SlideShare une entreprise Scribd logo
1  sur  21
Télécharger pour lire hors ligne
IN VITRO IN VIVO
CORRELATIONS
BY
T.Dilip Kumar
M.S.(pharm.) Pharmaceutics
CONTENTS
• Definitions
• Significance of ivivc
• Parameters for correlation
• Levels of correlation
• Development of correlation
• Case study
• Conclusions
• References
2
Definitions
• In vitro dissolution: It’s a process of release of drug from
dosage form as measured in an in vitro dissolution apparatus
• In vivo dissolution: process of dissolution of drug in the GI
tract.
• Correlation: relationship between in vitro dissolution rate and
in vivo absorption rate as used in bio-equivalence guidance
• IVIVC has been defined as “a predictive mathematical model
describing the relationship between an in-vitro property of a
dosage form and an in-vivo response”
3
Significance of ivivc
• The main objective of developing and evaluating an IVIVC is
to enable the dissolution test to serve as a surrogate. It reduces
the number of bio-equivalence required for approval as well as
during scale up and post approval changes (SUPAC).
• IVIVC shortens the drug development period, economizes the
resources and leads to improved product quality.
• A means of assuring the bioavailability of active ingredients
from a dosage form.
• Supports and or validates the use of dissolution methods and
specifications
• IVIVC assists in supporting biowaivers.
4
Parameters for correlations
SL. No. IN VITRO INVIVO
1. Dissolution rate Absorption rate (or
absorption time)
2. Percent drug dissolved Percent of drug absorbed
3. Percent drug dissolved Maximum plasma
concentration, Cmax
4. Percent drug dissolved Serum drug
concentration, Cp
5
Figure 1: In vitro-in vivo correlations-
Dissolution time Vs absorption time of
three sustained release products
If dissolution of drug is rate
limiting step, the faster the
dissolution rate, the faster is
the rate of appearance of drug
in the plasma. Therefore,
absorption time and
dissolution time may be
considered for correlation
Dissolution rate versus absorption rate
6
Percent of drug dissolved versus percent of drug
absorbed:
. Appropriate dissolution medium and a
slow stirring rate during dissolution
should be considered to mimic in vivo
dissolution.
. If the drug is absorbed completely after
dissolution, a linear correlation may be
obtained by comparing the percent drug
absorbed to the percent drug dissolved.
Figure 2: In vitro-in vivo correlations-
Percent of drug dissolved Vs percent of
drug absorbed of three sustained release
aspirin products
7
Percent of drug dissolved versus maximum plasma
concentration:
A poorly formulated drug may not
be completely dissolved and
released, resulting in lower plasma
drug concentration.
The percentage of drug released at
any time interval will be greater
for more bioavailable drug
product, the peak serum
concentration will be higher for the
drug that shows highest percent of
drug dissolved.
Figure 3: percent drug dissolved in 30 minutes Vs
Cmax of drug for nine products of phenytoin (100
mg).
8
Serum drug concentration versus percent of drug
dissolved
• In a study on aspirin absorption,
serum concentration of aspirin
was correlated to percent of drug
dissolved using an in vitro
dissolution method
• Dissolution of drug is rate
limiting step, and various
formulations with different
dissolution rates has difference in
serum concentration of aspirin
9
Figure 4:In vitro-In vivo correlations-serum drug
concentration Vs percent of drug dissolved of
aspirin
Levels of correlation
• Level A Correlation
• Level B Correlation
• Level C Correlation
• Multiple Level C Correlation
10
Level A correlation
It is estimated by two step method,
deconvolution followed by comparison
of fraction of drug absorbed to the
fraction of drug dissolved.
