Polyethylene glycol derivatization of the non-active ion in active pharmaceutical ingredient ionic liquids enhances transdermal delivery. (19th January 2017)

• Record Type: Journal Article
• Authors: Zavgorodnya, Oleksandra; Shamshina, Julia L.; Mittenthal, Max; McCrary, Parker D.; Rachiero, Giovanni P.; Titi, Hatem M.; Rogers, Robin D.
• Is Part Of: New journal of chemistry. Volume 41:Number 4(2017)
• Page Start: 1499
• Page End: 1508
• Publication Date: 2017-01-19
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c6nj03709g
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : Introducing PEGylated moieties into the counterion structure of API–ILs can significantly enhance the transport through a membrane without a solvent. Abstract : We report the synthesis of four salts composed of the salicylate anion ([Sal] − ) paired with tributylammonium ([HN444 ] + ), choline ([Cho] + ), 1-methylpyrrolidinium ([HMPyrr] + ), and triethylene glycol monomethyl ether tributylammonium ([mPEG3 N444 ] + ) cations. Three of the synthesized salts (room temperature liquids [mPEG3 N444 ][Sal] and [Cho][Sal], and a supercooled liquid [HN444 ][Sal]) belong to the category of ionic liquids (ILs), and one salt (solid [HMPyrr][Sal]) was a crystalline solid. ILs in their neat form were studied for membrane transport through a silicon membrane, and exhibited higher transport compared to a control experiment with sodium salicylate dissolved in mPEG3 OH as solvent, but lower membrane transport compared to salicylic acid dissolved in mPEG3 OH. The 'PEGylated' IL, [mPEG3 N444 ][Sal], crossed the membrane with an ca. ∼2.5-fold faster rate than that of any of the non-PEGylated ILs. This work demonstrates not only that API–ILs can eliminate the use of a solvent vehicle during application and notably transport through a membrane as opposed to a higher melting crystalline salt, but also that the membrane transport can be further enhanced by PEGylation of the counter ions.