title: Novel poloxamer-based nanoemulsions to enhance the intestinal absorption of active compounds.
abstract: On the basis of Pluronic P104 as primary emulsifier and Lauroglycol 90 as amphiphilic oil phase, two nanoemulsion systems were developed with Pluronic((R)) L62 or L81 as secondary emulsifiers. The possible nanoemulsion region of combinations of these excipients was described in ternary phase diagrams. Three formulations were selected from the nanoemulsion region and their potential impact on oral absorption was examined in the Caco-2 monolayer model of the small intestine. The apparent permeability of the BCS class III compound Atenolol was enhanced 2.5-fold, of BCS class II compound Danazol 3.2-fold and of BCS class I compound Metoprolol 1.4-fold. The three formulations were very well tolerated by the Caco-2 cells, which was confirmed by TEER measurements, a MTT test and a LDH release test.
authors.affiliation: Schering AG, Pharmaceutical Development, Berlin 13342, Germany. carsten.bruesewitz@schering.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Brüsewitz
authors.forename: Andreas
authors.initials: A
authors.lastname: Schendler
authors.forename: Adrian
authors.initials: A
authors.lastname: Funke
authors.forename: Torsten
authors.initials: T
authors.lastname: Wagner
authors.forename: Ralph
authors.initials: R
authors.lastname: Lipp
mesh_terms: D018938:Caco-2 Cells; D003613:Danazol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004655:Emulsions; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D050997:Nanomedicine; D010316:Particle Size; D020442:Poloxamer
chemical_list: D004655:Emulsions; D004965:Estrogen Antagonists; D020442:Poloxamer; D003613:Danazol