Int J Pharm
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark. Electronic address:
Published: November 2019
In the small intestine, P-glycoprotein (P-gp) may limit the permeability of its substrates, which lead to reduced oral absorption. To circumvent the effect of P-gp, a nanocomposite material termed montmorillonite-surfactant hybrid particles was developed. The particles consisted of montmorillonite, the P-gp-inhibiting, nonionic surfactant, polysorbate 20, and the P-gp substrate, digoxin. The present study aimed to investigate if montmorillonite-surfactant hybrid particles could modulate the absorption of digoxin in vivo. Montmorillonite-surfactant hybrid particles were prepared by lyophilising an aqueous suspension of the constituents. Scanning electron microscopy, thermogravimetric analysis, and powder X-ray diffraction revealed an altered surface morphology, decreased water content, and intercalation of polysorbate 20 between montmorillonite layers. The particles were administered orally to Sprague Dawley rats, and digoxin was quantified by liquid chromatography-tandem mass spectrometry. Control digoxin-containing montmorillonite decreased the exposure of digoxin. In contrast, montmorillonite-surfactant hybrid particles increased AUC and C by 31 and 91%, respectively, compared to digoxin in solution. It was hypothesised that montmorillonite-surfactant hybrid particles increased digoxin exposure by forming mucosa-localised elevated concentrations of polysorbate 20 and digoxin, which enhanced the inhibitory effect of polysorbate 20 on P-gp.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118696 | DOI Listing |
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