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The following message was posted to: PharmPK
Dear All,
We are trying to develop descriminstory controlled release method
for paclitaxel formulation.We are unable to maintain sink
conditions because paclitaxel is insoluble in water and also in
presence of heigher concentration than cmc level of well known
various surfactants.
Please suggest us -
-Acceptable medium in which sink condition may be possible.
-Can we used 10% or 20% ethanol in our medium.
regards
Dr Pradeep Sharma,
Mumbai(MS),INDIA
[Would a layer of organic liquid work (density > 1) ? - db]
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The following message was posted to: PharmPK
Dear Dr.Pradeep,
It sounds from your mail that you are in process of developing a
discriminatory method of controlled release injectable formulation of
Paclitaxel.
Paclitaxel is so poorly soluble that the normally recommended
concentration of the surfactants will not be enough to maintain the
sink conditions ( avialable IV injection contains almost 45% Cremophor
and 50% ethanol).The use of solvents like Ethanol can be considered
herein and it does find mention in FDA guidelines as well.Please be
alert of the fact that paclitaxel degrades very fast in aqueous media.
Its advisable for you to develop profiling on flow through appratus (
appratus IV )wherein you can get better predication of sink conditions.
I hope this helps,
Kind regards,
Pradeep S. Bhadauria
Research Scientist,
RANBAXY RESEARCH LABORATORIES.
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The following message was posted to: PharmPK
Dear sir,
Thanks a lot for responding, we are able to achieve 0.04 mg/ml
solubility of Paclitaxel in 4% Cremophore & 3% T.80 in PBS,pH-7.
Is 3% more than solubility lavel is acceptable for parentaral to
maintain sink conditions ?
Thanks again with regards,
Pradeep sharma
Research Scientist,
Wockhardt research center, Aurangabad(India)
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Dear Pradeep,
This is the major problem with all work reported on controlled release
of paclitaxel - the lack of sink condition makes it difficult to
interpret release results. I suggest if your carrier is not soluble in
organic solvent, use the 'overlay' method that you have alluded to. If
it is, have you tried using vitaminE TPGS surfactant to solubilise the
paclitaxel, or vitaminE (tocopherol) as your 'solvent' layer? Using
water soluble solvents is not advisable.
Lastly consider whether you should realistically expect a sink
condition on administration - what is the point of conducting your in
vitro work in a configuration which will not reflect in vivo conditions.
Good luck!
Ben.
Ben Boyd - Senior Formulation Scientist
MaynePharma - Proprietary Injectable Product Development Group
2/27 Laser Dve, Rowville, 3178
Victoria, Australia
t: +61 3 9753 3455
f: +61 3 9753 4533
e: ben.boyd.aaa.au.maynepharma.com
ABN 70 004 327 440
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