In situ 3D topographic and shape analysis by synchrotron radiation X-ray microtomography for crystal form identification in polymorphic mixtures.
Polymorphism denotes the existence of more than one crystal structure of a substance, and great practical and theoretical interest for the chemical and pharmaceutical industries. In many cases, it is challenging to produce a pure crystal form and establish a sensitive detection method for the identification of crystal form in a mixture of polymorphs. In this study, an accurate and sensitive method based on synchrotron radiation X-ray computed microtomography (SR-μCT) was devised to identify the polymorphs of clopidogrel bisulphate (CLP). After 3D reconstruction, crystal particles were extracted and dozens of structural parameters were calculated. Whilst, the particle shapes of the two crystal forms were all irregular, the surface of CLP II was found to be rougher than CLP I. In order to classify the crystal form based on the quantitative morphological property of particles, Volume Bias Percentage based on Surface Smoothing (VBP) was defined and a new method based on VBP was successfully developed, with a total matching rate of 99.91% for 4544 particles and a lowest detectable limit of 1%. More important for the mixtures in solid pharmaceutical formulations, the interference of excipients can be avoided, a feature cannot achieved by other available analytical methods.
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.|Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
Xian-Zhen
XZ
Yin
Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201204, China.
Ti-Qiao
TQ
Xiao
School of Chemistry, University of Hyderabad, Hyderabad 500046, India.
Ashwini
A
Nangia
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
Shuo
S
Yang
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
Xiao-Long
XL
Lu
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
Hai-Yan
HY
Li
Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
Qun
Q
Shao
Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201204, China.
You
Y
He
Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
Peter
P
York
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
Ji-Wen
JW
Zhang