Effective gelation of water by an amphiphilic drug.
We report the formation of aqueous gels at low concentrations (less than 1 wt%) of an amphiphilic drug, a derivative of a chromane-2-carboxylic acid, at pH values 6.2-6.4. Formation of gels in the vicinity of the apparent pK(a) of the drug suggests that on the molecular level, the gels are composed of the aggregates of the ionized and protonated forms of the drug, which are stabilized by hydrogen bonding and hydrophobic interactions. In contrast, its identical analog, which differs by one methylene group, did not form gels or viscous solutions. We believe that additional steric hindrance, brought by the presence of the bulkier ethyl group (as compared to methyl group), prevents efficient interaction between the carboxylic acid groups thus hindering the gelation process.
Peresypkin
Andrey V
AV
Merck & Co Inc, Pharmaceutical R&D, PO Box 2000, Rahway, New Jersey 07065, USA. andrey_peresypkin@merck.com
Ellison
Martha E
ME
Panmai
Sunny
S
Cheng
Yu
Y
D002839:Chromans / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005782:Gels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D012996:Solutions; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*