Characterization of amorphous API:Polymer mixtures using X-ray powder diffraction.
Ann Newman1, David Engers, Simon Bates
1SSCI, An Aptuit Company, West Lafayette, Indiana, USA. ann.newman@aptuit.com
Journal of Pharmaceutical Sciences
|March 21, 2008
Summary
A new X-ray powder diffraction (XRPD) method using pair distribution functions (PDF) offers a more accurate assessment of amorphous API-polymer miscibility than traditional differential scanning calorimetry (DSC). This advanced technique reveals phase separation in systems where DSC may fail, providing crucial insights into material stability.
Area of Science:
- Materials Science
- Pharmaceutical Science
- Physical Chemistry
Background:
- Determining amorphous API-polymer miscibility traditionally relies on differential scanning calorimetry (DSC) to identify glass transition temperatures (Tg).
- Limitations exist with DSC, particularly for systems with nanoscale phase separation, potentially leading to misinterpretations of miscibility.
- Accurate miscibility assessment is critical for predicting physical stability and performance of amorphous solid dispersions.
Purpose of the Study:
- To develop and validate a novel X-ray powder diffraction (XRPD) method, coupled with pair distribution function (PDF) analysis, for assessing amorphous API-polymer miscibility.
- To compare the efficacy of the XRPD-PDF method against traditional DSC measurements.
- To investigate the miscibility and phase behavior of specific API-polymer systems.
Main Methods:
- Utilized X-ray powder diffraction (XRPD) to analyze amorphous mixtures of dextran-poly(vinylpyrrolidone) (PVP), trehalose-dextran, and indomethacin-PVP.
- Computed pair distribution functions (PDF) from XRPD data to characterize the local atomic arrangements.
- Correlated PDF profiles with differential scanning calorimetry (DSC) measurements of glass transition temperatures (Tg).
Main Results:
- The XRPD-PDF method successfully identified phase-separated systems, such as dextran-PVP and trehalose-dextran, by matching component PDFs to the mixture PDF.
- Indomethacin-PVP was confirmed as miscible, showing a unique PDF profile distinct from its components, aligning with DSC results.
- The XRPD-PDF method revealed phase separation in trehalose-dextran, a system where DSC indicated miscibility due to nanoscale domains (<30 nm).
Conclusions:
- The XRPD-PDF method provides a more comprehensive assessment of amorphous API-polymer miscibility than DSC, especially for systems with nanoscale phase separation.
- Trehalose-dextran forms a phase-separated solid nanosuspension, not a true miscible system, highlighting the limitations of DSC for such materials.
- Understanding nanoscale phase separation is crucial for predicting the physical stability and crystallization tendency of amorphous solid dispersions.
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