PAMPA
The Parallel Artificial Membrane Permeability Assay (PAMPA) assay is used as an in vitro model of passive, transcellular permeability. An artificial membrane immobilized on a filter is placed between a donor and acceptor compartment. At the start of the test, a drug with a UV chromophore is introduced in the donor compartment. Following the permeation period, the concentration of drug in the donor and acceptor compartments is measured using UV spectroscopy.
Pion has published 23 articles on PAMPA in peer-reviewed journals in collaboration with academics and pharmaceutical scientists from the industry including Dr. Manfred Kansy (Hoffman-La Roche, CH), founder of the PAMPA method.
Aqueous Double-Sink™ PAMPA The large majority of all compounds, even with low aqueous solubility, are amendable to this approach. Incubation times are selected to obtain the most reliable permeability measurements.
Cosolvent Double-Sink™ PAMPA For samples with ultralow solubility that fails the aqueous method, cosolvents are used to extend the range of the PAMPA technique. It is very common to find that compounds with low solubility often have exceedingly high permeability.
Resources: The information is accessible by creating an account. After you log in (located at top of page next to search), the linked pdf files that can be viewed and downloaded.
Pion's Approach
Gastrointestinal Permeability The gastrointestinal tract (GIT) has a pH range from pH 1 – 8. Since the pH of the blood is pH 7.4; there exists a pH gradient between the GIT and the plasma that can affect the transport of ionizable molecules. In an effort to simulate this pH gradient, we have chosen pH 7.4 for the acceptor compartment, and a pH range of 5.0, 6.2, and 7.4 in the donor compartment. To model transport conditions in the blood, the acceptor contains a scavenger binding molecule. Pion’s GIT-0 phospholipid is used for the assay.
Blood-Brain Barrier Permeability CNS Screening of candidate drug molecules is done using a PAMPA assay to model blood-brain barrier (BBB) permeability. Rodent in vivo and in situ studies of the kinetics of drug uptake across the BBB are valuable tools for assessing factors important to steady-state brain penetration. These are relatively expensive and time consuming assays to do, and are done only sparingly. Animal studies can be augmented by PAMPA, which for BBB uses a mixture of phospholipids infused into lipophilic microfilters, with net negative lipid charge, a system mimicking many of the properties of brain lipid membranes. The data is used to predict brain uptake kinetics, as indicated by PS values determined by in situ perfusion methods.
Skin Penetration Researchers and product developers can now measure drug permeability with a proprietary test system that is highly predictive of the human skin barrier. Unlike conventional skin test methods, Pion’s high throughput method is faster, less expensive and may be conducted manually or on robotic platforms.
The Skin PAMPA Test System excels as a complimentary screen prior to Franz Cell testing due to the lower cost, enhanced usability, higher throughput and reduced sample requirements. Pre-coated with a proprietary formulation, the 96 well plates are disposable, which completely eliminates cross contamination and the additional time and labor required for washing glass cells. Permeability measurements with the artificial skin-mimetic membrane exhibit a high correlation as tested against human skin in Franz cells.
To submit your compounds for GIT, BBB or Skin PAMPA:
- Fill out a sample submission form for each compound. Include a submission form with the samples shipped to Pion
