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Solid-state behavior of cromolyn sodium hydrates
L R Chen1, V G Young, D Lechuga-Ballesteros
1Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Journal of Pharmaceutical Sciences
|November 17, 1999
Summary
Cromolyn sodium (CS) exhibits variable solid-state behavior due to continuous water sorption, leading to a flexible crystal structure rather than distinct stoichiometric hydrates. This understanding is crucial for drug formulation and processing.
Area of Science:
- Pharmaceutical Sciences
- Solid-State Chemistry
- Crystallography
Background:
- Cromolyn sodium (CS) is an antiasthmatic and antiallergenic drug with incompletely understood solid-state properties.
- CS forms nonstoichiometric hydrates, exhibiting continuous water sorption/desorption with hysteresis, leading to physical variability that complicates formulation.
- Existing data on CS hydrates are controversial, partly due to variable powder X-ray diffraction (PXRD) patterns indicating structural instability.
Purpose of the Study:
- To elucidate the unusual water uptake of CS by examining its molecular and crystal structures.
- To correlate CS crystal structure with PXRD patterns using Rietveld analysis.
- To determine if CS exists as different stoichiometric hydrates or exhibits a variable crystal structure.
Main Methods:
- Crystal structure determination of CS at 295 K and 173 K with varying water stoichiometry.
- Rietveld analysis of PXRD patterns from CS powder equilibrated at different relative humidities.
- Preparation and characterization of recently described solid forms of CS.
Main Results:
- The crystal structure of CS with 6.44 water molecules per CS molecule was solved at 295 K and 173 K, revealing similar packing but different lattice parameters compared to previous reports.
- A flexible 2-hydroxy-propane chain in CS appears to accommodate variable water amounts; disorder in sodium ion coordination and water positions contributes to nonstoichiometry.
- Rietveld analysis quantitatively explained PXRD peak shifts by changes in unit cell parameters, supporting a variable crystal structure.
- New solid forms of CS were identified as the original crystalline form contaminated with the M mesophase.
Conclusions:
- CS possesses a variable crystal structure accommodating nonstoichiometric amounts of water, rather than existing as distinct stoichiometric hydrates.
- The flexibility of the CS molecule and disorder in sodium ion coordination sites facilitate continuous water sorption.
- Understanding CS's variable solid-state behavior is essential for optimizing its pharmaceutical formulation and processing.