Skip to content
New issue

Have a question about this project? Sign up for a free GitHub account to open an issue and contact its maintainers and the community.

By clicking “Sign up for GitHub”, you agree to our terms of service and privacy statement. We’ll occasionally send you account related emails.

Already on GitHub? Sign in to your account

How to consider precipitation process in PK-Sim? #435

Open
wangwei1619 opened this issue Dec 18, 2019 · 4 comments
Open

How to consider precipitation process in PK-Sim? #435

wangwei1619 opened this issue Dec 18, 2019 · 4 comments

Comments

@wangwei1619
Copy link

@wangwei1619 wangwei1619 commented Dec 18, 2019

Hi, all
I am curious about how to consider precipitation process in PK-Sim. Formulation type as Weibull and table allow dissolution profile showing increasing trend, so how to handle dissolution profile like this ( citted from DOI: 10.1208/s12249-013-0018-2):
image
It is a weakly basic drug so that it easily precipitate in intestine. I have not found a parameter related to precipitation process like mean precipitation time yet. Is there any way to simulate situation like this?

@Yuri05

This comment has been minimized.

Copy link
Member

@Yuri05 Yuri05 commented Dec 18, 2019

You could try reproducing of the corresponding InVitro experiment using particles dissolution.
For this: create a simulation in PK-Sim with a Particles Dissolution Formulation and export it to MoBi.
(Start with a monodisperse formulation).

In MoBi (in the simulation):

  1. set Organism|Lumen|OralApplicationsEnabled to 0. This will deactivate all movements of drug/liquid/etc. from Stomach into Duodenum
  2. Set Organism|Lumen|Stomach|Liquid to the volume used in the inVitro experiment
  3. Set Organism|Lumen|Stomach|pH to the pH used in the inVitro experiment
    grafik
    Now you can play around with some parameters of the particles dissolution formulation and molecule properties and compare fraction dissolved with your inVitro experiment.
    Most of those parameters can be changed directly in MoBi.
    (Treat precipitated drug as and Enable supersaturation can be set either to 0 or to 1)
    grafik
    However if you would like to change number of particle bins or any formulation parameters affecting the radius distribution between particle bins: this must be done in PK-Sim and then reexport the simulation.
    grafik

@AndreDlm @KatrinCoboeken @sfrechen Any further comments on this?

@wangwei1619

This comment has been minimized.

Copy link
Author

@wangwei1619 wangwei1619 commented Dec 19, 2019

Dear @Yuri05 ,

Thanks for your comment. Do you mean I can first find porper properties of drug to simulate the in vitro dissolution profile in gastric condition, then use these parameters to do simulation in normal condition?

And how does PK-Sim condsider the precipitation process? Is it a reverse process of dissolution and using Noyes-Whitney equation too?
If so, is there any way to handle situation like this (cited from DOI: 10.1016/j.ejpb.2016.05.017)?
image
These are dissolution profiles for solid dispersion of celecoxib in 500 mL FaSSIF, and the dashed line is equilibrium solubility of crystalline celecoxib in FaSSIF. The precipitation does not happen as soon as concentration achieve the equilibrium solubility and not lead to a concentration around the equilibrium solubility in the end. Moreover, it shows that drug begin to precipitate when concentration reach the peak (I am not assure if it is named as dynamic solubility), thus there must be 2 kind of solubility value in dissolution function, but Noyes-Whitney equation only has one solubility.

I think the first issue may could be addressed by easily calculating the final equilibrium solubility of solid disperion. What about the second issue? Do I have to make change to dissolution function?

Best regards,
Wang Wei

@Yuri05

This comment has been minimized.

Copy link
Member

@Yuri05 Yuri05 commented Dec 19, 2019

Do you mean I can first find porper properties of drug to simulate the in vitro dissolution profile in gastric condition, then use these parameters to do simulation in normal condition?

Yes

And how does PK-Sim condsider the precipitation process? Is it a reverse process of dissolution and using Noyes-Whitney equation too?

Yes. For details s. e.g.

If so, is there any way to handle situation like this...?

Well, not sure if it's possible to reproduce such a dissolution profile 1:1 with the Noyes-Whitney. Using polydisperse formulation in combination with supersaturation you can achieve immediate dissolution of the part of the drug followed by slow precipitation to equilibrium (s. example attached). However it is still not exactly your case
P1_Precipitation.zip

@wangwei1619

This comment has been minimized.

Copy link
Author

@wangwei1619 wangwei1619 commented Dec 27, 2019

That's quite helpful, I'll try latter.
Thank you very much.

Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment
Projects
None yet
2 participants
You can’t perform that action at this time.