Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives
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Passive gastrointestinal absorption and membrane retention of twelve esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP), as well as of these two non-esterified acids were estimated using PAMPA test. Artificial PAMPA membrane used in this study for the simulation of gastrointestinal barrier was solution of egg lecithin in dodecane (1 % w/v). All tested compounds belong to class III (high membrane retention and low permeation), whereas EDCP, dipentyl ester of PDCP (DPE-PDCP) and diisopentyl ester of PDCP (DIPE-PDCP) belong to class I (negligible membrane retention and low permeation). Finally, quantitative structure – permeability and structure – retention relationships models were created in order to find quantitative relationships between physico-chemical properties of tested compounds and PAMPA membrane permeability/membrane retention parameters. Statistically the most reliable models... were analysed and used for the design of new compounds for which favourable membrane permeability and retention can be expected.
Keywords:(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives / Membrane permeability / Membrane retention / PAMPA
Source:Journal of Pharmaceutical and Biomedical Analysis, 2020, 184
- Elsevier B.V.
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- This is the peer-reviewed version of the following article: Tubić, B.; Dobričić, V.; Poljarević, J.; Savić, A.; Sabo, T.; Marković, B. Estimation of Passive Gastrointestinal Absorption and Membrane Retention Using PAMPA Test, Quantitative Structure-Permeability and Quantitative Structure-Retention Relationship Analyses of Ethylenediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid and 1,3-Propanediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid Derivatives. Journal of Pharmaceutical and Biomedical Analysis 2020, 184. https://doi.org/10.1016/j.jpba.2020.113213