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Characterization of Solid-State Drug Polymorphs and Real-Time Evaluation of Crystallization Process Consistency by Near-Infrared Spectroscopy
Qi, Shu-Ye1,2; Tian, Ye1; Zou, Wen-Bo1; Hu, Chang-Qin1
2018-10-22
Source PublicationFRONTIERS IN CHEMISTRY
ISSN2296-2646
Volume6Pages:7
Abstract

Herein, we aimed to develop a strategy for evaluating the consistency of pharmaceutically important crystallization processes in real time, focusing on two typical cases of polymorphism. Theoretical analysis using a combination of C-13 solid-state nuclear magnetic resonance spectroscopy with other polymorphism analysis techniques identified a number of marker signals, the changes of which revealed the presence of two or more structural orientations (lattices and/or molecular conformations) in both cefazolin sodium pentahydrate (alpha-CEZ-Na) and cephathiamidine (CETD). The proportions of these forms were shown to be batch-dependent and were defined as critical quality attributes (CQAs) to evaluate process consistency. Subsequently, real-time analysis by chemometrics-assisted near-infrared spectroscopy (NIR) was used to obtain useful information corresponding to CQAs. The pretreated spectra of representative samples were transformed by first derivative and vector normalization methods and used to calculate standard deviations at each wavelength and thus detect significant differences. As a result, vibrational responses of H2O, CH3, and CH2 moieties (at 5,280, 4,431, and 4,339 cm(-1), respectively) were shown to be sensitive to the CQAs of alpha-CEZ-Na, which allowed us to establish a highly accurate discrimination model. Moreover, signals of H2O, CONH, and COOH moieties (at 5,211, 5,284, and 5,369 cm(-1), respectively) played the same role in the case of CETD, as confirmed by theoretical results. Thus, we established a technique for the rapid evaluation of crystallization process consistency and deepened our understanding of crystallization behavior by using NIR in combination with polymorphism analysis techniques.

KeywordProcess Consistency Drug Polymorph Solid-state Nuclear Magnetic Resonance Spectroscopy Near-infrared Spectroscopy Raman Microscopy
DOI10.3389/fchem.2018.00506
Language英语
WOS KeywordCefazolin Sodium Pentahydrate ; Pharmaceutical Quality ; Nmr ; Form ; Design
Funding ProjectNational Major Scientific and Technological Special Project for Significant New Drugs Development[2017ZX09101001-007]
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
Funding OrganizationNational Major Scientific and Technological Special Project for Significant New Drugs Development
WOS IDWOS:000447826900001
PublisherFRONTIERS MEDIA SA
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/26224
Collection中国科学院过程工程研究所
Corresponding AuthorHu, Chang-Qin
Affiliation1.Natl Inst Food & Drug Control, Beijing, Peoples R China
2.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Qi, Shu-Ye,Tian, Ye,Zou, Wen-Bo,et al. Characterization of Solid-State Drug Polymorphs and Real-Time Evaluation of Crystallization Process Consistency by Near-Infrared Spectroscopy[J]. FRONTIERS IN CHEMISTRY,2018,6:7.
APA Qi, Shu-Ye,Tian, Ye,Zou, Wen-Bo,&Hu, Chang-Qin.(2018).Characterization of Solid-State Drug Polymorphs and Real-Time Evaluation of Crystallization Process Consistency by Near-Infrared Spectroscopy.FRONTIERS IN CHEMISTRY,6,7.
MLA Qi, Shu-Ye,et al."Characterization of Solid-State Drug Polymorphs and Real-Time Evaluation of Crystallization Process Consistency by Near-Infrared Spectroscopy".FRONTIERS IN CHEMISTRY 6(2018):7.
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