Defines a direct relationship between in
vivo data such that measurement of in
vitro dissolution rate alone is sufficient
to determine the biopharmaceutical rate
of the dosage form.
An in vitro dissolution curve can serve
as a surrogate for in vivo performance
Figure 5: Correlation between percent
theophylline dissolved in vitro and
percent theophylline absorbed after
administration of extended release
product
11
Level B correlation:
Level B correlation utilizes the
principles of statistical moment
analysis.
Mean in vitro dissolution time
(MDTvitro) of the product is compared
to mean in vivo residence time
(MRT).
MRT may be calculated as the ratio of
the area under the first moment curve
(AUMC) to the AUC, where AUMC
is the area under the curve observed
for the product of time and
concentration versus time.
Figure 6: Correlation of mean in vitro
dissolution time (MDT) and mean in vivo
absorption time (MAT)
12
Level C correlation
Level C correlation represents a single
point correlation.
One dissolution time point (t50%, t90%,
etc.) is compared to one mean
pharmacokinetic parameter such as
AUC, tmax or Cmax.
Weakest level of correlation as partial
relationship between absorption and
dissolution is established. Figure 7: Correlation between percent drug
dissolved in 45 minutes and AUC of plasma
drug-time curve .
13
Multiple level C correlations
• Multiple Level C correlation relates one or several
pharmacokinetic parameters of interest (Cmax, AUC, or any
other suitable parameters) to the amount of drug dissolved at
several time points of the dissolution profile.
• Its correlation is more meaningful than that of Level C as
several time points are considered.
14
Development of in vivo/ in vitro
correlation
15
Case Studies
• In Vitro-in Vivo Correlation (IVIVC) Study Of
Leflunomide Loaded Microspheres.
• The parameters correlated were amount of drug dissolved to
the respective fraction of dose absorbed.
• The in vitro release from leflunomide microspheres
B1,B2,B3,B4 show good sustained release property
• The selected formulations were examined in In vivo rabbit
model, the Tmax of all microspheres were increased from 1 to
4hr confirming its sustaining property
• Degree A level of correlation was established from the results
16
17
CONCLUSIONS
• The current IVIVC studies have focused more on the
development and validation of level A IVIVC which gives
more useful information on the relationship between in vitro
release and in vivo absorption from dosage form.
• Levels B and C IVIVCs have been evaluated for several
purposes in formulation development, for example, to select
the appropriate excipients and optimize the manufacturing
processes.
• Present regulatory guidelines for IVIVC is only applicable to
oral conventional and modified release dosage forms;
however, further research is necessary to develop IVIVCs for
non-oral products, inhaled medicines and dermatological
medicaments also.
18
References
• Leon Shargel, Susanna wu-pong, Andrew Yu. Applied
biopharmaceutics and pharmacokinetics. 6th edition, pg no- 380-
383.
• Sundaramoorthi Nainar, Kingston Rajiah, Santhosam Angamuthu,
D Prabakaran and Ravisekhar Kasibhatta. Biopharmaceutical
Classification System in In-vitro/In-vivo Correlation: Concept
and Development Strategies in Drug Delivery. Tropical Journal of
Pharmaceutical Research April 2012; 11 (2): 319-329
• Rabindranath pal, Manas Chakraborty, Rabindra Debnath and
Bijan K Gupta. In vitro-In vivo Correlation (IVIVC) study of
Leflunomide loaded microspheres. International Journal of
Pharmacy and Pharmaceutical Sciences, Vol. 1, Suppl 1, Nov.-
Dec. 2009
19
References
• Hitesh Jain , Kruti Joshi1, Shweta Gediya, Vishal Sutariya,
Hirak Shah, T. Y. Pasha. IN VITRO IN VIVO CORRELATION
(IVIVC): A REVIEW. Imperial Journal of Pharmaceutics &
Cosmetology.
20
21

