Dexamethasone Ibuprofen Prodrug Synthesis and Preliminary Kinetic Study

Abstract

The synthesis of prodrug dexamethasone conjugated with ibuprofen through a spacer arm amino acid. The potential new prodrug will decrease the gastrointestinal side effects and may change the site of absorption. The synthesis of N-[2-(4-isobutyl-phenyl) propionyl]-glycine (compound 2), which was linked to the Dexamethasone to obtain the final conjugated prodrug (N-[2-(4-isobutyl phenyl) propionyl]-glycine,21-ester with (9-fluoro-11β,17,21 trihydroxy-16α-methyl-pregna-1,4-diene-3,20-dione) (compound 4), detected through UV, IR, and CHN elemental microanalysis. Column chromatography was used for the purification and isolation of compound 4 using gradient elution technique. The kinetic study showed the release of Dexamethasone in different buffers after 10-20 hours using in vitro dissolution. Kinetic study of the synthesized prodrug using High-Pressure Liquid Chromatography (HPLC), Dexamethasone and compound 4 were prepared in different dilutions ranging from 10-70 µg mL-1 in order to determine their specificity, linearity, precision and accuracy.