Developing alternative models for in vitro investigation of excipient influence on drug transport
Precious Akhuemokhan1, Magda Swedrowska1, Josie Williams1, Richard Harvey2, Ben Forbes1
1Institute of Pharmaceutical Science, School of Cancer and Pharmaceutical Sciences, King’s College London
2Institut für Pharmazie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.
This study explored the use of the Parallel Artificial Membrane Permeability Assay (PAMPA) to study the effect of excipients on the disposition of inhaled drugs. The main aim was to compare a PAMPA with the Calu-3 cell layer model by assessing the effect of glycerol on the permeability of radioactive small molecules utilised as probes for different routes of transport. The probes were a hydrophilic compound 14C-Mannitol for paracellular transport and the hydrophobic probes 3H-propranolol for transcellular transport. Results showed that the transport of both probes in the cell model was affected even at glycerol concentrations of 1% v/v and 2% v/v. Altered barrier permeability was evidenced by an increasing flux of mannitol due to disruption of tight junctions at these concentrations. In contrast, there was a reduction in propranolol permeability suggesting an effect of glycerol to reduce transcellular transport. PAMPA proved to provide suitable barrier properties as there was significant difference between the apparent permeability (Papp) of probes in the empty and PAMPA wells of the experiments. Further work will be carried out with PAMPA using higher glycerol concentrations (>5% v/v) as minimal effect on permeability was observed at concentrations up to 2% v/v in the PAMPA.