Contenu connexe

Tendances

Methods For Assesment Of Bioavailability
Methods For Assesment Of Bioavailability Methods For Assesment Of Bioavailability
Methods For Assesment Of Bioavailability Anindya Jana
 
bioequivalence study design
bioequivalence study designbioequivalence study design
bioequivalence study designJuhi Priya
 
Four Levels of In-Vitro-In-Vivo Correlation
Four Levels of In-Vitro-In-Vivo CorrelationFour Levels of In-Vitro-In-Vivo Correlation
Four Levels of In-Vitro-In-Vivo CorrelationBhaswat Chakraborty
 
P h partition hypothesis
P h partition hypothesisP h partition hypothesis
P h partition hypothesisZahid1392
 
Properties of GI tract, pH partition hypothesis
Properties of GI tract, pH partition hypothesis Properties of GI tract, pH partition hypothesis
Properties of GI tract, pH partition hypothesis Naveen Reddy
 
Causes of Non linear pharmacokinetics
Causes of Non linear pharmacokineticsCauses of Non linear pharmacokinetics
Causes of Non linear pharmacokineticsSnehal Patel
 
Bioequivalence 112070804009
Bioequivalence  112070804009Bioequivalence  112070804009
Bioequivalence 112070804009Patel Parth
 
Bioequivalence studies
Bioequivalence studiesBioequivalence studies
Bioequivalence studiesSujit Patel
 
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...Manikant Prasad Shah
 
Non linear Pharmacokinetics
Non linear PharmacokineticsNon linear Pharmacokinetics
Non linear PharmacokineticsAreej Abu Hanieh
 
WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)
WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)
WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)DR. METI.BHARATH KUMAR
 
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
 
Rate limiting steps in drug absorption [autosaved]
Rate limiting steps in drug absorption [autosaved]Rate limiting steps in drug absorption [autosaved]
Rate limiting steps in drug absorption [autosaved]Nagaraju Ravouru
 
microspheres types , preparation and evaluation
microspheres types , preparation and evaluationmicrospheres types , preparation and evaluation
microspheres types , preparation and evaluationSowjanya
 
In vitro Dissolution Testing Models
In vitro Dissolution Testing ModelsIn vitro Dissolution Testing Models
In vitro Dissolution Testing ModelsAmeer Ahmed
 

Tendances (20)

Methods For Assesment Of Bioavailability
Methods For Assesment Of Bioavailability Methods For Assesment Of Bioavailability
Methods For Assesment Of Bioavailability
 
bioequivalence study design
bioequivalence study designbioequivalence study design
bioequivalence study design
 
Non linear pharmacokinetics
Non linear pharmacokineticsNon linear pharmacokinetics
Non linear pharmacokinetics
 
Four Levels of In-Vitro-In-Vivo Correlation
Four Levels of In-Vitro-In-Vivo CorrelationFour Levels of In-Vitro-In-Vivo Correlation
Four Levels of In-Vitro-In-Vivo Correlation
 
P h partition hypothesis
P h partition hypothesisP h partition hypothesis
P h partition hypothesis
 
Properties of GI tract, pH partition hypothesis
Properties of GI tract, pH partition hypothesis Properties of GI tract, pH partition hypothesis
Properties of GI tract, pH partition hypothesis
 
Pharmacokinetic models
Pharmacokinetic modelsPharmacokinetic models
Pharmacokinetic models
 
Causes of Non linear pharmacokinetics
Causes of Non linear pharmacokineticsCauses of Non linear pharmacokinetics
Causes of Non linear pharmacokinetics
 
Bioequivalence 112070804009
Bioequivalence  112070804009Bioequivalence  112070804009
Bioequivalence 112070804009
 
Bioequivalence studies
Bioequivalence studiesBioequivalence studies
Bioequivalence studies
 
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...
Bioavailability , absolute bioavalability, relative bioavailability, Purpose ...
 
Non linear Pharmacokinetics
Non linear PharmacokineticsNon linear Pharmacokinetics
Non linear Pharmacokinetics
 
WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)
WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)
WAGNER NELSON METHOD (Contact me: dr.m.bharathkumar@gmail.com)
 
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...
 
