A review on "IN VITRO-IN VIVO CORRELATION"

1. IN VITRO-IN VIVO
CORRELATION
Prepared & Presented by:
K. Mondal

2. INTRODUCTION
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3. DEFINITION
1)United state pharmacopoeia definition :
The establishment of a rational relationship
between a biological property or a parameter derived
from a biological property produced by a dosage form
and a physiochemical property or characteristics dosage
form.
2) Food and drug administration definition:
IVIVC is a predictive mathematical model
describing the relationship between an invitro
properties of a dosage form and an in vivo response.

4. Advantages:
• Supports or validates the use of dissolution method
and specification.
• Serves as the surrogate of in vivo phenomena
• Assist quality control during manufacturing and
selecting appropriate formulation.
• To minimize the bioequivalence studies performed
during the initial approval process and during the
scaling up and post approval changes
• Reduce the requirment of animals & human for
bioavailability testing.

5. Limitations:
• It is limited to a certain drug product. It can be used
only that particular formulation.
• Cannot be used across the drug product with
different release pattern.
• It is unable to accurately estimate the rate of drug
absorption ,cmax, prediction, error will found to be
20%.

6. CORELATION LEVEL:
• 1)Level A correlation:- The height category of
correlation and represent a point to point
relationship between invitro dissolution rate
in vivo input rate of the drug from the dosage
form

7. LEVEL B CORELATION:-It utilizes the principles of
statistical mean invitro dissolution time(MVT,VITRO) of the
product is correlate to either mean in vivo residence
time(MRT) or to mean in vivo dissolution time(MVT,VIVO).

8. LEVEL C CORELATION:-Here the one dissolution time point
(t90%,t50%) is compared to one mean pharmacokinetic
parameter such as AUC, Cmax. It is a single point
correlation does not reflects the entire shape of plasma
drug concentration.

9. • Class1 drug :exhibit a high absorption no &
high dissolution no & rate limiting step is drug
dissolution or gastric empting time.
• Eg. metoprolol
IVIVC IS EXPECTED

10. • Class-2 drug:-drugs under this class have low solubility
and high permeability
• Eg-phenytoin
• Ivivc expected
• Class-3 drug:-drugs like permeability is rate controlling
step rapid dissolution is particularly desirable in order to
maximize the contact time between dissolve drug and
absorption mucosa.
• Eg. cimetidine
• Limited or no IvIvc expected
• Class 4 drug:- they have low solubility low permeability
and significant problem in oral dosage form.
• Limited or no IvIvc expected

11. Four basic type of dissolution apparatus is:
A)Rotating basket apparatus (apparatus 1): Tested are
conventional tablets, chewable tablets, controlled release
formulations.
B) Rotating Paddle apparatus (apparatus 2): Tested
are tablets, orally disintegrating tablets, capsules,
controlled release products, suspensions.
C) Reciprocating cylinder: It is particularly used for
controlled-release bead-type formulations.
D) Flow-Through cell apparatus: Tested are formulations
containing poorly soluble drugs, powders and granules,
microparticles.

12. • Medium specification:-
o A common dissolution medium is water, stimulated gastric
fluid(pH-1.2),intestinal fluid(pH-6.8-7.4)
o For poorly water soluble drug, use of surfactant in the
dissolution medium is recommended
o The normal test duration for immediate release is 15to60
minutes with a single time point. for class1drug

13. Conclusion:
• IVIVC includes a surrogate for in vivo
bioavailability and further more it can also
allow to setting and validating of more
meaningful dissolution method and
qualification and assist for certain scale up
and post approval changes.
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14. References:
• The United Stated Pharmacopeia. (23thed.). (1995). In
Vitro and In Vivo Evaluation of Dosage form <1088>. 1824-
1929.
• Leeson, L. J. (1995). In vitro/ In vivo correlations.
Drug Information Journal.29,903-915.
• Young, D., Devane, J. G., and Butler, J.(Eds.) (1997). In Vitro-
In Vivo Correlations.New York: Plenum Press.
• Review Article, Amitava Ghosh et al. / Journal of Pharmacy
Research 2009, 2(8),1255-1260
• Page: 332-336, Biopharmaceutics and pharmacokinetics a
Treatise, D. M. Brahmankar and Sunil B. Jaiswal
• Dressman JB, Amidon GL, Reppas C, Shah VP. Dissolution
testing as a prognostic tool for oral drug absorption:
immediate release dosage forms. Pharm Res.
1999;15(1):11-22.
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15. THANK YOU
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