Multicomponent System of NPS-1034, an Orally Administered Lung Cancer Drug Candidate, with Sulfonic Acids and Solid State Characterization
- Authors
- Lee, Jangmi; Park, Suzie; Yoon, Seon-Joo; Jung, Yong Woo; Byun, Youngjoo; Yuk, Soon Hong; Jeon, Min Keyong; Kang, Sung Kwon; Lee, Eun Hee
- Issue Date
- 9월-2013
- Publisher
- AMER CHEMICAL SOC
- Keywords
- multicomponent system; drug candidate; sulfonic acid; salt; solid state characterization
- Citation
- CRYSTAL GROWTH & DESIGN, v.13, no.9, pp.3958 - 3968
- Indexed
- SCIE
SCOPUS
- Journal Title
- CRYSTAL GROWTH & DESIGN
- Volume
- 13
- Number
- 9
- Start Page
- 3958
- End Page
- 3968
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/102336
- DOI
- 10.1021/cg400651f
- ISSN
- 1528-7483
- Abstract
- NPS-1034 is a drug candidate targeted for the regulation of c-MET/AXL receptor tyrosin kinase activity. NPS-1034 was developed to improve efficacy and reduce toxicity by targeting c-MET/AXL related signaling pathways. However, NPS-1034 is practically insoluble in almost all organic solvents as well as aqueous media (pH 1, 4.5, and 7.5). We attempted to improve the physicochemical properties of NPS-1034 by forming multicomponent systems with a wide variety of sulfonic acids including methanesulfonic acid, 1,2-ethanedisulfonic acid, p-toluenesulfonic acid, and camphorsulfonic acid. Solid state characterization of NPS-1034 salts and amorphous with sulfonic acids was conducted, and the crystal structures of four salts and NPS-1034 were compared and investigated. Sulfonic acid salts of NPS-1034 decreased the melting point of NPS-1034 as much as -155.43 degrees C. Solubilities of NPS-1034 and salts of NPS-1034 were measured to develop lipid-based formulation for the GLP toxicity study. Solvents studied include oleic acid, poly(ethylene glycol) 400, and ethanol. Solubility of amorphous of NPS-1034 with camphorsulfonic acid showed a significant increase in all three solvents. This work will give some insight into how various types of sulfonic acids interact with pharmaceutically important compounds containing the pyrrolepyridine moiety.
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Collections - College of Pharmacy > Department of Pharmaceutical Science > 1. Journal Articles
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