2. FDA
• A predictive mathematical model describing the
relationship between an in vitro property of
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
USP
• Establishment of a relationship between a
biological property produced from a dosage form
and a physiochemical property of the same
dosage form
2
3. To ensure batch to batch consistency in the physiological
performance of a drug product by use of such in vitro
values
To serve as a tool in the development of a new dosage
form with desired in vivo performance
To assist in validating or setting dissolution specifications
i.e. the dissolutions specifications are based on the
performance of product in vivo IV
It minimizes the number of bioequivalence studies
performed during the initial approval process and during
scaling up and post approval changes
Biowaiver for minor formulation and process
changes
3
4. Limited to certain drug product, it can
be used only on that particular
formulation
Drug product with different release
mechanisms
4
5. In vitro dissolution
parameters
In vivo plasma data
parameters
Time for specific amount of drug
to dissolve (50% of the dose)
AUC, Cmax
Amount dissolved at a specific
time point
Fraction absorbed, absorption
rate constant (ka)
Mean dissolution time Mean residence time, mean
dissolution time, mean
absorption time
Parameter estimated after
modelling the dissolution process
Conc.at time t
Brahmankar D M.Biopharmaceutics and Pharmacokinetics-A treatise.3rd ed.Delhi:Vallabh
prakashan;2015.335p. 5
6. • Parameters such as
amount of drug excreted
unchanged in the urine,
cumulative amount of
drug excreted as a
function of time.
Urinary
excretion
data
• An acute pharmacological
effect such as LD50 in
animals in related to any
of the dissolution
parameters
Pharmacolo
gical
response
6
7. Level A
Level B
Level C
Multiple Level C
Level D
Based on the ability
of the correlation to
reflect the complete
plasma level profile,
which will result
from administration
of the given dosage
form
7
8. It shows relationship between
fraction absorbed and fraction
dissolved.
No direct comparison is possible
It is considered as a predictive
model for relationship between the
entire In vitro and In vivo response
There exists a linear correlation 1:1.
There is point to pointrelationship.It
is highest level of correlation and
most preferred to achieve.
8
9. mean in vitro
dissolution
time is
compared
with mean
invivo
residence
time/mean in
vivo
dissolution
time
It is based on
statistical
moment
analysis
It is least used
for regulatory
purposes
It is not point
to point
correlation
9
10. It is a single point correlation between one dissolution
parameter like t 50% and one of the pharmacokinetic
parameter like
t max, AUC, C max
It is helpful in early stages of
formulation
10
11. It reflects the relationship between one or
several
pharmacokinetic parameters of interest and
amount
of drug dissolved at several time point of
dissolution.
It is similar to Level A correlation
M
U
L
T
I
p
L
E
L
E
V
E
L
C
CBrahmankar D M.Biopharmaceutics and Pharmacokinetics-A treatise.3rd
11
12. Bcs Classification system for Immediate release Drug product
and IVIVC Expectations
Class Solubility Permeability
IVIVC
Expectation for
immediate –
release product
Possibility of
predicting
IVIVC from
Dissolution
data
I. High High IVIVC expected YES
11. Low High IVIVC Expected Yes
111. High Low
Absorption is
rate limiting step NO
1V Low Low No IVIVC is
expected
No
12
Somnath sankore,Bhaswat chakraborty.Invitro-invitro correlation(ivivc):A
strategic tool in drug development.J Bioequiv availab.2003 jan;1-12
13
13. In biowaivers the
in vivo
bioavailability
and
bioequivalence
studies need not
to be conducted
for drug products
under following
circumstances:
13
1. Rapid and similar dissolution
2. High solubility
3. High permeability
4.Exicipient used in doseage form
5.Wide therapeutic window
