Membrane, artificial permeability

When screening for absorption by passive membrane permeability, artificial membranes have the advantage of offering a highly reproducible and high-throughput system. Artificial membranes have been compared to Caco-2 cells and for passive... 

Fujikawa M, Ano R, Nakao K, Shimizu R and Akamatsu M. Relationships between structure and high-throughput screening permeability of diverse drugs with artificial membranes application to prediction of Caco-2 cell permeability. Bioorg Med Chem 2005 13 4721-32. 

Wohnsland, F., Faller, B. High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes. J. Med. 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

Kansy, M., Senner, F., Gubemator, K. Physicochemical high throughput screening parallel artificial membrane permeability assay in the description of passive absorption processes. J. Med. Chem. 1998, 41, 1007-1010. 

Typical early in vitro permeability assessments measure the rate of flux of a compound from one side of a barrier to another [54, 55]. The barrier has historically been derived from a cell line, most commonly Caco-2 or Madin-Darby canine kidney (MDCK) cells. In the last several years, there has been substantial work and significant progress in the development of parallel artificial membrane permeability... 

BBB PAMPA Blood brain barrier parallel artificial membrane permeability assay... 

HISTORICAL DEVELOPMENTS IN ARTIFICIAL-MEMBRANE PERMEABILITY MEASUREMENT... 

PARALLEL ARTIFICIAL-MEMBRANE PERMEABILITY ASSAY (PAMPA)... 

THE CASE FOR THE IDEAL IN VITRO ARTIFICIAL MEMBRANE PERMEABILITY MODEL... 

Figure 7.15 Kinetics of transport across a filter-immobilized artificial membrane (a) desipramine and (b) dihydromethysticin concentrations in acceptor well. [Reprinted from Avdeef, A., in van de Waterbeemd, H. Lennemas, H. Artursson, R (Eds.). Drug Bioavailability. Estimation of Solubility, Permeability, Absorption and Bioavailability. Wiley-VCH Weinheim, 2003 (in press), with permission from Wiley-VCH Verlag GmbH.]...

The lengthy permeability chapter (Chapter 7) recounts the study of many different artificial membrane formulations, comparing transport results of each to human jejunal permeabilities. A very promising in vitro screening system was described the double-sink sum-Pe PAMPA GIT model. It is most applicable to molecules that are classified as soluble in the BCS scheme. 

Ong, S. Liu, H. Pidgeon, C., Immobilized-artificial-membrane chromatography Measurements of membrane partition coefficient and predicting drug membrane permeability, J. Chromatogr. A 728, 113-128 (1996). 

Zhu, C. Chen, T.-M. Hwang, K., A comparative study of parallel artificial membrane permeability assay for passive absorption screening, in CPS A2000 The Symposium on Chemical and Pharmaceutical Structure Analysis. Milestone Development Services. Princeton, NJ, Sept. 26-28, 2000. 

Avdeef, A. Strafford, M. Block, E. Balogh, M. P. 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. 14, 271-280 (2001). 

Sugano, K. Hamada, H. Machida, M. Ushio, H., High throughput prediction of oral absorption Improvement of the composition of the lipid solution used in parallel artificial membrane permeability assay, J. Biomolec. Screen. 6, 189-196 (2001). 

This book is written for the practicing pharmaceutical scientist involved in absorption-distribution-metabolism-excretion (ADME) measurements who needs to communicate with medicinal chemists persuasively, so that newly synthesized molecules will be more drug-like. ADME is all about a day in the life of a drug molecule (absorption, distribution, metabolism, and excretion). Specifically, this book attempts to describe the state of the art in measurement of ionization constants (p Ka), oil-water partition coefficients (log PI log D), solubility, and permeability (artificial phospholipid membrane barriers). Permeability is covered in considerable detail, based on a newly developed methodology known as parallel artificial membrane permeability assay (PAMPA). 

The transport of both solute and solvent can be described by an alternative approach that is based on the laws of irreversible thermodynamics. The fundamental concepts and equations for biological systems were described by Kedem and Katchalsky [6] and those for artificial membranes by Ginsburg and Katchal-sky [7], In this approach the transport process is defined in terms of three phenomenological coefficients, namely, the filtration coefficient LP, the reflection coefficient o, and the solute permeability coefficient to. 

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