Cremophor

Ethoxylated castor ods or ethoxylated castorwaxes are used as solubilizers of hydrophobic substances in cosmetics. Examples are Cremophor EL (ethyoxylated castor od) and Cremophor RH (40/60 ethoxylated hydrogenated castor od). Other ethoxylated triglycerides are not as effective as castor od. Ethoxylated castor od is also a good solubilizer for vitamin A palmitate (121). 

Hypnotics. Common hypnotics are thiopental, propofol, midazolam, etomidate, ketamine and inhaled anesthetics. The incidence of hypersensitivity reactions with thiopental is rare. Recently, thiopental was involved in less than 1% of allergic reactions in France [9]. Ever since Cremophor EL, used as a solvent for some non-barbiturate hypnotics, has been avoided, many previously reported hypersensitivity reactions have disappeared. In the last French surveys, reactions to propofol accounted for less than 2.5% of allergic reactions, and reactions to midazolam, etomidate or ketamine appear to be really rare [9]. Finally, no immune-mediated immediate hypersensitivity reaction involving isoflurane, desflurane or sevoflurane has been reported despite their wide use. 

Medicinal chemists should be aware that inexperienced biologists can erroneously conclude that poorly aqueous soluble compounds are orally absorbed when compounds are dosed in pharmaceutically unacceptable solvents. Always ask what is the dosing vehicle Heroic combinations of DMSO, Cremophor, poly(ethylene glycol), Tween-80 and ethanol are unacceptable and misleading. In case of doubt consult with a pharmaceutical scientist colleague. The reliable standards are an aqueous solution (with perhaps a trace of DMSO) or a suspension (perhaps stabilized with an acceptable quantity of adjuvant, e.g. Tween-80). 

Ring systems intermediate between phthalocyanines and naphthalocyanines are known 263,264 (51) is such a compound. They are most simply called benzonaphthoporphyrazines, and various zinc(II) complexes with cationic (A--m e t hy 1 pyridini um-3-oxy) substituents have Amax in the range 680-750 nm in solution or in Cremophor micelles, and show promise in bioassays in vivo.264... 

The photodynamic effect of chloroaluminum(III) phthalocyanine ((47), with C1A1 in place of Zn), a commercial product, was reported by Ben-Hur and Rosenthal.302 The photosensitizer was delivered in ethanol to cultures of Chinese hamster fibroblasts. After equilibration (16 h), exposure to visible light (fluence rate 64 Wm-2) of a suspension in PBS for 2 min gave a 3 log kill. Lack of water solubility is a problem, and for in vivo PDT of EMT-6 mammary tumors in mice a Cremophor emulsion was employed.303 The compound was a more effective PDT sensitizer than... 

The axial chloride ligand of ClAlPc is readily replaced by hydroxide (H20-NH3-Py, 4h, A), and other axial ligands can then be attached (e.g., trihexylsiloxy-, cholesteryloxydiphenylsiloxy-). In in vitro assays (M6 melanocytes) these compounds (lecithin or Cremophor delivery) were more effective PDT agents than ClAlPc.241... 

The bis(jS-diketonato) Ti(IV) complex [Ti(bzac)2(OEt)2] 35 (budoti-tane, shown as the predominant cis,cis,cis isomer) entered phase I clinical trials in Germany in 1986 for the treatment of colon cancer (186). The complex is very susceptible to aquation, and to minimize this, the coprecipitate (Cremophor EL, 1,2-propylene glycol in ethanol and 35) is dissolved in water prior to administration. As for titano-cene dichloride, liver damage is the dose-limiting side-effect (187). The activity of this class of complexes shows little dependence on the nature of the leaving group (e.g., OEt, Cl), but aromatic substituents... 

Subsequently, we expanded on these efforts by studying the effects of various formulations, routes, and schedules of i.v. administration. We discovered that slow infusion (6 h, Q2D, 30 mg/kg x 5 doses) of dEpoB in nude mice bearing human xenograft tumors with a Cremophor-ethanol vehicle was the most beneficial in terms of efficacy and decreased toxicity. 

Rege and colleagues have studied the effect of nonionic surfactants (e.g., Cremophor EL, Tween 80, and TPGS) on membrane transporters [116], Similar results for vitamin E TPGS using talinolol and rhodamine 123 as P-gp substrates have been reported by Bogman et al. ([32] and Collnot and coworkers [40], respectively. 

Rather than using the initial donor concentration, the final donor concentration at the termination of incubation can be used. Another approach to reduce nonspecific binding involves the addition of serum proteins [80, 120] or micelleforming excipients, such as Gelucire 44/14, Cremophor EL, or TPGS, [45] to the receiver compartment, leading to an improved assay recovery and better predictability of the model [64],... 

Seeballuck F, Ashford MB, O Driscoll CM (2003) The effects of Pluronic block copolymers and Cremophor EL on intestinal lipoprotein processing and the potential link with P-glycoprotein in Caco-2 cells. Pharm Res 20 1085-1092... 

The story of the 331 patent is complex. It claims priority back to an original application filed in 1993, seven years before its issuance. The majority of the claims in the patent cover taxol substantially free of cremophor, the solvent used for dissolving and administering the FDA-approved version of taxol. Hence, these claims do not cover the approved version of taxol and caimot support listing. However, a small number of broad claims recite a vessel containing a specified amount of a taxol ranging from 33 mg to 3000 mg. These claims arguably cover, for instance, a bag for intravenous administration of taxol as approved by the FDA, but a district court has also invalidated the claims based on this interpretation. ... 

Both drugs are highly lipid soluble and as such are prepared and administered in dilutants (paclitaxel in Cremophor EL and docetaxel in polysorbate 80). Both medications are normally administered with dexamethasone, H, and H2 antagonists as premedications to decrease the incidence of the acute hypersensitivity reaction (HSR) (dyspnea with bronchospasm, urticaria, and hypotension) that has been observed to occur... 

Drugs formulated with Cremophor EL (Althesin, propanidid, propofol EL)... 

Excipients offer several possibilities and mechanisms. For microemulsions, Cremophor RH 40, Cremophor EL, and Solutol HS 15 act as surface active solubilizers in water and form the structures of micelles. The micelle that envelops the active substance is so small that it is invisible, or perhaps visible in the form of opalescence. Typical fields of application are oil-soluble vitamins, antimycotics of the miconazole type, mouth disinfectants (e.g., hexiditin), and etherian oils or fragrances. Solutol HS 15 is recommended for parenteral use of this solubilizing system and has been specially developed for this purpose. 

Active substances can also be solubilized by Lutrol F 68 in addition to the Cremophor and Kollidon products. The... 

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