Are you frustrated by the lack of precise passive permeability data for BCS prediction?
Are you unable to measure which excipients best improve dermal absorption?
Are you challenged by the lack of tools to test topical formulations before ex vivo/in vitro human skin studies?
Pion PAMPA technology is a high throughput method for measuring passive trans-membrane permeability and flux. Various membranes are available to mimic the gastro-intestinal conditions, the blood-brain or human skin barrier. The passive permeability of API’s as well as the absorption potential provided by simple or complex formulations can be evaluated using the robust models and protocols. If you need to measure passive permeability of compounds using only small quantities, our system provides the answer. If simple solvent/excipient effect on flux needs to be studied or complex formulations needs to be evaluated and compared, our comparative flux assay on the PAMPA platform will provide robust and reliable answers.
- Permeability classification of APIs
- Pre-formulation excipient screening
- Formulation screening
Gastrointestinal Permeability for BCS (Biopharmaceutical Classification System)
To properly predict the absorption potential of newly discovered active pharmaceutical ingredients (API’s), assay parameters should simulate the in vivo conditions. 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 that helps to keep the free concentration of the API close to zero. Additionally, Pion’s GIT-0 phospholipid is used for the assay that mimics the composition of brush border membranes to get high quality predictions.
Blood-Brain Barrier Permeability for CNS classification
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 Permeability for dermal/transdermal penetration potential
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. Skin PAMPA is pre-coated with a proprietary formulation that has been proven to be predictive for human skin penetration in multiple studies published in peer-reviewed journals. Being developed on the same platform, the skin PAMPA model is easy to adopt by laboratories running other PAMPA models, while new installations also easily accomplished.
Preformulation Excipient Screening
A comparative flux assay for smart excipient selection enhancing GI absorption
Generally, formulation strategies incorporating solubilizing excipients are explored in early drug development. However, the effect of excipients on GIT permeability is not usually taken into account. In the case of sparingly soluble, but otherwise promising molecules, early excipient screening is beneficial in prioritizing and even minimizing the number of animal tests required. We have developed a cost-effective protocol on our double-sink PAMPA platform to study the effect of excipients on the solubility and permeability of APIs. The data generated may be used in the early assessment of excipient influenced and pH-dependent GIT absorption.
A comparative flux assay to select excipients for dermal/transdermal formulations
Transdermal drug delivery has become one of the most popular alternative drug administration routes, with numerous benefits recognized over the past few decades. The main barrier and regulator of transport through the skin is the stratum corneum (SC), the outermost layer of the epidermis. An estimation of skin penetration of compounds designed for dermal usage or transdermal delivery is needed in the early stages of development, when the in vitro or in vivo human skin studies are not feasible to use. The skin PAMPA protocol has been modified to fill this gap and to provide valuable predictions of the complex effects of excipients and solvents on solubility and permeability.
||Q48 Human skin
||42.63 ± 9.15
||51.34 ± 5.08
||39.59 ± 8.35
||66.13 ± 7.25
||34.96 ± 8.33
||43.97 ± 4.68
||30.17 ± 9.08
||41.31 ± 5.74
||20.96 ± 4.33
||35.55 ± 3.05
||14.79 ± 5.70
||27.19 ± 1.55
||11.45 ± 2.50
||23.15 ± 0.71
Comparing the performance of topical and transdermal formulations
Testing of formulations requires a different approach compared to the standard PAMPA application, as the aim of these studies is to investigate the performance of formulations, not just the pure API. The modification affects the applied dose, the method of application and the calculated parameters. The skin PAMPA setup has been modified to make it suitable for topical formulation testing. Formulations may be tested in their native form and can be evaluated based on the permeated amount. The below study compares data from 3 formulations measured on human skin in vitro and skin PAMPA: