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The following message was posted to: PharmPK
Could someone advise me on whether to use water or saline when using
cremophor or polysorbate 80 in iv dosing of rodents?
Thanks in advance
Leslie
Leslie D. Jones, RALAT
Research Scientist I
ICAgen Inc
4222 Emperor Blvd. Ste. 390
Durham, NC 27703
Billing:
P.O. Box 14487
Research Triangle Park, NC 27709
Phone: 919-941-5206
Direct: 919-281-5513 ext. 553
Fax: 919-941-0813
[The solution should be isotonic, correct? - db]
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The following message was posted to: PharmPK
My opinion is to use some phosphate buffer to get a relevant and stable
pH of your iv dosing solution. This will avoid any pH variation due to
your active for instance.
We generally use PS80 or Cremophor at 2.5% in pH7.4 phosphate buffer.
Does make sense
Regards
Frederic Doc
Pfizer Global R&D
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I agree with Frederic. One may also explore the use of cosolvents along
with surfactants such as PS80, Cremophor. Propylene glycol,
polyethylene glycol 400 are some I have used. If the drug is
hydrophobic, you may have to set up a series of experiments varying the
ratio of Surfactant to Coslovent as well as total concentration
required to solubilise the drug. One should also ensure that drug does
not precipitate after dilution.
Regards,
Sunil V
Abke Labs
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I been using saline
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Dear sir,
but what about water insoluble drugs.
Dr.Nandu
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Hello,
we are all handling roughly insoluble drugs. This is why we are
existing. But I would recommend that if your drug cannot be formulated
in surfactant or cyclodextrin solutions then you should be the first
person to ask for stopping further work on such chemicals. What I
suggest is that this kind of materials should quickly raise issues in
preclinical experiments (variability in terms of absorption, ADME
parameters, pharmacological response in in vivo models).
This is also part of our mission to alert discovery scientists when we
are truly confident that we and they are wasting time working on
chemicals that will fail in the future.
Best regards,
Frederic Doc
Pfizer Global R&D
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The following message was posted to: PharmPK
Hello,
we are all handling roughly insoluble drugs. This is why we are
existing. But I would recommend that if your drug cannot be formulated
in surfactant or cyclodextrin solutions then you should be the first
person to ask for stopping further work on such chemicals. What I
suggest is that this kind of materials should quickly raise issues in
preclinical experiments (variability in terms of absorption, ADME
parameters, pharmacological response in in vivo models).
This is also part of our mission to alert discovery scientists when we
are truly confident that we and they are wasting time working on
chemicals that will fail in the future.
Best regards,
Frederic Doc
Pfizer Global R&D
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Dear Frederic Doc,
Exactly at what stage of the drug discovery programme do we have to
consider the formulation issues, Since we will be dealing with large
no. of molecules?
Thanks,
B.L.Suresh
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The following message was posted to: PharmPK
I would say that you have to care about these formulation issues as
soon as possible. We care about this at the stage of lead optimization.
As soon as you have chosen your chemical series chemists will
synthesize derivatives with different physical chemical properties.
We have developed an automated method to set up IV formulations based
on standard vehicles including surfactant and cyclodextrin solutions.
The fact is that if no formulation can be set up with these standard
vehicles we have to alert the research project teams of the risks
linked to the solubility issue. And just because we are at an early
stage of drug discovery we can drop compounds or just consider them as
back-ups to be tested after other compounds failed. This is a question
of prioritization. When you
have 10 compounds to test and you can only test 2 of them per week you
will choose the ones to be tested in priority regarding other
parameters (in vitro stability, selectivity ...and solubility in pH7.4
buffer and in IV vehicles).
I hope it helps,
best regards
Frederic Doc
Pfizer Global R&D
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