Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 104, Issue 6, Pages 1981-1992Publisher
WILEY-BLACKWELL
DOI: 10.1002/jps.24423
Keywords
amorphous; crystallization; polymers; solid dispersion; supersaturation
Funding
- US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
Ask authors/readers for more resources
Amorphous materials are high-energy solids that can potentially enhance the bioavailability of poorly soluble compounds. A major impediment to their widespread use as a formulation platform is the tendency of amorphous materials to crystallize. The aim of this study was to evaluate the relative crystallization tendency of six structural analogues belonging to the dihydropyridine class, in an aqueous environment in the absence and presence of polymers, using wide-angle X-ray scattering synchrotron radiation and polarized light microscopy. The crystallization behavior of precipitates generated from supersaturated solutions of the active pharmaceutical ingredients was found to be highly variable ranging from immediate to several hours in the absence of polymers. Polymers with intermediate hydrophilicity/hydrophobicity were found to substantially delay crystallization, whereas strongly hydrophilic or hydrophobic polymers were largely ineffective. Nuclear magnetic resonance spectroscopy experiments supported the supposition that polymers need to have affinity for both the drug-rich precipitate and the aqueous phase in order to be effective crystallization inhibitors. This study highlights the variability in the crystallization tendency of different compounds and provides insight into the mechanism of inhibition by polymeric additives. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1981-1992, 2015
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available