Conformational polymorphs of isotretinoin and their impact on physicochemical and biological properties

doi:10.1016/j.ijpharm.2021.121222

	Conformational polymorphs of isotretinoin and their impact on physicochemical and biological properties
	Cheng, Yinxiang 1,2; Rong, Xiaoyi 1; Xia, Mengyuan 1,2; Zhang, Zaiyong 1; Wang, Jian-Rong 1; Mei, Xuefeng 1,2
刊名	INTERNATIONAL JOURNAL OF PHARMACEUTICS
	2021-12-15
卷号	610 页码:10
关键词	Polymorph Isotretinoin Stability Solubility Bioavailability
ISSN号	0378-5173
DOI	10.1016/j.ijpharm.2021.121222
通讯作者	Wang, Jian-Rong(jrwang@simm.ac.cn) ; Mei, Xuefeng(xuefengmei@simm.ac.cn)
英文摘要	Isotretinoin is the first-line drug for treatment of severe acne. Only one polymorph was reported even though it has been launched for nearly 40 years, and its clinic application was however limited by its stability and solubility challenges. In our study, two new polymorphs of isotretinoin were discovered and fully characterized. The transformation relationships between these solid forms were fully discussed, and a visible color change during single-crystal-to-single-crystal phase transition with the conformational change was investigated. Form II is determined to be thermodynamic stable form at room temperature, but metastable form at body temperature. The results show that form II is an ideal solid state possessing both superior thermal stability (60celcius, open air) and higher absorption once delivered into body. The thermal stability can be associated with the crystal structure such as torsion angle. The relative bioavailability of form II is higher than form I as expected, and the bioavailability of form II formulation is about 2 times as that of the marketed form I capsule. Therefore, form II formulation could provide an alternative for better performing isotretinoin.
资助项目	Shanghai Science and Technology Innovation Action Plan[20142201800]
WOS关键词	RETINOIC ACID ; CRYSTAL-STRUCTURE ; CIS-STILBENE ; PHOTOISOMERIZATION ; ISOMERIZATION ; CHEMISTRY ; TRETINOIN ; ACNE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000718950500008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/299030]
专题	中国科学院上海药物研究所
通讯作者	Wang, Jian-Rong; Mei, Xuefeng
作者单位	1.Chinese Acad Sci, Pharmaceut Analyt & Solid State Chem Res Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Cheng, Yinxiang,Rong, Xiaoyi,Xia, Mengyuan,et al. Conformational polymorphs of isotretinoin and their impact on physicochemical and biological properties[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2021,610:10.
APA	Cheng, Yinxiang,Rong, Xiaoyi,Xia, Mengyuan,Zhang, Zaiyong,Wang, Jian-Rong,&Mei, Xuefeng.(2021).Conformational polymorphs of isotretinoin and their impact on physicochemical and biological properties.INTERNATIONAL JOURNAL OF PHARMACEUTICS,610,10.
MLA	Cheng, Yinxiang,et al."Conformational polymorphs of isotretinoin and their impact on physicochemical and biological properties".INTERNATIONAL JOURNAL OF PHARMACEUTICS 610(2021):10.