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Cremophor Critical micelle concentration

Water-miscible surfactant molecules contain both a hydrophobic and hydrophilic portion, and can solubilize many poorly water-soluble drugs. Surfactants can also self-assemble to form micelles once the surfactant monomer concentration reaches the critical micelle concentration. Thus surfactants can solubilize drug molecules by either a direct cosolvent elfect or by uptake into micelles. The non-ionic surfactants in commercially available solubilized oral formulations include polyoxyl 35 castor oil (cremophor EL), polyoxyl 40 hydrogenated... [Pg.262]

Dose-dependent clearance and distribution was then later observed in a Phase 1 study in children with solid tumors (Sonnichsen et al., 1994). In a study in adults with ovarian cancer, Gianni et al. (1995) used a 3-compartment model with saturable intercompart-mental clearance into Compartment 2 and saturable, Michaelis-Menten elimination kinetics from the central compartment to describe the kinetics after 3 hour and 24 hour infusion. Now at this point one would typically assume that the mechanism for nonlinear elimination from the central compartment is either saturable protein binding or saturable metabolism. But the story is not that simple. Sparreboom et al. (1996a) speculated that since Cremophor EL is known to form micelles in aqueous solution, even many hours after dilution below the critical micellular concentration, and can modulate P-glycoprotein efflux, that the nonlinearity in pharmacokinetics was not due to paclitaxel, but due to the vehicle, Cremophor EL. This hypothesis was later confirmed in a study in mice (Sparreboom et al., 1996b). [Pg.12]


See other pages where Cremophor Critical micelle concentration is mentioned: [Pg.3335]    [Pg.320]    [Pg.120]   
See also in sourсe #XX -- [ Pg.332 ]




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