This document discusses the correlation of in vivo drug data with in vitro dissolution data. It begins by defining in vitro-in vivo correlation (IVIVC) as a predictive mathematical model relating an in vitro property like dissolution rate to an in vivo response like plasma drug concentration. The objectives of IVIVC include reducing human testing and regulatory burdens. There are different levels of IVIVC - Level A provides the closest correlation while Level D is only qualitative. Level A correlates dissolution directly to absorption rate while Level C relates a parameter like AUC to a dissolution parameter. IVIVC can be used to justify formulation and process changes without additional human studies.

1. CORRELATION OF IN-VIVO DATA
WITH IN-VITRO DISSOLUTION DATA
PRESENTED BY
NAVYASHREE G
II SEM M PHARMACY
DEPT PHARMACEUTICS
PRESENTED TO
PROF H S KEERTHY
DEPT OF PHARMACEUTICS
MALLIGE COLLEGE OF PHARMACY
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2. CONTENTS
 Introduction
 Objectives
 Levels of correlation
 Application of IVIVC
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3. INTRODUCTION
 In vitro - In vivo correlation is defined as the
predictive mathematical model that describes the
relationship between an in-vitro property(such as
the rate of dissolution) of a dosage form and an in-
vivo response( such as the plasma drug
concentration).
 In vitro property is the rate or extent of drug
dissolution or release while , in-vivo response is the
plasma drug concentration or amount of drug
absorbed.
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4.  OBJECTIVES
1. Setting up of an in-vitro release test that would
serve as a surrogate for in- vivo plasma profiles
(bio equivalence testing)
2. To minimize unnecessary human testing.
3. Decreased regulatory burdens.
4. To set up bio pharmaceutically meaningful in-vitro
release specifications.
5. Minimization of cost and time required in
additional bioavailability studies.
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5.  LEVELS OF CORRELATION
 Four levels of correlation can be found in FDA
guidelines.
 Each level denotes its ability to predict invivo
response of dosage form from its in vitro property.
 The higher the level better is the correlation.
1) Level A correlation
2) Level B correlation
3) Level C correlation
4) Multiple level C correlation
5) Level D correlation
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6. LEVEL A CORRELATION
 It represents the relationship between in vitro
dissolution and in vivo input rate.
 For developing a correlation between two
parameters one variable should be common
between them. 6/18

7.  Here the data available is in vitro dissolution profile
and in vivo plasma drug concentration profile.
 A correlation of this type is generally linear and
represents a point to point relationship between in-
vitro dissolution and in-vivo input rate.
 Advantages of level A correlation
 A point to point correlation is developed. The invitro
dissolition curve serves as a surrogate for invivo
performance. Any change in manufacturing procedure
or modification in the formula can be justified without
the need for additional human studies.
 The invivo dissolution serves as an invivo indicating
quality control procedure for predicting dosage form’s
performance.
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8. LEVEL B CORRELATION
 It uses the principles of statistical movement analysis.
 The mean in-vitro dissolution time is compared either to the
mean residence time or the to the mean in-vivo dissolution
time.
 It doesn’t uniquely reflect the actual in-vivo plasma level
curve, because a number of different in-vivo curves will
produce similar mean residence time values.
 It is the least useful correlation for regulatory purposes. 8/18

9.  A Level C IVIVC establishes a single point relationship between a
dissolution parameter, for example,t50% 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 ER products .
 It is helpful in early stages of formulation development when pilot
formulations are being selected. 9/18
LEVEL C CORRELATION

10.  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.
 For the establishment of a correlation as described
in the FDA guidance, various parameters can be
used as presented in following table.
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11. 11/18

12. 12/18

13. MULTIPLE LEVEL C CORRELATION
 It reflects the relationship between one or several
pharmacokinetic parameters of interest and amount
of drug dissolved at various time points of
dissolution profile.
 It should be based on at least 3 dissolution time
points that include an arly, middle and last stage of
dissolution.
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14. LEVEL D CORRELATION
 It is a rank order and qualitative analysis and is not
considered useful for regulatory purposes.
 It is not a formal correlation but serves as an aid in
the development of a formulation or processing
procedue.
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15. APPLICATIONS OF IVIVC
 To use in in-vitro dissolution study as a surrogate for
human BE studies. This will reduce the number of
human BE studies during the initial approval process
as well as scale up and post approval changes.
 Justification for therapeutic product quality.
 Enhanced significance of invitro testing.
 During scale up, the dissolution data to judge the
impact of process changes as well establishing final
specifications for dissolution.
 The database may be utilized during further scale up
and site transfer as well as supporting post approval
changes.
 It ensure batch to batch consistency in the
physiological performance of a drug product.
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16. UNIVERSITY QUESTIONS
 Discuss briefly in-vitro, in-vivo correlation of drug
dissolution. ( june 2023)
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17. REFERENCES
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• A Text book of ADVANCED BIOPHARMACEUTICS AND
PHARMACOKINETICS BY PV PUBLICATIONS
• SLIDESHARE NOTES

18. THANK
YOU
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