H. Bundgaard, N. M. Nielsen
Apr 1, 1988
Citations
2
Influential Citations
47
Citations
Quality indicators
Journal
International Journal of Pharmaceutics
Abstract
Abstract Various glycolamide esters of 13 acidic non-steroidal anti-inflammatory drugs were prepared with the aim of obtaining enzymatically labile ester prodrugs. The glycolamide esters were in general found to be hydrolyzed very rapidly in human plasma solutions, the half-lives of hydrolysis being seconds or a few minutes in 80% plasma for some N , N -disubstituted glycolamide esters. In contrast, simple methyl or ethyl esters of the carboxylic acid agents were found to be hydrolyzed only very slowly in plasma solutions and thus unsuitable as prodrug forms. Since the esters of N , N -disubstituted glycolamides combine a high susceptibility to undergo enzymatic hydrolysis in plasma with a high stability in aqueous solution, they are suggested to be a useful prodrug type for several non-steroidal anti-inflammatory acids with the aim of e.g. depressing their gastrotoxicity and improving their delivery characteristics. With respect to the latter aspect it was shown that it is possible to design glycolamide ester derivatives with widely varying water solubilities and lipophilicities and still maintain a high lability of the esters to enzymatic hydrolysis.