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Hello,
For an experimental compound intended for oral dosing in rats, two
formulations were prepared: a suspension and solution in a Miglyol 810
(a lipophilic vehicle). The two formulation were orally administered to
rats at a dose volume of 4 mL/kg. PK analysis demonstrated that the
relative bioavailability in Miglyol was approximately 20% that of the
aqueous suspension.
In your opinion, was the dosage volume used in the study in excess
thereby substantially limiting absorption (the loss of drug in feces
was not evaluated)? If so, what are the recommended volumes to be
administered to rats and the means/techniques to do so? Guidance to
appropriate references is welcomed.
Regards,
Ofer
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The following message was posted to: PharmPK
Hello,
first I would like to take this opportunity to wish a happy new year to
all of you.
Secondly about your experiment I would say that the difference in PK
data between both formulations is due to the lipophilicity of your
active.In a large amount of lipophilic vehicle (it was 4 mL/kg of pure
Miglyol, wasn't it ?) your drug did not move to the hydrophilic
compartment (e.g. GI secretions). In my mind I would conclude that
there was a dissolution limiting factor that led to an apparent loss of
absorption.
My recommendation is to use the suspension as a reference formulation
for the oral route.
Regarding the use of Miglyol my group also uses it (when absolutely
necessary !) but only to create microemulsions at concentrations up to
5% in an aqueous vehicle (0.5% methylcellulose in water). The drug is
solubilized in the Miglyol and then we add the metylcellulose aqueous
solution and we stir before doing some sonication to make the
microemulsion.
I hope this helps,
Frederic Doc
Preformulation group
Pfizer Global R&D (still for a couple of weeks)
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)