Use of a Plasticizer for Physical Stability Prediction of Amorphous Solid Dispersions

Fung, Michelle H.; Suryanarayanan, Raj

doi:10.1021/acs.cgd.7b00625

Use of a Plasticizer for Physical Stability Prediction of Amorphous Solid Dispersions

Journal Article · Fri Jun 23 00:00:00 EDT 2017 · Crystal Growth and Design

DOI:https://doi.org/10.1021/acs.cgd.7b00625· OSTI ID:1406627

Fung, Michelle H. ^[1]; ^[1]

Univ. of Minnesota, Minneapolis, MN (United States)

Utilizing glycerol as a plasticizer, an accelerated physical stability testing method of amorphous solid dispersions (ASDs) was developed. The influence of glycerol concentration on the glass transition temperature and α-relaxation time (a measure of molecular mobility) of amorphous ketoconazole, celecoxib, and the solid dispersions of each prepared with polyvinylpyrrolidone was investigated. By temperature scaling (T_g/T), the effects of glycerol concentration and temperature on the relaxation time were simultaneously evaluated. Glycerol, in a concentration dependent manner, accelerated crystallization in all of the systems without affecting the fragility. In celecoxib-PVP ASDs, the drug crystallization was well coupled to molecular mobility and was essentially unaltered at glycerol concentrations up to 2% w/w. The acceleration in crystallization brought about by glycerol expedited the determination of the coupling between molecular mobility and crystallization. As a result, we were able to predict the physical stability of the unplasticized ASD. Lastly, this approach is especially useful for ASDs with high polymer content where drug crystallization is extremely slow at the relevant storage temperature.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1406627

Journal Information:: Crystal Growth and Design, Journal Name: Crystal Growth and Design Journal Issue: 8 Vol. 17; ISSN 1528-7483

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
alcohols
amorphous solid dispersions
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crystallization
dielectric spectroscopy
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polymers
stability

Use of a Plasticizer for Physical Stability Prediction of Amorphous Solid Dispersions

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