An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
Generally, the in-vitro property is the rate or extent of drug dissolution or release while the in-vivo response is the plasma drug concentration or amount of drug absorbed. The United States Pharmacopoeia (USP) also defines IVIVC as "the establishment of a relationship between a biological property, or a parameter derived from a biological property produced from a dosage form, and a physicochemical property of the same dosage form".
The main roles of IVIVC are:
- To use dissolution test as a surrogate for human studies.
- To supports and/or validate the use of dissolution methods and specifications.
- To assist in quality control during manufacturing and selecting appropriate formulations
Example of a correlation model
|This section is incomplete. This is because the information in the section about does not give sufficient information. (September 2016)|
- AbsScale: assess the deviations of points around the regression line, particularly around the last data points
- AbsBase: assess the X intercept of the regression line, i.e. does it cross at zero,zero if not you may need to use this variable for some baseline
- t_scale: assess the regression line to see if time in vitro needs to be scaled to correlate with time in vivo
- t_shift: assess the X intercept of the regression line, i.e. does it cross at zero, if not you may need to use this to account for a Lag in absorption
Fabs vs. Fdiss Plots and Levy Plots can be used to help determine which of these variables may be applicable.
- The United States Pharmacopeia. (23rd ed.). (1995). "In Vitro and In Vivo Evaluation of Dosage form < 1088>". 1824-1929. Rockville, Maryland.
- Shargel, L., and Yu, A. B. C. (1993). Applied Biopharmaceutics and Pharmacokinetics. East Norwalk, Connecticut: Appleton & Lange.
- Polli, J.E., Rekhi, G.S., Augsburger. L.L., and Shah, V.P. (1997): Methods to compare dissolution profiles and a rationale for wide dissolution specifications for metoprolol tartrate tablets. J. Pharm. Sci. 86:690-700.
- Drewe, J., and Guitard, P. (1993). "In vitro-in vivo correlation for modified-release formulations". Journal of Pharmaceutical Sciences. 82(2), 132-137.
- Marival Bermejo (2002) Dissolution Methodologies and IVIVC http://www.uv.es/~mbermejo/DissolutionC.pdf