Sulfasalazine in ionic liquid form with improved solubility and exposure

Autor:	Julia L. Shamshina, Bei-Ching Chuang, Jing-Tao Wu, Gabriela Gurau, Emily Guan, S. Hailu, Robert J. Griffin, Mohammad Shadid, Robin D. Rogers, Syed A. A. Rizvi, Swapan Chowdhury
Rok vydání:	2015
Předmět:	Pharmacology Chromatography Chemistry medicine.medical_treatment Organic Chemistry Pharmaceutical Science Absorption (skin) Biochemistry Excretion chemistry.chemical_compound Sulfasalazine In vivo Drug Discovery medicine Molecular Medicine Solubility Saline medicine.drug ADME Choline chloride
Zdroj:	MedChemComm. 6:1837-1841
ISSN:	2040-2511 2040-2503
DOI:	10.1039/c5md00290g
Popis:	The absorption, distribution, metabolism, and excretion (ADME) properties of a cholinium ionic liquid (IL) salt of the poorly soluble drug sulfasalazine were evaluated in both in vitro and in vivo models. The IL exhibited about a 4000-fold improvement in saline solubility over the neutral drug and the improved solubility was translated to corresponding improvement in exposure where dose linear exposure after intravenous I.V. administration was demonstrated. Upon administration to rats, a sulfasalazine:choline chloride (1:1) physical mixture and the IL had equivalent I.V. exposures at a low solution dose of 0.5 mg kg−1. However, the superior solubility of the IL enabled administration of much higher I.V. doses (6, 12, and 24 mg kg−1, dissolved directly in saline), which resulted in a dose proportional increase in exposure.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::011eb21d9aa9856567429c7ba9174c75 https://doi.org/10.1039/c5md00290g Zobrazit plný text záznamu