Journal
CRYSTAL GROWTH & DESIGN
Volume 16, Issue 12, Pages 7286-7300Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.cgd.6b01470
Keywords
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Funding
- Merck Co., Inc.
- National Science Foundation [DMR-1309218]
- NSF [CHE-1465154]
- American Association of Pharmaceutical Scientists
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1465154] Funding Source: National Science Foundation
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Bile salts are natural surfactants present in the human gastrointestinal tract. Therefore, it is essential to consider their effect on the dissolution and crystallization tendency of oral drug formulations. Although a recent study showed that sodium taurocholate delayed nucleation for 11 structurally diverse compounds, there is limited information about the crystallization inhibition properties of other bile salts and whether they are interchangeable in this context. In this study, we evaluated the ability of 13 bile salts to maintain supersaturated aqueous solutions of three compounds: celecoxib, nevirapine, and fibanserin. Most bile salts extended nucleation induction times. However, their inhibitory effects varied depending on the structure and concentration of the bile salt and the drug. The R5 group and hydrophobicity of the bile salt appeared to be essential. Molecular dynamics simulations indicated that van der Waals and hydrogen bonding interactions occurred between nevirapine and bile salts, with variations in different systems. These results are important to better understand the crystallization tendency of orally delivered poorly water-soluble compounds in vivo.
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