shelf life period, which resulted in product lot failure and recall. TAA was thus an interesting subject for polymorphism screening and led to the discovery of multiple solid modifications, including three polymorphs (A, B, and C) and a monohydrate. These forms were fully characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy, dynamic vapor sorption, and zeta potential. Single-crystal structures of four different forms and the transformation pathways among different modifications were discussed in detail. Single-crystal-to-single-crystal transformation behaviors were also analyzed and monitored by variable temperature-powder X-ray diffraction and hot stage microscopy. Morphological stability, form change, and particle size in suspension were also closely monitored, and the data were compared with the marketed product. It was found that crystal form selection plays a critical role in the stability of the injectable suspension products. The results indicate that form B has better physical stability in 0.5% NaCMC aqueous suspension compared to that of the currently marketed form.
资助项目	National Natural Science Foundation of China[81402898] ; Youth Innovation Promotion Association CAS[2016257] ; CAS Key Technology Talent Program[00000000] ; SANOFI-SIBS Scholarship[00000000]
WOS关键词	CRYSTAL-STRUCTURES ; KINETIC ASPECTS ; PSEUDOPOLYMORPHISM ; FORMS ; TRANSFORMATION ; NANOPARTICLES ; TRIMORPHISM ; INSIGHT
WOS研究方向	Chemistry ; Crystallography ; Materials Science
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000403136200066
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272641]
专题	药物质量控制与固体化学研究中心
通讯作者	Mei, Xuefeng
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Pharmaceut Analyt & Solid State Chem Res Ctr, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Jian-Rong,Zhu, Bingqing,Zhang, Zaiyong,et al. Polymorphism of Triamcinolone Acetonide Acetate and Its Implication for the Morphology Stability of the Finished Drug Product[J]. CRYSTAL GROWTH & DESIGN,2017,17(6):3482-3490.
APA	Wang, Jian-Rong.,Zhu, Bingqing.,Zhang, Zaiyong.,Bao, Junjie.,Deng, Gaojin.,...&Mei, Xuefeng.(2017).Polymorphism of Triamcinolone Acetonide Acetate and Its Implication for the Morphology Stability of the Finished Drug Product.CRYSTAL GROWTH & DESIGN,17(6),3482-3490.
MLA	Wang, Jian-Rong,et al."Polymorphism of Triamcinolone Acetonide Acetate and Its Implication for the Morphology Stability of the Finished Drug Product".CRYSTAL GROWTH & DESIGN 17.6(2017):3482-3490.