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Hello every one,
As most of the medicines are available in the form of tablets, can we
administer drugs to rodents in the form of powders if not tablets?
Such administration would be more realistic.
This would also exclude the use of solvents and control groups kept for
such solvents.
Water insoluble drugs then need not be dissolved in solvents like DMSO
which cause penetration to unwanted organs.
Arethere any guidelines for administrtion of test compounds to rodents?
Thank you
kind regards
Dr.Nandu Dhabale
Dr.Nandu Dhabale
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Probably,we can administer spherical granules of about
1 mm diameter. There is a method to administer 1 mm
glass beads to rats (for gastric emptying study) with
canula (size 12,).
Dr. Sunil bajad (Patil)
Research Associate
Department of Medical Sciences
School of Vet. Medicine
University of Wisconsin-Madison,
2015 Linden Drive west,
Madison 53706, WI,USA
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Yes, you can fill capsules (#9 rodent capsule) with your test powder
and gavage them using a modified gavage apparatus made for this
purpose. Our group has conducted few PK studies in rats using this
technique for danazol, ketoconazole and one other drug.
Shakil A. Saghir, M.S.P.H., Ph.D.
Senior Research Toxicologist
The Dow Chemical Co.
1803 Bldg., Midland, MI 48674
Phone: (989) 636-8708, Fax: (989) 638-9863
Email: ssaghir.-a-.dow.com
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Hello,
it may be quite late to answer this question but the most realistic way
to dose rodents per oral is to use suspensions.
1- because the drug is still made of particles which is relevant to
classic oral drug products
2- because the drug is suspended in an easy-to-handle vehicle (much
easier than pure powder dosing !)
3- because you will be able to take into account any dissolution issue
due to particle size for instance
One should argue that a suspension is not a tablet. But we, formulation
scientists, are confident that the tablet-to-suspension phase (e.g.
tablet disintegration) can easily be challenged by the use of relevant
delitants and other ingredients. This is not an issue in drug delivery.
The first issue is drug dissolution in the GI fluids as it conditions
its availability for absorption.
We use 0.5% methylcellulose in water as a vehicle for oral dosage forms
in rodents.
I hope this helps,
with best regards
Frederic Doc
Pfizer Global R&D
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Dear Dr.Shakil A. Saghir,
What size capsule could be used. I will be gratefull
if could send me the description the apparatus needen
for administering capsule in rodents
Thanking You.
Rabi
Mr.Rabi Sankar Bhatta
Junior Research Fellow
c/o Dr.G. K. Jain
Central Drug Research Institude,
Post Box- 173,Chattar Manzil Palace,
Lucknow (U.P)
India
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Frederic,
You are right, the first choice is something that can be used to make
homogenous suspension, like 0.5% METHOCEL which is the first choice for
us. However, sometime you get into issues where you can not make a
homogenous suspension no matter how much/long you stir/mix, in that one
can use some kind of surfactant (I have used up to 5% ethanol to
dissolve the test material) before adding METHOCEL. In other cases you
simply don't want to deliver your test material in suspension form due
to the end-point you are looking can be confounded by its use (e.g.,
size of the crystals, effect of excepients, soaking of beads before its
delivery, etc.), in those cases capsules can be used to orally deliver
the drug in rats to simulate what you want to do in humans. In my
opinion, deliver of drug using capsules in rats need to be evaluates on
the basis of the intended use and the end-point of the study design.
Hope this explanation will be helpful.
Shakil A. Saghir, M.S.P.H., Ph.D.
Senior Research Toxicologist
The Dow Chemical Co.
1803 Bldg., Midland, MI 48674
Phone: (989) 636-8708, Fax: (989) 638-9863
Email: ssaghir.at.dow.com
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Shakil,
I agree with you regarding the use of capsules. It may be relevant if
you
are running specific experiments.
My philosophy is to use a suspension when you want to have a first set
of
data in the field of ADME. But as soon as your drug seems promising
then you
have to perform further experiments including this kind of dosage forms
(capsules).
When you first solubilize your active in ethanol I suppose that it may
precipitate when you add the methocel solution, doesn't it ? Do you
check
for the physical form in this case ?
Best regards
Frederic
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Frederic,
This is how I see ADME studies need to be conducted. Regarding the use
of solvent, ethanol was completely miscible in METHOCEL at the levels
we used and the test compound was not precipitated out of the
suspension. We checked for homogeneity of the radiolabeled test
material in the suspension as well as physical form (concentration) by
LCMS, which are part of GLP guidelines.
Shakil A. Saghir, M.S.P.H., Ph.D.
Senior Research Toxicologist
The Dow Chemical Co.
1803 Bldg., Midland, MI 48674
Phone: (989) 636-8708, Fax: (989) 638-9863
Email: ssaghir.-at-.dow.com
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Dear Shakil,
Be carefull with mixing METHOCEL with ethanol. Methocel is not soluble
in Ethanol. You will need significant amout of water to keep methocel
in solution, which in turn may affect the solubility of the drug.
Regards,
Sunil Vandse
Able Labs
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