A Novel Design of Artificial Membrane for Improving the PAMPA Model

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2008 Jan 11

PMID 18185985

Citations 74

Authors

Xiaoxi Chen

Anthony Murawski

Karishma Patel

Charles L Crespi

Praveen V Balimane

Affiliations

Soon will be listed here.

Abstract

Purpose: Since the first demonstration of PAMPA, the artificial membrane has been traditionally prepared by impregnating a porous filter with a solution of lipid mixture. While the lipid solution-based method is simple and seems to provide good predictability for many compounds, it is challenged by several shortcomings including reproducibility, stability, mass retention and the incorrect prediction of a group of highly permeable compounds including caffeine and antipyrine. Here we present the validation of a novel artificial membrane formed by constructing a lipid/oil/lipid tri-layer in the porous filter.

Methods: Permeability values obtained from traditional and new artificial membrane were compared for their correlation with Caco-2 and human absorption values. Mass retention, stability and organic solvent compatibility of the new artificial membrane were studied.

Results: The new artificial membrane correctly predicts the permeability of the traditionally under-predicted compounds and improves the correlation with Caco-2 and human absorption values. Furthermore, the new artificial membrane reduces the mass retention of compounds that are highly retained by the traditional artificial membrane. The new artificial membrane is also found to be robust enough to sustain long term storage and has good compatibility with organic solvents.

Conclusions: The new artificial membrane provides an improved PAMPA model.

Citing Articles

Long-Chain Cyclic Arylguanidines as Multifunctional Serotonin Receptor Ligands with Antiproliferative Activity.

Zareba P, Drabczyk A, Wnorowski A, Maj M, Rurka P, Malarz K ACS Omega. 2025; 10(7):6446-6469.

PMID: 40028084 PMC: 11866022. DOI: 10.1021/acsomega.4c06456.

Norditerpene natural products from subterranean fungi with anti-parasitic activity.

Kolas A, Rusman Y, Maia A, Williams J, Fumuso F, Cotto-Rosario A bioRxiv. 2025; .

PMID: 39803491 PMC: 11722346. DOI: 10.1101/2025.01.02.631097.

New Conjugates of Vancomycin with Cell-Penetrating Peptides-Synthesis, Antimicrobial Activity, Cytotoxicity, and BBB Permeability Studies.

Ruczynski J, Prochera K, Kazmierczak N, Kosznik-Kwasnicka K, Piechowicz L, Mucha P Molecules. 2024; 29(23).

PMID: 39683678 PMC: 11643744. DOI: 10.3390/molecules29235519.

Novel Alkynylamide-Based Nonpeptidic Allosteric Inhibitors for SARS-CoV-2 3-Chymotrypsin-like Protease.

Xue J, Li H, Wang R, Wang M, Chen X, Deng Y ACS Pharmacol Transl Sci. 2024; 7(10):3170-3191.

PMID: 39421662 PMC: 11481521. DOI: 10.1021/acsptsci.4c00369.

Low-Basicity 5-HT Receptor Ligands from the Group of Cyclic Arylguanidine Derivatives and Their Antiproliferative Activity Evaluation.

Zareba P, Drabczyk A, Wnorowski A, Maj M, Malarz K, Rurka P Int J Mol Sci. 2024; 25(19).

PMID: 39408617 PMC: 11477289. DOI: 10.3390/ijms251910287.

References

Avdeef A, Artursson P, Neuhoff S, Lazorova L, Grasjo J, Tavelin S . Caco-2 permeability of weakly basic drugs predicted with the double-sink PAMPA pKa(flux) method. Eur J Pharm Sci. 2005; 24(4):333-49. DOI: 10.1016/j.ejps.2004.11.011. View

Balimane P, Han Y, Chong S . Current industrial practices of assessing permeability and P-glycoprotein interaction. AAPS J. 2006; 8(1):E1-13. PMC: 2751418. DOI: 10.1208/aapsj080101. View

Wohnsland F, Faller B . High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes. J Med Chem. 2001; 44(6):923-30. DOI: 10.1021/jm001020e. View

Balimane P, Chong S . Cell culture-based models for intestinal permeability: a critique. Drug Discov Today. 2005; 10(5):335-43. DOI: 10.1016/S1359-6446(04)03354-9. View

