Insight into the conformational polymorph transformation of a block-buster multiple sclerosis drug fingolimod hydrochloride (FTY 720).
Single-crystal structures of fingolimod hydrochloride (FTY 720), a block-buster multiple sclerosis drug, were revealed for the first time in this study. Three different conformational polymorphs (designated as forms I-III) were characterized using a variety of analytical techniques, including single-crystal XRD, VT-PXRD, DSC, HSM, and VT-confocal Raman spectroscopy. A temperature-dependent solid-solid transformation between different conformational polymorphs was observed to be reversible, and the transition process was studied using both VT-PXRD and VT-Raman techniques. Structural analysis revealed that the FTY 720 molecules adopt distinctive conformations in different polymorphs. Single-crystal to single-crystal transformation from form I to II was observed and was closely monitored by X-ray diffraction.
Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Jian-Rong
JR
Wang
Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Sha
S
Li
Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Bingqing
B
Zhu
Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: xuefengmei@simm.ac.cn.
Xuefeng
X
Mei
D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D000068876:Fingolimod Hydrochloride / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009103:Multiple Sclerosis; D013059:Spectrum Analysis, Raman; D014961:X-Ray Diffraction
D000068876:Fingolimod Hydrochloride
Conformational polymorphism; Fingolimod hydrochloride; Polymorph transformation; Single-crystal to single-crystal; Thermal analysis