Back to the Top
We have a compound in Phase I with marked variability in apparent absorption (elimination half-life
remains quite constant).
The formulation is dry-filled capsules. Does anyone have any experience of improving absorption by
using a liquid-filled capsule?
Thanks,
Charlie
Back to the Top
Dear Charlie,
There could be many reasons for the variable absorption. You might need to check the physicochemical
properties of the compound, its bio-pharmaceutical behaviour, and of course the formulation
strategies. The observations that you have, might be related to the biopharmaceutics of the compound
or could be the related to the in-appropriate selection of formulation strategies or bit of both.
Liquid filled capsules work best if the compound is reasonably lipophilic and the mechanism of
absoprtion is more towards lipid digestion pathway. Having a look at the compound might throw some
light.
Kindly contact .aaa. vaibhav_s.at.aurigene.com for me to understand more in detail about the issues you
might be facing and if possible, can it be sorted out in a quick time manner.
regards
--
Vaibhav Sihorkar, Ph.D.
Sr. Group Leader, Pharmaceutical Development
Back to the Top
Hi Vaibhav,
The compound is highly lipophilic (log P = 4.45) and would be expected to undergo at least some
lymphatic absorption.
I would anticipate, as you suggest, that a liquid-filled capsule would provide better absorption
properties than dry-filled.
I was looking for some examples of where this occurred....
Thanks,
Charlie
Back to the Top
Dear Charlie
Prior conducting lipidic formulation it is important to master the mechanism of absorption together
with the full characterization of physicochemical parameters : ionization state as a function of pH
values found in the GI tract (see Boisset et al Eur J Pharmaceutical Sci; 2000), Log P, dissolution
rate, efflux etc... This will help you to define the formulation strategy.
If necessary, the lipidic based formulation can be a good strategy to overcome both variability
issues and low bioavailability issues. Caco-2 cell monolayers can be used to select the most
promising lipidic based formulation (see WO 2006/01 8501 A1, Jean Pachot et al). Don't hesitate to
revert to me if needed.
Warmest regards
Jean
Jean PACHOT, President & CSO
Oroxcell SAS
www.oroxcell.com
Parc technologique Biocitech
102, Avenue Gaston Roussel
F-93230, Romainville
jean.pachot.-a-.oroxcell.com
|
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@lists.ucdenver.edu with "Bioavailabiliy dry powder vs suspension" as the subject |
Copyright 1995-2014 David W. A. Bourne (david@boomer.org)