Liu H, Sabus C, Carter G, Du C, Avdeef A, Tischler M . In vitro permeability of poorly aqueous soluble compounds using different solubilizers in the PAMPA assay with liquid chromatography/mass spectrometry detection. Pharm Res. 2003; 20(11):1820-6. DOI: 10.1023/b:pham.0000003380.44755.5a. View

Artursson P, Borchardt R . Intestinal drug absorption and metabolism in cell cultures: Caco-2 and beyond. Pharm Res. 1998; 14(12):1655-8. DOI: 10.1023/a:1012155124489. View

Di L, Kerns E, Fan K, McConnell O, Carter G . High throughput artificial membrane permeability assay for blood-brain barrier. Eur J Med Chem. 2003; 38(3):223-32. DOI: 10.1016/s0223-5234(03)00012-6. View

Avdeef A, Strafford M, Block E, Balogh M, Chambliss W, Khan I . Drug absorption in vitro model: filter-immobilized artificial membranes. 2. Studies of the permeability properties of lactones in Piper methysticum Forst. Eur J Pharm Sci. 2001; 14(4):271-80. DOI: 10.1016/s0928-0987(01)00191-9. View

Alsenz J, Haenel E . Development of a 7-day, 96-well Caco-2 permeability assay with high-throughput direct UV compound analysis. Pharm Res. 2004; 20(12):1961-9. DOI: 10.1023/b:pham.0000008043.71001.43. View

10.

Balimane P, Pace E, Chong S, Zhu M, Jemal M, Van Pelt C . A novel high-throughput automated chip-based nanoelectrospray tandem mass spectrometric method for PAMPA sample analysis. J Pharm Biomed Anal. 2005; 39(1-2):8-16. DOI: 10.1016/j.jpba.2005.03.043. View

11.

Avdeef A, Bendels S, Di L, Faller B, Kansy M, Sugano K . PAMPA--critical factors for better predictions of absorption. J Pharm Sci. 2007; 96(11):2893-909. DOI: 10.1002/jps.21068. View

12.

Corti G, Maestrelli F, Cirri M, Zerrouk N, Mura P . Development and evaluation of an in vitro method for prediction of human drug absorption II. Demonstration of the method suitability. Eur J Pharm Sci. 2005; 27(4):354-62. DOI: 10.1016/j.ejps.2005.11.005. View

13.

Mueller P, RUDIN D, Tien H, WESCOTT W . Reconstitution of cell membrane structure in vitro and its transformation into an excitable system. Nature. 1962; 194:979-80. DOI: 10.1038/194979a0. View

14.

Avdeef A, Tsinman O . PAMPA--a drug absorption in vitro model 13. Chemical selectivity due to membrane hydrogen bonding: in combo comparisons of HDM-, DOPC-, and DS-PAMPA models. Eur J Pharm Sci. 2006; 28(1-2):43-50. DOI: 10.1016/j.ejps.2005.12.008. View

15.

Kansy M, Avdeef A, Fischer H . Advances in screening for membrane permeability: high-resolution PAMPA for medicinal chemists. Drug Discov Today Technol. 2014; 1(4):349-55. DOI: 10.1016/j.ddtec.2004.11.013. View

16.

Kansy M, Senner F, Gubernator K . Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes. J Med Chem. 1998; 41(7):1007-10. DOI: 10.1021/jm970530e. View

17.

Seo P, Teksin Z, Kao J, Polli J . Lipid composition effect on permeability across PAMPA. Eur J Pharm Sci. 2006; 29(3-4):259-68. DOI: 10.1016/j.ejps.2006.04.012. View

18.

Sugano K, Nabuchi Y, Machida M, Aso Y . Prediction of human intestinal permeability using artificial membrane permeability. Int J Pharm. 2003; 257(1-2):245-51. DOI: 10.1016/s0378-5173(03)00161-3. View

19.

Marino A, Yarde M, Patel H, Chong S, Balimane P . Validation of the 96 well Caco-2 cell culture model for high throughput permeability assessment of discovery compounds. Int J Pharm. 2005; 297(1-2):235-41. DOI: 10.1016/j.ijpharm.2005.03.008. View