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A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
A practical method to predict physical stability of amorphous solid dispersions.
Stéphanie Greco1, Jean-René Authelin, Caroline Leveder
1Sanofi, Vitry-sur-Seine, France. Stephanie.greco@sanofi-aventis.com
Pharmaceutical Research
|March 17, 2012
Summary
This study developed a method to predict amorphous solid dispersion crystallization time using temperature and moisture. The findings enable prediction of long-term stability and optimized storage conditions.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
Background:
- Amorphous solid dispersions (ASDs) are crucial for drug delivery, but their physical stability, particularly crystallization, is a major concern.
- Controlling crystallization kinetics is essential for ensuring the long-term efficacy and shelf-life of pharmaceutical formulations.
Purpose of the Study:
- To establish a predictive model for the crystallization time of amorphous solid dispersions.
- To investigate the combined influence of temperature and moisture content on crystallization kinetics.
- To develop a stress testing program for predicting long-term stability.
Main Methods:
- Amorphous samples of spray-dried API and Hydroxypropylmethylcellulose Phtalate were subjected to various temperature and humidity conditions.
- Crystallization onset was monitored using X-ray powder diffraction (XRPD).
- Glass transition temperature (Tg) and water sorption were quantified using modulated Differential Scanning Calorimetry (mDSC) and water sorption analysis.
Main Results:
- A linear relationship was observed between the logarithm of crystallization onset time and the Tg/T ratio under conditions below Tg.
- Extrapolation of data from above Tg provided only a qualitative trend for conditions below Tg.
- Data from accelerated conditions (crystallization < 3 months) could be extrapolated to predict stability over 15 months.
Conclusions:
- The developed methodology serves as an effective stress program for predicting long-term stability of ASDs.
- This approach allows for the design of optimal temperature and humidity conditions for storage to prevent API crystallization.
- The findings contribute to ensuring the quality and shelf-life of amorphous solid dispersion formulations.
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