Novel poloxamer-based nanoemulsions to enhance the intestinal absorption of active compounds.
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.
Brüsewitz
Carsten
C
Schering AG, Pharmaceutical Development, Berlin 13342, Germany. carsten.bruesewitz@schering.de
Schendler
Andreas
A
Funke
Adrian
A
Wagner
Torsten
T
Lipp
Ralph
R
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
D004655:Emulsions; D004965:Estrogen Antagonists; D020442:Poloxamer; D003613:Danazol