Absorption properties of non-steroidal anti-inflammatory drugs and their amino acid derivatives

Abstract

The principal objectives of this work were: i) to examine the absorption properties of ibuprofen in a range of different buffer solutions; ii) to study the absorption properties and mechanisms of ibuprofen, ketoprofen and naproxen; and iii) to determine the effect that coupling the ibuprofen molecule to a range of simple amino acids has on its absorption properties and gastrointestinal irritation. Preliminary studies involved the examination of eight different buffers that had been previously used in absorption/perfusion studies as reported in the literature. The solubility of ibuprofen acid in each system varied six-fold over the range of buffers and was related to the buffer pH. Ibuprofen formed poorly soluble salts with calcium ions in Krebs' buffer and became solubilised in fed state simulated intestinal fluid (FeSSIF). Buffer capacity varied significantly over the eight systems. Buffer composition was found to significantly affect the absorption properties of ibuprofen. This appeared to be primarily due to differences in net water flux/solvent drag across the intestinal mucosa as a consequence of different buffer osmolarities.