In vitro, ex vivo  and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and Göttingen minipigs

René Holm; Emil Meng-Lund; Morten B.  Andersen; Mads L. Jespersen; Jens-Jacob Karlsson; Mats Garmer; Erling B. Jørgensen; Jette Jacobsen

doi:10.1016/j.ejps.2013.02.024

In vitro, ex vivo and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and Göttingen minipigs

René Holm, Emil Meng-Lund, Morten B. Andersen, Mads L. Jespersen, Jens-Jacob Karlsson, Mats Garmer, Erling B. Jørgensen, Jette Jacobsen

34 Citationer (Scopus)

Abstract

This work studied the buccal absorption of metoprolol in vitro, ex vivo and in vivo as a function of buffered pH at 7.4, 8.5, 9.0 and 9.5. Permeability studies showed a correlation (r(2)=0.92) between in vitro TR146 cell culture and ex vivo porcine buccal mucosa in a modified Ussing chamber. A higher apparent permeability was observed at higher pH values, i.e. the more compound that was unionised the higher the permeability. In vivo studies were conducted in anaesthetised Göttingen mini-pigs. A clear influence of pH on the absorption was seen and a significant higher absolute bioavailability was obtained after buccal dosing (58-107%) compared to oral (3%) administration, ranging 58-107% and 3%, respectively. Macroscopically, no local toxic effects were observed by visual inspection of mini-pig cheeks. A very clear level C in vitro in vivo correlation (r(2)=0.98) was obtained between the observed in vitro permeabilities and the bioavailability observed in vivo, suggesting that the two in vitro models have good predictive power for drug delivery, which could be a useful tool for future formulation developments intended for buccal delivery.

Originalsprog	Dansk
Tidsskrift	European Journal of Pharmaceutical Sciences
Vol/bind	49
Udgave nummer	2
Sider (fra-til)	117-124
ISSN	0928-0987
DOI	https://doi.org/10.1016/j.ejps.2013.02.024
Status	Udgivet - 13 maj 2013

Adgang til dokumentet

10.1016/j.ejps.2013.02.024

Citationsformater

Holm, R., Meng-Lund, E., Andersen, M. B., Jespersen, M. L., Karlsson, J.-J., Garmer, M., Jørgensen, E. B., & Jacobsen, J. (2013). In vitro, ex vivo and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and Göttingen minipigs. European Journal of Pharmaceutical Sciences, 49(2), 117-124. https://doi.org/10.1016/j.ejps.2013.02.024

In vitro, ex vivo and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and Göttingen minipigs. / Holm, René; Meng-Lund, Emil; Andersen, Morten B. et al.
I: European Journal of Pharmaceutical Sciences, Bind 49, Nr. 2, 13.05.2013, s. 117-124.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Holm, R, Meng-Lund, E, Andersen, MB, Jespersen, ML, Karlsson, J-J, Garmer, M, Jørgensen, EB & Jacobsen, J 2013, 'In vitro, ex vivo and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and Göttingen minipigs', European Journal of Pharmaceutical Sciences, bind 49, nr. 2, s. 117-124. https://doi.org/10.1016/j.ejps.2013.02.024

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abstract = "This work studied the buccal absorption of metoprolol in vitro, ex vivo and in vivo as a function of buffered pH at 7.4, 8.5, 9.0 and 9.5. Permeability studies showed a correlation (r(2)=0.92) between in vitro TR146 cell culture and ex vivo porcine buccal mucosa in a modified Ussing chamber. A higher apparent permeability was observed at higher pH values, i.e. the more compound that was unionised the higher the permeability. In vivo studies were conducted in anaesthetised G{\"o}ttingen mini-pigs. A clear influence of pH on the absorption was seen and a significant higher absolute bioavailability was obtained after buccal dosing (58-107%) compared to oral (3%) administration, ranging 58-107% and 3%, respectively. Macroscopically, no local toxic effects were observed by visual inspection of mini-pig cheeks. A very clear level C in vitro in vivo correlation (r(2)=0.98) was obtained between the observed in vitro permeabilities and the bioavailability observed in vivo, suggesting that the two in vitro models have good predictive power for drug delivery, which could be a useful tool for future formulation developments intended for buccal delivery.",

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AU - Andersen, Morten B.

AU - Jespersen, Mads L.

AU - Karlsson, Jens-Jacob

AU - Garmer, Mats

AU - Jørgensen, Erling B.

AU - Jacobsen, Jette

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N2 - This work studied the buccal absorption of metoprolol in vitro, ex vivo and in vivo as a function of buffered pH at 7.4, 8.5, 9.0 and 9.5. Permeability studies showed a correlation (r(2)=0.92) between in vitro TR146 cell culture and ex vivo porcine buccal mucosa in a modified Ussing chamber. A higher apparent permeability was observed at higher pH values, i.e. the more compound that was unionised the higher the permeability. In vivo studies were conducted in anaesthetised Göttingen mini-pigs. A clear influence of pH on the absorption was seen and a significant higher absolute bioavailability was obtained after buccal dosing (58-107%) compared to oral (3%) administration, ranging 58-107% and 3%, respectively. Macroscopically, no local toxic effects were observed by visual inspection of mini-pig cheeks. A very clear level C in vitro in vivo correlation (r(2)=0.98) was obtained between the observed in vitro permeabilities and the bioavailability observed in vivo, suggesting that the two in vitro models have good predictive power for drug delivery, which could be a useful tool for future formulation developments intended for buccal delivery.

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