Amorphous solid dispersions (ASDs) can potentially increase the apparent solubility and thereby the oral bioavailability of poorly soluble compounds. However, their physical instability, i.e., potential to crystallize, is a major concern. Our objective was to explore methods for rapid assessment of the physical stability of ASDs. Ketoconazole ASDs were prepared with each of the three polymers, poly(acrylic acid) (PAA), poly(2-hydroxyethyl methacrylate) (PHEMA), and polyvinylpyrrolidone (PVP). The physical stability of these ASDs was evaluated after exposure to 90% RH (25 °C) in an automated water sorption analyzer. The onset time for ketoconazole crystallization, induced by water sorption, was rank ordered as PAA > PHEMA > PVP. Additionally, the ability of the polymers to inhibit crystallization on contact with aqueous medium was studied by powder X-ray diffractometry using synchrotron radiation. In this case, the rank ordering was PAA ∼ PHEMA > PVP. To check the validity of our approach, the long-term stability of ketoconazole in ASDs was evaluated in the glassy state, both at 25 and at 40 °C, and was rank ordered as PAA > PHEMA > PVP. Crystallization, accelerated by water vapor sorption, can serve as an effective preliminary screening tool to rapidly evaluate and rank order the physical stability of ASDs.
|Original language||English (US)|
|Number of pages||8|
|Journal||Crystal Growth and Design|
|State||Published - May 3 2017|
Bibliographical noteFunding Information:
The project was partially funded by the William and Mildred Peters endowment fund and the Centre for Pharmaceutical Processing and Research. Parts of thiswork were carried out in the Characterization Facility, University of Minnesota, a member of the NSF-funded Materials Research Facilities Network This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. We thank Dr. Gregory Halder and Dr. Wenqian Xu at Argonne National Laboratory for their help during the synchrotron data collection.
© 2017 American Chemical Society.