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

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Jelena Savić, Vladimir Dobričić, Katarina Nikolic, Sote Vladimirov, Sanda Dilber, Jasmina Brborić
Prediction of gastrointestinal absorption of thirteen newly synthesized β-hydroxy-β-arylalkanoic acids (HAA) and ibuprofen was performed using PAMPA test. The highest values of PAMPA parameters (%T and Papp) 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 %T and −logPapp 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 %T and −logPapp were predicted by use of selected QSPR models. Designed derivatives should have better gastrointestinal absorption than HAA tested in this study.

Graphical abstract

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