IVIVC

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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".

Typically, the parameter derived from the biological property is

, while the physicochemical property is the in vitro dissolution profile.

The main roles of IVIVC are:

1. To use dissolution test as a surrogate for human studies.
2. To supports and/or validate the use of
   dissolution
   methods and specifications.
3. To assist in quality control during manufacturing and selecting appropriate formulations

Example of a correlation model

${\displaystyle \operatorname {Fabs} =\operatorname {AbsScale} \times \operatorname {Diss} \times (\operatorname {t_{scale}} \times \operatorname {t_{vivo}} -\operatorname {t_{shift}} )-\operatorname {AbsBase} ,}$

where

• 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.

References

Sources

• 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