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The following message was posted to: PharmPK
Dear all,
I need to perform an absolute bioavailability study
(i.v. verus p.o.) in rats with an NCE which is
water-insoluble (soluble in acetonitrile and
methanol).
Could anyone suggest a vehicle I could use in order to
administer the compound intravenously? I believe
PEG400 can be used up to a concentration of 4% but I'm
not sure my compound will remain in solution after
diluting the PEG solution with physiological buffer.
Thanks,
Jasmine Davda.
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Jasmine
You could try 5% cremaphor/ 5%ethanol in saline or glucose.
If the compound 'crashes out' when you add the aqueous phase, you may
want to substitute with 20% 2-hydroxy propyl beta cyclodextrin.
Substituting the aqueous phase with cyclodextrin makes your solution
viscous, so I'd take care when dosing.
Good luck
Chris Liddle
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The following message was posted to: PharmPK
Dear Jasmine
Try the following
DMA 20 - 30% PEG 400 20 - 30% qs 0.9% saline. DMA = N, N-dimethyl
acetamide.
I utilized these formulations for product with lipophilicity approx. 4
with
success in 300-g rats (injected iv volume: 0.5 - 1.0 mL).
The formulation is no tolerated by the mice.
Best wishes
Bernard Ludwig, PhD, CChem M.R.S.C.
ADDEX Pharmaceuticals Ltd
+41 22 884 15 82 (direct)
+41 22 884 15 55
bernard.ludwig.-at-.addexpharma.com
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Hi Jasmine, have u tried solublising a 1-2% DMSO solution of the
compound
in 20% beta cyclo dextrin solution. This is a very good approach of
solublization. However it is quite an expensive formlation. bye,
Jagannath
Kota
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The following message was posted to: PharmPK
Jasmine,
Don't forget that if you are developing NCE's aiming to treat CNS
disorders,
you should not use ethanol.
Best regards,
Bernard Ludwig, PhD, CChem M.R.S.C.
ADDEX Pharmaceuticals Ltd
+41 22 884 15 82 (direct)
+41 22 884 15 55
bernard.ludwig.at.addexpharma.com
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The following message was posted to: PharmPK
Jasmine,
if you want to use PEG400 I suggest that you ensure that no
precipitation
occurs by performing a dilution experiment in some pH7.4 buffer when
setting
up your iv formulation.
Jasmine, Chris,
I also use Cremophor or Tween 80 or Solutol HS15 in pH7.4 buffer, up to
2.5%. The use of such surfactants avoids any risk of precipitation.
If you need to use cyclodextrins (which is my second intention vehicle
for
iv formulations) you should ensure that the complexation with your
active
will not interfere in drug disposition. We use HPbCD up to 30% in pH7.4
buffer without any viscosity issue.
I hope this helps,
Frederic Doc
Pfizer Global R&D
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The following message was posted to: PharmPK
One could try 10-20% NMP (N,2-METHYL PYRROLIDINE) , Premixture
containing ratios of 1:3, 1:2, 1:1 :: PEG 200/400 : water for inj.
In case required u could try 10-20% ethanol also in these formulations
to avoid the compound precipitating out.
Regards,
KANTHI KIRAN V.S. VARANASI
Glenmark Pharmaceuticals LTD.
INDIA.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)