In vitro prediction of gastrointestinal absorption of novel beta-hydroxy-beta-arylalkanoic acids using PAMPA technique

Abstract

Prediction of gastrointestinal absorption of thirteen newly synthesized beta-hydroxy-beta-arylalkanoic acids (HAA) and ibuprofen was performed using PAMPA test The highest values of PAMPA parameters (%Tand P-app) were calculated for 1C, 1B and 2C and these parameters were significantly lower in comparison to ibuprofen. QSPR analysis was performed in order to identify molecular descriptors with the highest influence on %Tand-logP(app) and to create models which could be used for the design of novel HAA with improved gastrointestinal absorption. Obtained results indicate that introduction of branched side chain, as well as introduction of substituents on one phenyl ring (which disturb symmetry of the molecule) could have positive impact on gastrointestinal absorption. On the basis of these results, six novel HAA were designed and PAMPA parameters %Tand-logP(app) were predicted by use of selected QSPR models. Designed derivatives should have better gastrointestinal absorption than HAA tested in this study.