Journal
CRYSTAL GROWTH & DESIGN
Volume 15, Issue 6, Pages 2593-2597Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.cgd.5b00392
Keywords
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Funding
- Merck
- National Science Foundation [DMR 1309218]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1309218] Funding Source: National Science Foundation
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Poor aqueous solubility Of new therapeutic agents is one of the most pressing current challenges in drug delivery. Supersaturated solutions, generated in vivo either by virtue of the-intrinsic compound properties (i.e., Ionization behavior) or by dissolution of formulations containing a high energy form of the drug, are considered one of the most promising approaches to improve drug absorption, when it is limited by solubility. The,Challenge is to maintain supersaturation, typically achieved by adding polymeric crystallization inhibitors, for biologically relevant time periods. In this study, we present exciting preliminary observations about the,potential role of bile salts as crystallization inhibitors. Focusing on sodium taurocholate, an endogenous bile salt also widely used in simulated intestinal media, extended experimental nucleation induction times were observed in the presence of the surfactant for a,group of 11 diverse compounds, relative to induction times in buffer. Limited studies with two additional bile salts suggested,other members of the le salt family may also have crystallization inhibition properties. Given the endogenous nature of bile salts, as well as their use in simulated intestinal media, these observations are clearly Of potential importance when assessing the supersaturation behavior of poorly water-soluble compounds.
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