TY  - THES
T1  - Combined assessment of dissolution and epithelial permeability of solid oral dosage forms
A1  - Motz,Stephan
Y1  - 2007/03/01
N2  - Assessing dissolution and Caco-2 permeability to estimate the in vivo performance of solid oral dosage forms is done since decades. However, permeability assays applying Caco-2 monolayers exhibit the drawback that, in contrast to dissolution testing, a complete dosage form is not eligible for conventional epithelial permeability assays. Hence, an apparatus was developed providing the possibility to assess permeability of solid oral dosage forms based on combination of a Caco-2 monolayer and a flow through dissolution cell. Combination of the dissolution and permeation module was performed using a depressurized stream splitter. Experiments with varying propranolol HCl tablets yielded plausible and conclusive results. Furthermore, data of these experiments were used to perform computational modelling of the concentration time trends within the apparatus. In order to increase throughput and to decrease manpower, the apparatus was automated by means of sequential injection technique (SIA) permitting online sampling and drug quantification. Finally, experiments with furosemide, a BCS class 4 compound, were carried out.
In summary, a novel tool for has been developed, which is able to monitor influences of excipients concomitantly on both dissolution and permeability through the small intestinal cell line Caco-2.
KW  - Permeabilität
KW  - Arzneimittel
KW  - Caco-2 Zellen
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2007/1023
ER  -