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Dynamic solid-state and tableting properties of four theophylline forms
E Suihko1, V P Lehto, J Ketolainen
1Department of Pharmaceutics, University of Kuopio, PO Box 1627, FIN-70211, Kuopio, Finland. eero.suihko@uku.fi
International Journal of Pharmaceutics
|April 9, 2001
Summary
Theophylline solid-state forms undergo transformations during storage, impacting their densification and compact properties. Water content significantly influences these changes, affecting drug formulation stability.
Area of Science:
- Pharmaceutical Sciences
- Solid-State Chemistry
- Materials Science
Background:
- Theophylline exists in various solid-state forms, including monohydrate (TMO), a mixture (TMIX), and anhydrous polymorphs I (TA-I) and II (TA-II).
- Understanding the relationships between these forms and their physical properties is crucial for pharmaceutical development.
Purpose of the Study:
- To investigate the solid-state transformations of theophylline forms.
- To evaluate the impact of these transformations on densification and compact properties.
- To determine the influence of water content on these behaviors.
Main Methods:
- Powder X-ray diffraction for solid-state identification.
- Compaction simulator for assessing deformation and preparing compacts.
- Porosity and tensile strength measurements after storage at controlled humidity.
Main Results:
- Theophylline anhydrous polymorph II (TA-II) is the stable form; TA-I, TMIX, and TMO transform to TA-II during storage.
- All forms primarily deform via plastic flow, with water content increasing viscoelasticity in TMIX and TMO.
- Densification and tensile strength of TMIX and TMO compacts change over time, approaching TA-II properties.
Conclusions:
- Dynamic solid-state transformations influence theophylline's densification and compact properties.
- Water content plays a critical role in the extent of these property changes.
- These findings are vital for predicting and controlling the stability of theophylline formulations.