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The following message was posted to: PharmPK
Dear All,
We have a query regarding the use of Beta cyclodextrin (BCD) as a
solubility enhancer in intravenous formulations. It is known that
BCDs form inclusion complexes, normally 1: 1 with the guest
molecule, thus improving the aqueous solubility.
Can we use a solution of this type in PK studies for absolute
bioavailability measurements especially when we are not sure of
the rate and extend of disociation of the inclusion complex
formed in vivo.
If the dissociation of the guest molecule is not spontaneous will
it affect the AUC?
Should we expect some changes in the AUC so obtained with the AUC
obtained with a solution of the drug with some solvent like DMSO
or DMSO:PEG combinations?
We will be highly obliged if somebody can help with some
suggestions.
Thanking you,
Sabarinath
SABARINATH. S
Research Fellow
Pharmacokinetics & Metabolism Division
C. D. R. I.
Lucknow-226001 INDIA
Phone No: 0522-2212411 to 18 Extn 4377/4389
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The following message was posted to: PharmPK
Dear Sabarinath:
I just happened to look at an research article, which probably answer
some,
if not all of your queries.
Reference: Usayapant,Karara and Narurkar. Pharm Res, Vol 8, No12 pg
1495-1499, 1991
Hope this helps.
Naushad M Khan Ghilzai,Ph.D.
Midwestern University Chicago College of Pharmacy
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The following message was posted to: PharmPK
Dear Sabaranitah,
as I mentioned yesterday in another mail regarding the use of
cyclodextrins
you have to consider the complexation constant that can be calculated
between your active and your cyclodextrin. If this complexation
constant is
low enough (let's say less than 10000 !) then the literature says that
you
can be confident that the active bioavailability will not be affected
by the
cyclodextrin.
Of course the dissociation of the complex could affect the PK profile at
least and probably also the AUC.
You really have to perform formulation studies before determining your
preferred formulation for a PK study. I am concerned that there are also
some issues using DMSO or PEG/DMSO as a vehicle for such studies. This
kind
of cosolvent vehicle is also supposed to affect the durg PK profile due
to
the risk of drug precipitation in the plasma compartment.
Following my personal experience I would keep concentrated on the
cyclodextrin as a first choice for your iv formulation. And I would do
preformulation studies to determine the complexation constant between
your
drug and the cyclodextrin you plan to use.
Did you consider vehicles using Tween, Solutol or Cremophor ?
Let me know if you need further information
Hope this helps
Regards
Frédéric DOC
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Hello,
Just I want to know how the dissociation constant can be calculated for
a cyclodextrin complex. If any references are available in the area I
request you to forward them to me
Regards,
Ravi Kanth Bhamidipati
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The following message was posted to: PharmPK
Dear Ravi,
Here is the reference that might help you.
Cyclodextrin/weak-electrolyte complexation: interpretation and
estimation of association constants from phase solubility diagrams.
Liu FY, Kildsig DO, Mitra AK. Pharm Res 1992 Dec;9(12):1671-2,
Here is the reference of another article that may help you.
Beta-cyclodextrin/steroid complexation: effect of steroid structure on
association equilibria.
Liu FY, Kildsig DO, Mitra AK. Pharm Res 1990 Aug;7(8):869-73
Thanks,
Azher
Azher M. Hussain, Ph.D
Post Doctoral Researcher
P450 Inhibition
Xenotech, LLC
Phone: 913 227 7172
Email: ahussain.-at-.xenotechllc.com
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