5 Top Tips on How to Establish IVIVC




Jean-Michel Cardot, Dept of Biopharmaceutics and Pharmaceutical Technology, University d'Auvergne, France, joins Pharma IQ to share his 5 top tips on how to establish in vitro-in vivo correlation (IVIVC).

IVIVC is a very nice tool if you want to develop new dru
gs or new formulation. Why? IVIVC is very important and very nice, but mainly because you are going to study the leading factor which is going to occur in vivo with very simple in vitro techniques and so you can try to overcome the problems and to optimise your formulation based on in vitro tests. 

To do that, you must have five very important points
in mind

First of all, you must know everything about your API (Active Pharmaceutical Ingredients) because all the formulations are centered on one API.  The important points on the API are to know what (i) is the solubility and the dissolution rate of the API in various conditions, behaviors, reproducing if it is possible the main events:  you will have it in your different  sections of the GI tract, and after (ii) the permeability - that means the ability of the API - to cross the membrane. If the limiting factor is the permeability, it’s no use to use IVIVC because it’s very hard to reproduce permeability in vitro and to overcome the permeability problem.  Even if your factor is solubility or dissolution rate of the API, you can use some tricks to increase the solubility or a dissolution rate and so it will not be any more a limiting factor in vivo.  That can be made by the help of IVIVC. 

The next thing which is very important is the formulation.  You must have a formulation which you can release on the rate that you want your API. That means that the formulation must be the limiting factor to use an IVIVC. 

If you want to
try IVIVC you have to have more than one formulation based on the same release mechanisms with very known characteristics of release mechanisms, so you can optimize this release based on the in vitro test to make IVIVC because we are going to compare, in vitro and in vivo, drugs and their characteristics and formulations.  You must have of course in vivo data that you are going to obtain with very simple bioavailability studies and after you will need more than one dissolution test.  That means the third point is to have all the data from in vivo and in vitro and to try to correlate them.

The fourth point is to try to make a relationship between the in vitro and the in vivo data.  Making this relationship, you can now
try the IVIVC and based on the in vitro data, try to reproduce the in vivo characteristic of your drugs and the in vivo plasma concentration of your drug from all the formulations that you had and will tested in vitro. 

Knowing that and knowing the mapping of
every important parameter, that means the physical chimical characteristics, the formulation characteristics, the critical quality attribute (CQA) of the formulation and of the API, you can now optimise your formulation and fix the dissolution limits that you will use.

Why is that so important?  It’s very important because now you can use your IVIVC for
optimizing your formulation, but also in some cases as a surrogate of in vivo studies, for example, if you want to introduce a new strength, if you want to modify your individual formulation, if you want to validate your scale up during the development and if you want to make post-approval changes on your formulations.

In this case you had invested some time and money during the development to establish IVIVC but you will gain this money at the end using the IVIVC and the surrogate data.  You need some in vitro data, you need the data for the physical clinical characteristics of the drugs and the data for
other department, and so IVIVC is a very good tool to have people speaking together and to create a spirit within the company.

So I think that is the most important point that I just said now on the IVIVC
is the interests of the IVIVC development, but also in the interests of the IVIVC on post-approval changes and a surrogate data.

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