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Dehydration, hydration behavior, and structural analysis of fenoprofen calcium
1Pharmaceutical Development Discovery and Analytical Sciences Departments, Glaxo Wellcome Inc., Five Moore Drive, Research Triangle Park, North Carolina 27709, USA.
Journal of Pharmaceutical Sciences
|July 18, 2001
Summary
Fenoprofen calcium dihydrate
Area of Science:
- Solid-state chemistry
- Pharmaceutical science
- Materials science
Background:
- Fenoprofen calcium (FC) is a nonsteroidal anti-inflammatory drug.
- Understanding the dehydration and rehydration behavior of FC dihydrate is crucial for its formulation and stability.
- Previous studies have not fully elucidated the structural and energetic aspects of FC dihydrate's phase transitions.
Purpose of the Study:
- To investigate the dehydration and rehydration mechanisms of fenoprofen calcium dihydrate.
- To determine the structural characteristics and water environments within the FC dihydrate crystal lattice.
- To correlate dehydration kinetics with the observed crystal structure.
Main Methods:
- Differential scanning calorimetry (DSC) for thermal analysis.
- Thermogravimetric analysis (TGA) to study dehydration kinetics.
- Powder X-ray diffractometry (PXRD) and single-crystal X-ray diffraction (XRD) for structural elucidation.
Main Results:
- The dehydration of FC dihydrate exhibits complex kinetics with two distinct activation energies (309 kJ/mol and 123 kJ/mol) attributed to different water molecule environments within the crystal structure.
- Single-crystal XRD revealed the coordination of calcium ions with fenoprofen anions and water molecules, detailing the crystal packing arrangement.
- Hot-stage PXRD indicated the formation of a partially crystalline monohydrate upon partial dehydration, with complete rehydration to the dihydrate occurring via a solution-mediated process.
Conclusions:
- The dehydration process of fenoprofen calcium dihydrate is strongly influenced by its crystal structure and the varying interactions of water molecules.
- The formation of a stable monohydrate intermediate and the solution-mediated rehydration pathway are key factors in the solid-state behavior of FC.
- These findings provide critical insights into the solid-state properties of fenoprofen calcium, essential for pharmaceutical development and manufacturing.