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Dear All,
I have a small querry,
Well, if the drug candidate is having the protein binding 90%, the dose
required in vivo is around 600mg, the drug is prone for its own metabilism
and induces others, is it a idal drug to be formulated as Sustained
release
formulation.
Is there any fixed data based on plasma protein binding and its corelation
to its formulation as sustained release.
Kindly suggest!
Prashant
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Prashant,
I don't think we can say that it's an ideal drug for sustained release (SR).
SR properties are generally obtained using specific ingredients. The trouble
is that to get the correct dissolution profile you need to adjust relative
quantities of ingredients. Oftenly the amount of ingredients is the quite
high to get the SR effect. So if you envisage an active dose of 600mg (at
least, because your SR system is supposed to deliver up to 80% of the total
dose) then you'll probably develop a 1.5g tablet which is quite large.
The solution is probably to develop some SR granules (matrix, or coated
granules) that can be dispersed or swallowed as is. This allows to enhance
the amount of drug in the formulation but you have then to deal with humans
that don't like this dosage form !!!
Best regards,
Frederic
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The following message was posted to: PharmPK Propranolol is over 90%
bound in plasma, and it has been successfully dosed as controlled
release.
Metoprolol is almost 90% bound, and it has been successfully dosed as
controlled release.
So it would seem that 90% plasma protein binding does not eliminate a
compound from being a candidate for controlled release.
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (SIMU)
1220 W. Avenue J
Lancaster, CA 93534-2902
U.S.A.
http://www.simulations-plus.com
E-mail: walt.aaa.simulations-plus.com
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Dear Colleagues,
With respect to the relationship between a 'sustained release
candidate' and '90% plasma protein binding': I don't see the
rationale for any relationship.
I would appreciate a reaction from those who expect some relationship here.
Best regards,
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
Email: j.h.proost.aaa.farm.rug.nl
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The following message was posted to: PharmPK I made an error the
other day regarding the plasma protein binding for metoprolol. Alex
Hemeryc (sp?) of Johnson and Johnson was kind enough (and tactful
enough!) to point out the error to me by private e-mail. I had looked
at a file containing percent unbound rather than percent bound. The
plasma protein binding for metoprolol is only 10-12%.
Sorry for any confusion.
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (SIMU)
1220 W. Avenue J
Lancaster, CA 93534-2902
U.S.A.
http://www.simulations-plus.com
E-mail: walt.-a-.simulations-plus.com
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