title: Visualization and quantification of deformation behavior of clopidogrel bisulfate polymorphs during tableting.
abstract: The deformation behavior of particles under pressure dominates the mechanical properties of solid dosage forms. In this study, the in situ 3D deformation of two polymorphs (I and II) of clopidogrel bisulfate (CLP) was determined to illustrate pressure distribution profiles within the tablet by the deformation of the crystalline particles for the first time. Synchrotron radiation X-ray computed microtomography (SR-μCT) was utilized to visualize and quantify the morphology of thousands crystalline particles of CLP I and CLP II before and after compression. As a result, the deformation was examined across scale dimensions from microns to the size of the final dosage form. Three dimensional parameters such as volume, sphericity, oblate and prolate of individual particle and distributions were computed and analyzed for quantitative comparison to CLP I and CLP II. The different degrees of deformation under the same compression conditions of CLP I and CLP II were observed and characterized quantitatively. The map of deformation degrees within the tablet illustrated the heterogeneous pressure distribution in various regions of the compacted tablet. In conclusion, the polymorph deformation behaviors demonstrated by SR-μCT quantitative structure analysis deepen understanding of tableting across dimensions from microns to millimeters for the macrostrcuture of tablet.
authors.affiliation: 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.
authors.forename: Xian-Zhen
authors.initials: XZ
authors.lastname: Yin
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.|School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.|Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Li
authors.affiliation: Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201204, China.
authors.forename: Ti-Qiao
authors.initials: TQ
authors.lastname: Xiao
authors.affiliation: Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: York
authors.affiliation: School of Chemistry, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Nangia
authors.affiliation: Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Shuang-Ying
authors.initials: SY
authors.lastname: Gui
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.|School of Life Sciences, Jilin University, Changchun 130012, China.|Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Ji-Wen
authors.initials: JW
authors.lastname: Zhang
mesh_terms: D000077144:Clopidogrel; D019245:Compressive Strength; D003460:Crystallization; D004339:Drug Compounding; D008855:Microscopy, Electron, Scanning; D011312:Pressure; D013607:Tablets / Q000737:chemistry*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000737:chemistry; D014961:X-Ray Diffraction; D055114:X-Ray Microtomography
chemical_list: D013607:Tablets; D000077144:Clopidogrel; D013988:Ticlopidine