In VivoIn Vitro Correlations

The major objective of using biorelevant dissolution methods is to establish in vivo-in vitro correlation (IVIVC) so that in vitro dissolution data can be used to predict bioavailability. The term in vivo-in vitro correlation is defined as a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. In general, the physico-chemical property or in vitro property of a dosage form is the in vitro dissolution profile. The biological property or in vivo response is the plasma concentration profile. Four correlation levels are defined in the FDA guidance (FDA, 1997b), as described below:

1. Level A: a point-to-point relationship between in vitro dissolution rate and in vivo input rate of the drug from the dosage form.

2. Level B: a comparison of the mean in vitro dissolution time to in vivo residence time or the mean in vivo dissolution time.

3. Level C: a single point relationship between a dissolution parameter (t50%, t90%, etc.).

4. Multiple-level C: a correlation that relates one or several pharmacokinetic parameters of interest to the amount of drug dissolved at several time points of the dissolution profile.

Among all levels of correlation, Level A is the most meaningful for predicting purposes, since it provides a relationship that directly links in vivo drug absorption to in vitro dissolution. This level of correlation should be valid for a reasonably wide range of values of formulation and manufacturing parameters that are essential for the drug release characteristics. This level can be used as a surrogate for in vivo performance of a drug product. Therefore, in vitro dissolution data, without any additional in vivo data, can be employed to justify a change made in manufacturing sites, raw material supplies, minor formulation modifications, strength of a dosage form, etc. However, the lower levels of correlation (B and C) are usually not very useful for regulatory purposes, and are used primarily for the development of formulation or processing procedures.

Was this article helpful?

0 0

Post a comment