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 Citations (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.

Original language	Danish
Journal	European Journal of Pharmaceutical Sciences
Volume	49
Issue number	2
Pages (from-to)	117-124
ISSN	0928-0987
DOIs	https://doi.org/10.1016/j.ejps.2013.02.024
Publication status	Published - 13 May 2013

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10.1016/j.ejps.2013.02.024

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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.
In: European Journal of Pharmaceutical Sciences, Vol. 49, No. 2, 13.05.2013, p. 117-124.

Research output: Contribution to journal › Journal article › Research › 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, vol. 49, no. 2, pp. 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.

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