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Can anyone share toxicology experience using repeated oral
administration of an active drug in a SMEDD composed of:
Cremophor EL (30%)
Soybean oil (30%)
Maisine 35-1 (30%)
EtOH (10%)?
Animals will receive 125 microL of the above SMEDD by oral gavage
daily for 28 days.
Thanks for any information.
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The following message was posted to: PharmPK
Cremophor is a family of Emulsifying/solubilising agents obtained by
chemical derivation of Polyoxyethylene castoir Oil.
For Oral route I should suggest the use of Cremophor RH40 since it is
almost tasteless.
Toxicity depends on the type of animals. I only have the DL50 value
for rat
which is >6.4g/kg.
Thus, if we assume a similar DL50 for mice, an administration of 5ml/kg
will be suitable.
For Tox studies on Cremophor ask directly BASF which is the main
provider,
they will give you more information.
The administration of such vehicle has also to be considered to a
pharmacological point of view.
Concerning the Question mark on Ethanol, to my point of view 10% is
OK for
oral route.
Kind regard
Stephane
--
Beilles Stephane, Ph.D
Preformulation Study Manager
Fournier Pharma
42, Rue de Longvic
F-21300 CHENOVE
tel : +33 (0) 3 80 44 32 52
Fax : +33 (0) 3 80 44 32 70
s.beilles.at.fr.fournierpharma.com
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LD50 for Cremophor EL is
2.5 g/kg iv in mouse
> 6.4 g/kg po in rats
For Cremophor RH40 LD50 is
12.0g/kg iv in mouse
16.0g/kg po in rats
For Cremophor RH60
same as for RH40
References:
- Pharmaceutical Excipient Handboock
- R.C. Bravo Gonzales, J. Huwyler, F. Boess, I. Walter and B.
Bittner: In vitro investigation on the impact of the surface-active
axcipients Cremophor EL, Tween 80 and Solutol HS 15 on the metabolism
of midazolam (2004) Biopharm. Drug Dispos. Vol.25 pp 37-49
Best regards,
Elvire Fournier, Pharm.D, Ph.D.
Preformulation
Serono Pharmaceutical Research Institute
14 chemin des Aulx
1228 Plan-les-Ouates, Geneva
Switzerland
tel. +41 22 706 9829
fax. +41 22 794 6965
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)