Molecular Mobility In Pharmaceutical Glasses: Implications On Physical Stability
2016-05
Loading...
View/Download File
Persistent link to this item
Statistics
View StatisticsJournal Title
Journal ISSN
Volume Title
Title
Molecular Mobility In Pharmaceutical Glasses: Implications On Physical Stability
Authors
Published Date
2016-05
Publisher
Type
Thesis or Dissertation
Abstract
Amorphous pharmaceuticals have gained widespread importance due to their advantageous increase in solubility and dissolution rate. However, a major challenge with this approach is the high risk of physicochemical instability in comparison to its crystalline counterparts. The goal of my research was to investigate the correlations between molecular mobility and physical stability in model amorphous systems (both drug substance and solid dispersions), specifically in the glassy state. This will potentially enable development of effective strategies to stabilize amorphous pharmaceuticals. Use of time-temperature, time-aging and time-concentration superposition principle enabled comprehensive characterization of structural relaxation behavior in the glassy state. This was followed by the investigation of correlation between crystallization behavior and different mobility modes in glassy celecoxib and indomethacin. Structural relaxation time correlated well with characteristic crystallization time in the supercooled state. On the other hand, a stronger correlation was observed between the Johari-Goldstein relaxation time and physical instability in the glassy state but not with structural relaxation time. Effect of polymer additive and polymer concentration on the structural relaxation behavior in nifedipine dispersions was investigated. We found that stronger drug-polymer interactions enhanced physical stability by reducing the molecular mobility. With an increase in polymer concentration, the relaxation times were longer indicating a decrease in molecular mobility. The effect of sorbed water on molecular mobility and physical stability in a model amorphous drug and dispersion was also evaluated. Sorbed water, in a concentration dependent manner, increased mobility and accelerated crystallization - attributable to the plasticization effect of water. The extent of coupling between molecular mobility and crystallization time (defined as time for 2.5% crystallization) was found to be unaffected in the range of water content studied ( < 2% w/w). Based on this finding, we have proposed the use of “water sorption” as an accelerated stability approach to predict crystallization in slow crystallizing systems.
Keywords
Description
University of Minnesota Ph.D. dissertation. May 2016. Major: Pharmaceutics. Advisor: Raj Suryanarayanan. 1 computer file (PDF); xii, 177 pages.
Related to
Replaces
License
Collections
Series/Report Number
Funding information
Isbn identifier
Doi identifier
Previously Published Citation
Suggested citation
Mehta, Mehak. (2016). Molecular Mobility In Pharmaceutical Glasses: Implications On Physical Stability. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/199039.
Content distributed via the University Digital Conservancy may be subject to additional license and use restrictions applied by the depositor. By using these files, users agree to the Terms of Use. Materials in the UDC may contain content that is disturbing and/or harmful. For more information, please see our statement on harmful content in digital repositories.