Permeation studies on freshly excised rat gastric mucosa: influence of pH.
The objective of this study was to evaluate the influence of pH on the permeation of model drugs through freshly excised rat stomach. Additionally, the capability of excised gastric mucosa to maintain an acidic pH was assessed. In vitro permeation studies were performed in Ussing-type diffusion chambers with rat stomach using fluorescence-labeled bacitracin (bac-FITC), sodium fluorescein (NaFlu), propranolol HCl, and cimetidine as model drugs. The pH was adjusted to pH 1, 2, and 6.8 in the donor chamber and pH 7.4 in the acceptor chamber. The study demonstrated that both, the fore stomach and the glandular gastric mucosa, are capable of maintaining an acidic pH of 1-1.2 in the donor chamber. P(app) (permeation coefficients) were found to be 1.4 ± 0.6 ×·10(-7) and 7.6 ± 0.7 ×·10(-7) for bac-FITC and 3.3 ± 1.5 ×·10(-7) and 2.4 ± 0.6 ×·10(-6) cm/sec for NaFlu at pH 2 and 6.8, respectively, in the glandular stomach. In order to evaluate the effect of pH on the integrity of paracellular space, propranolol as high-permeability drug and cimetidine as low-permeability drug were chosen. The P(app) of propranolol HCl was determined to be 5.9 ± 0.3 ×·10(-7) and 1.1 ± 0.7 ×·10(-6) cm/sec at pH 2 and 6.8, respectively, in the glandular stomach. Cimetidine showed a permeability of 1.4 ± 0.4 ×·10(-5) and 9.6 ± 2.3 ×·10(-6) cm/sec at pH 2 and 6.8. Results provide essential basic information for the development of gastric drug delivery systems.
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Innsbruck, Austria/Europe.
Katharina
K
Leithner
Vjera
V
Grabovac
Karin
K
Albrecht
Juliane
J
Hombach
Günter
G
Klima
Andreas
A
Bernkop-Schnürch
D000818:Animals; D001414:Bacitracin / Q000494:pharmacology*; D002927:Cimetidine / Q000493:pharmacokinetics; D019793:Fluorescein / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D010539:Permeability; D010599:Pharmacokinetics; D011433:Propranolol / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D001414:Bacitracin; D002927:Cimetidine; D011433:Propranolol; D016650:Fluorescein-5-isothiocyanate; D019793:Fluorescein