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Dear Users
I'd like to get some feedback on suitable approaches to modelling in-vivo dissolution (with a view
to comparing it to the in-vitro performance of a formualtion), but not necessarily fraction
absorbed/oral bioavailability etc. Is this feasible and/or possible with software like
Simcyp/Gastroplus or WNL?
Many thanks and I look forward to your replies
Steve
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Hi Steve
I guess the short answer is yes you can; of course as long as the models that you use have the
capability of separating different processes happening during absorption and first pass disposition.
This was the topic of discussion at a session at the AAPS meeting last month in San Diego and you
can see more details by visiting:
https://2014aapsam.zerista.com/event/member/124150
Hope this is useful.
Regards
Masoud
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Dear Steve,
Classical theories of dissolution (eg. Nernst-Brunner, Wang-Flanagan, or more advanced mass
transfer models that consider hydrodynamics, and slip velocity) work well to predict the relatively
simple in vitro dissolution (in a USP apparatus) of immediate release formulations when the
influence of drug solubility, particle size distribution, particle density, diffusion coefficient,
media constituents (buffers and surfactants), and microclimate pH can be integrated dynamically
(Almukainzi M, Okumu A, Wei H, Löbenberg R. AAPS PharmSciTech. 2014 Nov 20. [Epub ahead of print]
PMID: 25409918).
Simulating in vivo dissolution is obviously more complex due to the influence of changing fluid
volumes, pH, bile salt concentrations, and absorption effects on sink conditions in the small
intestine and colon. Many of these factors are considered in the mechanistic dissolution and
absorption models found in software like GastroPlus and SimCYP. These models are based on theories
that by definition cannot be as sophisticated as the in vitro dissolution models due to the many
known unknowns of buffer composition and in vivo hydrodynamics which are completely different than
in vitro (Wang, et al., 2010 A Multi Scale Lattice Boltzmann Model of Macro- to Microscale
Transport, with Applications to Gut Function. Phil Trans R. Soc A 368: 2863-2880). However, the
practical experience of thousands of users for more than a decade have proven that the in vivo
mechanistic oral absorption models are useful and predictive in formulation design, development, and
clinical performance. So as Masoud said, the short answer is yes, you can directly compare simulated
in vivo dissolution to experimental or simulated in vitro dissolution using the software you
mentioned.
Give them a try,
Mike
Michael B. Bolger, Ph.D.
Chief Scientist
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Steve, as others have already commented both SimCYP and Gastroplus can support this with a
physiological basis, however sometimes you might not have the information you need to make the
correct assumptions and the IVIVC toolkit from WNL might be a good alternative if you have some in
vivo data to build a correlation model with; www.certara.com/products/pkpd/ivivc
There are some short high-level YouTube videos on this kit e.g.
https://www.youtube.com/watch?v=-AYnWrWsAXo
As well as some more references by searching for ivivc on
http://www.certara.com/resource-library/results/query/
Or indeed these older webinars;
http://www.pharsight.com/events/eventsonline_archive.php#replay_015
http://www.pharsight.com/events/eventsonline_archive.php#replay_048
Best regards,
Simon.
--
Simon.Davis.at.certara.com
Senior Scientific Consultant
Pharsight- A Certara™ Company
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