In-vitro and In-vivo- Correlation study (IVOVC)

Dr. Anuj Malik
Professor
MM College of Pharmacy,
MM (Deemed to be University), Mullana,
Ambala (HARYANA)
In-vitro and In-vivo
Correlations

COURSE OUTCOME
1. To understand the principle underlying techniques of
Biopharmaceutics and pharmacokinetics in drug delivery at the
pre-clinical stage
2. To know how to determine the physicochemical properties of
drug and drug concentration of pharmaceutical dosage form
3. To know how pharmacokinetic parameter results are analyzed
4. To utilize such knowledge in designing of formulations to address
potential pharmacokinetics issues of drug

Learning Outcomes
After completion of this this chapter the students
will be able -
⚫ To understand the concept In-vitro and In-vivo
Correlations.
⚫ To understand the mechanism of In-vitro and In-vivo
Correlations.
⚫ To understand the principal underlying and clinical
application of In-vitro and In-vivo Correlations

Introduction
Correlations between in vitro and in vivo data (IVIVC) are often used during
pharmaceutical development
⚫ in order to reduce development time and optimize the formulation.
⚫ A good correlation is a tool for predicting in vivo results based on in vitro
data.
⚫ IVIVC allows dosage form optimization with the fewest possible trials in
man, fixes dissolution acceptance
⚫ The FDA defines IVIVC as “a predictive mathematical model describing
the relationship between an in vitro property of an extended release
dosage form (usually the rate or extent of drug dissolution or release)
and a relevant in vivo response, e.g., plasma drug concentration or
amount of drug absorbed.”

Level A-IVIVC
A correlation of this type is generally linear and represents a point-to-point
relationship between in vitro dissolution and the in vivo input rate (e.g., the in vivo
dissolution of the drug from the dosage form). In a linear correlation, the in vitro
dissolution and in vivo input curves may be directly superimposable or may be
made to be superimposable by the use of a scaling factor. Nonlinear correlations,
while uncommon, may also be appropriate. Alternative approaches to developing a
Level A IVIVC are possible. Whatever the method used to establish a Level A IVIVC,
the model should predict the entire in vivo time course from the in vitro data. In
this context, the model refers to the relationship between in vitro dissolution of an
dosage form and an in vivo response such as plasma drug concentration or amount of
drug absorbed.

Level B-IVIVC
A Level B IVIVC uses the principles of statistical moment
analysis. The mean in vitro dissolution time is compared
either to the mean residence time or to the mean in vivo
dissolution time. A Level B correlation does not uniquely
reflect the actual in vivo plasma level curve, because a
number of different in vivo curves will produce similar
mean residence time values.

Level C-IVIVC
A Level C IVIVC establishes a single point relationship between a dissolution
parameter for example,t50%,percent dissolved in 4 hours and a
pharmacokinetic parameter (e.g., AUC, Cmax, Tmax). A Level C correlation
does not reflect the complete shape of the plasma concentration-time curve,
which is the critical factor that defines the performance of products. In addition
to these three levels, a combination of various levels C is also described: A
multiple Level C correlation relates one or several pharmacokinetic parameters
of interest to the amount of drug dissolved at several time points of the
dissolution profile.

IVIVC-Significance
A Level A correlation defines a linear relationship between in vitro and
in vivo data so that measurement of the in vitro dissolution rate alone is
sufficient to determine the pharmacokinetic profile in vivo. After a
proper validation, IVIVC predicts the in vivo bioavailability results from
in vitro dissolution data, and this simulation reflects the in vivo behavior
of the various formulations.

Conclusion
Level A IVIVCs define the relationship between an in vitro dissolution curve and an
in vivo input (absorption) profile. A, Level A correlation should always be tried a
priori in order to have a tool that allows a complete in vivo prediction from an in vitro
dissolution curve and thus accelerates the development and assists in some
regulatory aspects (SUPAC, Scale-up and Post-Approval Changes). The correlation
quality depends solely on the quality of the data. As in vivo data are now well
standardized, the main effort must be directed to the in vitro data. Various
apparatus and media should be tested and assessed in terms of their in vivo
predictability. The user should always be aware of the limits of the method and of
the confidence of its prediction.

In-vitro and In-vivo- Correlation study (IVOVC)

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