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Identification of phase boundaries in anhydrate/hydrate systems
Joseph F Krzyzaniak1, Glenn R Williams, Nina Ni
1Pfizer Global Research and Development, Pfizer Inc., 558 Eastern Point Road, Groton, Connecticut 06340, USA.
Journal of Pharmaceutical Sciences
|April 25, 2007
Summary
Near-infrared spectroscopy revealed caffeine
Area of Science:
- Solid-state chemistry
- Physical chemistry
Background:
- Caffeine exists as multiple solvatomorphs, including anhydrous and hydrated forms.
- Understanding the phase behavior and interconversion kinetics of these forms is crucial for pharmaceutical development.
Purpose of the Study:
- To monitor the phase conversion between anhydrous and hydrated caffeine solvatomorphs.
- To determine the kinetics and phase boundary of caffeine solvatomorph interconversion under varying conditions.
- To establish a method for rapidly assessing solvatomorph stability and interconversion rates.
Main Methods:
- Near-infrared (NIR) spectroscopy was employed to track phase transformations.
- Kinetic data were collected as a function of time, temperature, and relative humidity (RH).
- Phase boundary data were fitted using a second-order polynomial.
Main Results:
- Transformation kinetics increased with temperature.
- Conversion rates were dependent on the difference between ambient RH and the system's equilibrium water activity.
- Phase boundaries were determined: ~67% RH at 10°C, 74.5% RH at 25°C, and 86% RH at 40°C.
- Anhydrous caffeine is stable below the phase boundary, while the hydrate is stable above.
Conclusions:
- The study provides a method to rapidly determine solvatomorph stability relationships and interconversion kinetics.
- This approach is critical for selecting optimal drug forms, designing stability studies, and developing robust manufacturing processes for Active Pharmaceutical Ingredients (APIs).
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