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Slow dissolution behaviour of amorphous capecitabine.
Jelte Meulenaar1, Jos H Beijnen, Jan H M Schellens
1Department of Pharmacy & Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands. Jelte.Meulenaar@slz.nl
International Journal of Pharmaceutics
|December 11, 2012
Summary
Amorphous capecitabine dissolves slower than crystalline forms due to gelling in water. This unique property, linked to its low glass transition temperature, enables stable sustained-release drug formulations with reduced excipient needs.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
Background:
- Amorphous capecitabine typically exhibits faster dissolution than crystalline forms.
- Understanding amorphous solid-state properties is crucial for drug formulation.
Purpose of the Study:
- To investigate the anomalous dissolution behavior of amorphous capecitabine.
- To explore the potential of amorphous capecitabine in sustained-release formulations.
Main Methods:
- Dissolution testing of amorphous and crystalline capecitabine.
- Infrared (IR) spectroscopy and Differential Scanning Calorimetry (DSC) analysis.
- Evaluation of amorphous capecitabine stability in aqueous environments.
Main Results:
- Amorphous capecitabine demonstrated significantly slower dissolution compared to its crystalline form.
- A "gelling" phenomenon was observed, where amorphous capecitabine forms a stable gel upon contact with water, entrapping the drug.
- The gelled state was stable and did not recrystallize, even with increased water or temperature, attributed to a low glass transition temperature (Tg 19°C).
Conclusions:
- The anomalous dissolution of amorphous capecitabine is due to a water-induced gelling effect.
- This stable gelling property offers a novel approach for developing sustained-release formulations.
- Reduced excipient requirements make this approach clinically feasible for high-dosed drugs like capecitabine.
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