TY - THES T1 - In vitro characterization of the novel solubility enhancing excipient Soluplus® A1 - Linn,Michael Y1 - 2012/01/27 N2 - Although the oral route is preferred for drug administration due to its convenience for the patient, many new chemical entities suffer from low oral bioavailability due to poor aqueous solubility. Especially for BCS class II drugs, overcoming the limited solubility is crucial for a successful therapy. A relatively new technique in this context is the use of hot melt extrusion for the production of fast dissolving solid solutions. This thesis focuses on the novel excipient Soluplus®, combining solubilization and the ability to form solid solutions by hot melt extrusion in one molecule. The potency of different formulations to improve the bioavailability of BCS class II drugs was evaluated in the Caco-2 cell culture model. An excellent correlation between in vitro transport across cells and in vivo studies in dogs was found. As many solubilizers can modulate active transporters, Soluplus® was tested in Caco-2 cells for a possible interaction with the P-glycoprotein efflux system. An efflux inhibition by Soluplus® at comparably high effective concentrations was found. Uptake studies in MDCK II cells validated these results. Furthermore, the mechanism of interaction between Soluplus® and model drugs was studied, allowing the optimization of formulations with regards to drug/excipient ratios. There is a window of ratios with maximal transport rates across Caco-2 cells, as result of an interplay between solubilization, binding of drug to Soluplus® and the amorphous state of the drugs. KW - Micelle KW - Löslichkeit KW - Formulierung KW - Pharmazeutischer Hilfsstoff KW - Pharmazeutische Technologie CY - Saarbrücken PB - Universitäts- und Landesbibliothek AD - Postfach 151141, 66041 Saarbrücken UR - http://scidok.sulb.uni-saarland.de/volltexte/2012/4551 ER -