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Crystallization and transitions of sulfamerazine polymorphs
Geoff G Z Zhang1, Chonghui Gu, Mark T Zell
1Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, Minnesota 55455-0343, USA.
Journal of Pharmaceutical Sciences
|April 12, 2002
Summary
Sulfamerazine polymorph II, crucial for drug formulation, was successfully prepared. This study details its properties and transition kinetics, revealing it as the stable form at lower temperatures.
Area of Science:
- Pharmaceutical Sciences
- Solid-State Chemistry
Background:
- Sulfamerazine exists in two known polymorphic forms, I and II.
- Understanding polymorph behavior is critical for drug efficacy and stability.
Purpose of the Study:
- To prepare bulk sulfamerazine polymorph II with controlled particle size.
- To characterize both sulfamerazine polymorphs (I and II).
- To investigate the thermodynamics and kinetics of polymorph transitions.
Main Methods:
- Optical microscopy
- Powder X-ray diffractometry (PXRD)
- Differential scanning calorimetry (DSC)
- Carbon-13 solid-state nuclear magnetic resonance (13C ssNMR)
- Aqueous solubility and density measurements
Main Results:
- Sulfamerazine polymorphs I and II are enantiotropes.
- The thermodynamic transition temperature is between 51-54°C, with polymorph II being the stable form below this temperature.
- Interconversion between polymorphs exhibits slow kinetics under various conditions (heating, cooling, milling, compaction, solvent contact).
- Ostwald's Rule of Stages explains crystallization and the delayed discovery of polymorph II.
Conclusions:
- First-time preparation of bulk sulfamerazine polymorph II with narrow particle size distribution.
- Established the enantiotropic relationship and transition kinetics between sulfamerazine polymorphs.
- Polymorph II is the thermodynamically stable form at typical storage temperatures, impacting formulation strategies.