A rabbit model for sublingual drug delivery: Comparison with human pharmacokinetic studies of propranolol, verapamil and captopril

A rabbit model for investigating sublingual drug absorption was established yielding results consistent with clinical data reported in the literature. Using propranolol as a model compound the effect of formulation and dosing variables was explored as a means to characterize the limiting parameters...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2006-01, Vol.95 (1), p.37-44
Main Authors: Dali, Manisha M., Moench, Paul A., Mathias, Neil R., Stetsko, Paul I., Heran, Christopher L., Smith, Ronald L.
Format: Article
Language:English
Subjects:
absorption
Administration, Sublingual
Animals
bioavailability
Biological and medical sciences
buccal
Captopril - administration & dosage
Captopril - blood
Captopril - pharmacokinetics
Chromatography, High Pressure Liquid
formulation
General pharmacology
Humans
Hydrogen-Ion Concentration
Medical sciences
Models, Animal
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Propranolol - administration & dosage
Propranolol - blood
Propranolol - pharmacokinetics
rabbit model
Rabbits
sublingual
Verapamil - administration & dosage
Verapamil - blood
Verapamil - pharmacokinetics
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Summary:A rabbit model for investigating sublingual drug absorption was established yielding results consistent with clinical data reported in the literature. Using propranolol as a model compound the effect of formulation and dosing variables was explored as a means to characterize the limiting parameters of this model. In addition, verapamil and captopril were selected as reference compounds to compare this model to sublingual absorption in humans. Rabbits were dosed sublingually and systemic absorption was measured over time. Sublingual absorption of propranolol was dependent on dosing solution pH and volume. Intra-oral spray device did not affect the overall exposure compared to instillation using a syringe. Despite species and dosing regimen differences the relative bioavailabilities of propranolol and verapamil were very similar in rabbits and humans. In contrast, captopril absorption from the sublingual cavity of rabbits was low and did not agree with that observed in man. Here we report a sublingual rabbit model of drug delivery and its potential utility in preclinical development of intra-oral dosage forms. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.20312