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Dear all,
I need a clarification on the following issues:
1. I am working with a highly soluble compound. When I do the
dissolution studies in various media (HCl, water, buffers with pH 4.5
and 6.8), all the formulations released the same amount of drug and
the release profile is comparable to innovator. So, how do I select
the best formulation for my in vivo studies. How do I statistically
differentiate the formulations, can I rely on any of the conventional
parameters.
2. As I am working on orally disintegrating tablets, I would like to
know regarding the dosing of the dosage form to rabbits. Can I give it
in a suspension form by suspending the whole tablet in a few ml of
water just before administration to rabbits in particular or if I have
to dose it in the form of a tablet what is the convenient method to
administer the tablet below the pharynx.
Providing the references and comments on these issues is highly
appreciable.
Thank you
Ravi Sheshala
School of Pharmaceutical Sciences
Universiti Sains Malaysia,
Penang, Malaysia
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The following message was posted to: PharmPK
Picking the least toxic formulation is a start.
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Ravi
1. First you have to observe which dissolution testing variable (could
be medium, speed, volume, or apparatus 1 or 2 or other) most has a
major impact on the cumulative drug release of your test formulation,
keeping in mind the bio-relevance. Once all variables are set then
tweaking that variable that impacts your product try matching the RLD
drug release profile. Once you are satisfied with the match go for a
BE study and do a 3 way cross over design and bracket the slow and the
fast formulations. what is the purpose for statistically
differentiating the formulations? Need more clarity here.
Hope this helps.
Manish Issar, Ph.D
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Ravi,
there are very established methods for oral gavage for animal studies,
including rabbits. You may have to cut the tablet into smaller pieces
to fit the gavage tube that you will be using. Alternately, you can
crush the table and pack it into gelatin capsules (commercially
available - rapid dissolution of the gelcaps acts in a manner similar
to a tablet) for and easier fit into the gavage tube, rinse with
saline to assure clearance and entry in to the stomach. If you're
concernmed about crushing the tablet then make a slurry in saline and
administer the particulate mixture by gavage. It may seem like a lot
of work, but tis worth it to design the right study with the right
questions bening answered. Some of the other investigators have also
provided you valuable input.
--
Sanjeev Thohan, PhD
SARx Consulting
SARxconsult.-at-.Gmail.com
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