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Published on: July 4, 2014
Precipitation from amorphous solid dispersions in biorelevant dissolution testing: The polymorphism of regorafenib
Martin Müller1, Florian Platten2, Martin Dulle3
1Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Düsseldorf, Germany, Universitätsstraße 1, 40225 Düsseldorf, Germany; INVITE GmbH, Formulation Technology, Chempark, Building W 32, 51368 Leverkusen, Germany.
Amorphous solid dispersions (ASDs) improve drug absorption. This study reveals that Regorafenib precipitates in various forms, including amorphous structures, influencing drug bioavailability and formulation strategies.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Drug Delivery
Background:
- Amorphous solid dispersions (ASDs) enhance bioavailability of poorly water-soluble drugs.
- Precipitate state (amorphous vs. crystalline) is crucial but less understood.
- Regorafenib monohydrate (RGF MH), a BCS class II drug, was formulated as an ASD.
Purpose of the Study:
- Investigate the precipitation process of RGF in ASDs.
- Characterize the physicochemical properties of RGF precipitates.
- Understand the impact of excipients (povidone K25, HPMCAS) on precipitation.
Main Methods:
- Biorelevant dissolution studies.
- Offline analysis: SEM, DSC, CRM, XRPD, SAXS.
- In-situ analysis: WAXS, ITC for precipitation tracking.
Main Results:
- RGF precipitates formed with varying drug content.
- Identified crystalline RGF and amorphous RGF-HPMCAS co-precipitates.
- PVP suppressed amorphous co-precipitate formation.
- RGF precipitates in multiple polymorphic states based on conditions.
Conclusions:
- RGF precipitation is complex, influenced by dissolution media and excipients.
- Engineered amorphous structures in vivo may offer a novel formulation approach.
- Understanding precipitate behavior is key for optimizing ASDs.
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