Drug Permeability Profiling Using the Novel Permeapad® 96-Well Plate
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Here, first experiences with a prototype tool for high throughput (passive) permeability profiling, a 96-well plate comprising the Permeapad® membrane, are reported. The permeabilities of a set of drugs were determined and compared to published measures of oral absorption, such as human fraction absorbed (F a ) and in vitro permeability values obtained using other tools.
Methods
The tool consists of a 96-well bottom and screen plate with the artificial, phospholipid-based barrier (Permeapad®) mounted between the plates' lower and upper compartments. The permeability of 14 model compounds including high- and low-absorption drugs, cationic, anionic, zwitterionic and neutral molecules, was determined by quantifying the compounds' transport over time, deriving the steady-state flux from the linear part of the cumulative curves and calculating the apparent permeability (P app ). The membrane structure was investigated in a high-resolution digital light microscope.
Results
The Permeapad® 96-well plate was found suited to distinguish high and low absorption drugs and yielded a hyperbolic correlation to F a . The P app values obtained were congruent with those determined with in-house prepared Permeapad® in the Franz cell set-up. Furthermore, good to excellent correlations were seen with Caco-2 permeability (R 2 = 0.70) and PAMPA permeability (R 2 = 0.89). Microscopic investigation of the Permeapad® barrier revealed the formation of phospholipid vesicles and myelin figures in aqueous environment.
- Source: Jacobsen, A.-C., Nielsen, S., Brandl, M., & Bauer-Brandl, A. (2020). Drug permeability profiling using the novel Permeapad® 96-well plate. Pharmaceutical Research, 37 , Article 93. available at: https://doi.org/10.1007/s11095-020-02787-3