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A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
Solid-state characterization of an NR2B selective N-methyl d-aspartate (NMDA) antagonist polymorphs
Takashi Kojima1, Morimichi Sato, Atsushi Omura
1Pfizer Global Research and Development, Nagoya Laboratories, Pfizer Japan Inc., 5-2 Taketoyo, Aichi 470-2393, Japan. tak_kojimajpn@yahoo.co.jp
International Journal of Pharmaceutics
|February 5, 2008
Summary
This study characterizes three polymorphic forms of compound A, an NR2B selective N-methyl D-aspartate (NMDA) antagonist. Forms II and III exhibit an enantiotropic relationship, with distinct crystal structures compared to form I.
Area of Science:
- Pharmaceutical Chemistry
- Solid-State Chemistry
- Crystallography
Background:
- Compound A, a selective NR2B antagonist for N-methyl D-aspartate (NMDA) receptors, exists in multiple crystalline forms.
- Polymorphism significantly impacts drug properties, including solubility, stability, and bioavailability.
Purpose of the Study:
- To prepare and characterize the known polymorphic forms (I and II) of compound A.
- To identify and investigate potential new polymorphic forms and their relationships.
- To elucidate the crystallographic differences between the identified forms.
Main Methods:
- Single crystal X-ray diffractometry for structural determination.
- Differential scanning calorimetry (DSC) for thermal analysis.
- Variable temperature powder X-ray diffractometry (VT-PXRD) for phase transitions and temperature-dependent behavior.
Main Results:
- Two polymorphs (forms I and II) were successfully prepared and characterized.
- DSC and VT-PXRD indicated the existence of at least three polymorphic forms (I, II, and a new form III).
- Forms II and III demonstrated an enantiotropic relationship, with distinct crystallographic parameters and molecular arrangements compared to form I.
Conclusions:
- Compound A exhibits complex polymorphism with at least three distinct crystalline forms.
- The enantiotropic relationship between forms II and III provides crucial insights into solid-state behavior.
- Understanding these polymorphic forms is essential for optimizing the development and formulation of compound A.
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