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The following message was posted to: PharmPK
hi all,
i am studying the pharmacokinetics of prepared
solid dispersions of a candidate drug given by oral
route in rats.Because of poor solubility, pure drug
was given as a suspension. Now I need to give an
equivalent drug amount(of solid dispersion). But in
the process due to enhanced solubility the drug is
going into solution(in vitro). My question is "wont
the PK parameters vary (i.e change in tmax and Ka)
because already the drug is in solution in vitro
before administration". Please let me know if there is
any other method to get PK parameters of solid
dispersions.
Thanks,
Regards,
V.N.R. Pavan Kumar Vaddady[M.Pharmacy],
Project Assistant,
Pharmacy Group,
B.I.T.S.-Pilani,
Rajasthan
INDIA 333031
email: pavankumarv.-a-.bits-pilani.ac.in
pavanbits.-a-.yahoo.co.in
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The following message was posted to: PharmPK
Dear Pavan,
you are right when writing that PK parameters should vary.
Regarding what you write I suppose that the solid dispersion was
designed to enhance the solubilization of your poorly-soluble drug.
If so, obviously the absorption process should show variations. But
this is the biopharmaceutical part that should be modified and pointed
out in the potential modification of the PK parameters. If you detail
the absorption process the modification will take place in the
dissolution event and if your drug is "insoluble" enough the absorption
is depending on the dissolution.
But you do not need to get any other method to determine the PK
parameters of the solid dispersion.
Such a study will conclude whether you need to make an effort on the
drug dosage form or not.
May I ask for details about the solid dispersion you designed ?
with best regards,
Frederic Doc
ACRITER - Drug discovery consulting
Visit our web site at : http://www.acriter-consulting.com
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The following message was posted to: PharmPK
Dear Frederic DOC,
Thanks for your prompt reply. From
whatever I understand, according to you, we need not
do PK study but a simple dissolution study would give
an idea. True, we have even performed a dissolution
study for all the prepared solid dispersions and
picked the one which showed maximum release in a short
period of time. And now in order to understand the PK
parameters of the best solid dispersion we have to go
for an in vivo study. So in this context the question
was putforth.
Drug chosen was a poorly soluble drug
whose solubility was enhanced by solid dsipersions. I
can give few details about the prepared solid
dispersions. These were prepared using different
hydrophilic polymers by different methods namely
solvent evaporation, melt extrusion and a combination
of these. The physicochemical characterisation was
done by available methods. As mentioned earlier
dissolution studies were also done.
Thanks,
with warm regards,
V.N.R. Pavan Kumar Vaddady[M.Pharmacy],
Project Assistant,
Pharmacy Group,
B.I.T.S.-Pilani,
Rajasthan
INDIA 333031
email: pavankumarv.-at-.bits-pilani.ac.in
pavanbits.-at-.yahoo.co.in
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hi,the PK parameters may vary because you are given two different
formulations (solution and suspension) PO. You have to take into
account the "in vivo" disolution process for the suspension.
Dr Guillermo Bramuglia
Profesor Adjunto
Catedra de Farmacologia,
Facultad de Farmacia y Bioquimica,
Universidad de Buenos Aires
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The following message was posted to: PharmPK
Pavan,
you might consider administration of drug powder or the solid
dispersions
filled into hard gelatin capsules if the dose is not high. Capsule
administration kits (for rats) are commercially available in US.
Ramesh Boinpally, PhD
OSI Pharmaceuticals
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The following message was posted to: PharmPK
Dear Pavan:
I do agree with Ramesh for dosing rats using PC caps. These
preclinical caps are available from Capsugel and you need to have
dosing kit to administer the caps in right place of the rats GIT. You
could fill about 12-15mg of drug having 0.5g/cc density. When you dose
powder ensure that you have control over particle size of drug powder
and also for solid dispersion. You may get difference in PK profile b/w
powder and suspn dosing depending upon the vehicle you use for the
suspn and time gap b/w preparing suspn nad dosing. THe drug may have
faster dissolution from solid dispersion but if you donot dose it
immediately, due to saturation in the vehicle drug could start
crystallising and you may see less AUC with solid dispn as compared to
micronised drug.
regards
Dr Shanthakumar TR
University of Utah
College of Pharmacy
USA
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