Rate limiting steps in drug absorption [autosaved]
Rate limiting steps in drug absorption [autosaved]Rate limiting steps in drug absorption [autosaved]
Rate limiting steps in drug absorption [autosaved]
 
Non compartment model
Non compartment modelNon compartment model
Non compartment model
 
Pharmacokinetic models
Pharmacokinetic  modelsPharmacokinetic  models
Pharmacokinetic models
 
microspheres types , preparation and evaluation
microspheres types , preparation and evaluationmicrospheres types , preparation and evaluation
microspheres types , preparation and evaluation
 
In vitro Dissolution Testing Models
In vitro Dissolution Testing ModelsIn vitro Dissolution Testing Models
In vitro Dissolution Testing Models
 
Multicompartment Models
Multicompartment ModelsMulticompartment Models
Multicompartment Models
 

Similaire à In-Vivo In-Vitro Correlation

Iviv corelation
Iviv corelationIviv corelation
Iviv corelationZahid1392
 
Iv dissolution iviv corelation
Iv dissolution iviv corelationIv dissolution iviv corelation
Iv dissolution iviv corelationZahid1392
 
IVIVC detail topic explanation biopharmaceutics.pdf
IVIVC detail topic explanation biopharmaceutics.pdfIVIVC detail topic explanation biopharmaceutics.pdf
IVIVC detail topic explanation biopharmaceutics.pdfUVAS
 
In vivo in vitro correlation - copy
In vivo in vitro correlation - copyIn vivo in vitro correlation - copy
In vivo in vitro correlation - copyBHUPINDER KAUR
 
BIO AVAILABILITY & Bio equivalence.pptx
BIO AVAILABILITY & Bio equivalence.pptxBIO AVAILABILITY & Bio equivalence.pptx
BIO AVAILABILITY & Bio equivalence.pptxMANSISONI146297
 
Bioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptxBioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptxabhisheksinghcompute
 
Bioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptxBioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptxabhisheksinghcompute
 
Bioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptxBioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptxabhisheksinghcompute
 
In vitro in vivo correlation
In vitro  in vivo correlationIn vitro  in vivo correlation
In vitro in vivo correlationAswathi S Nair
 
Invitro invivo correlation
Invitro invivo correlationInvitro invivo correlation
Invitro invivo correlationkvineetha8
 
Bioavailability and bioequivalance studies
Bioavailability and bioequivalance studies Bioavailability and bioequivalance studies
Bioavailability and bioequivalance studies ROHIT
 
ivivc correlation
ivivc correlationivivc correlation
ivivc correlationHARISH C
 
IN-VITRO AND IN-VIVO CORRELATIONS.pptx
IN-VITRO AND IN-VIVO CORRELATIONS.pptxIN-VITRO AND IN-VIVO CORRELATIONS.pptx
IN-VITRO AND IN-VIVO CORRELATIONS.pptxShamsElfalah
 
Dissolution method and ivivc by ranjeet singh
Dissolution method and ivivc by ranjeet singhDissolution method and ivivc by ranjeet singh
Dissolution method and ivivc by ranjeet singhRanjeet Singh
 
IN VITRO-IN VIVO CORRELATION.
IN VITRO-IN VIVO CORRELATION. IN VITRO-IN VIVO CORRELATION.
IN VITRO-IN VIVO CORRELATION. K Mondal
 
In vitro In vivo correlation.pptx
In vitro In vivo correlation.pptxIn vitro In vivo correlation.pptx
In vitro In vivo correlation.pptxSimonGermany1
 

Similaire à In-Vivo In-Vitro Correlation (20)

Iviv corelation
Iviv corelationIviv corelation
Iviv corelation
 
Iv dissolution iviv corelation
Iv dissolution iviv corelationIv dissolution iviv corelation
Iv dissolution iviv corelation
 
IVIVC detail topic explanation biopharmaceutics.pdf
IVIVC detail topic explanation biopharmaceutics.pdfIVIVC detail topic explanation biopharmaceutics.pdf
IVIVC detail topic explanation biopharmaceutics.pdf
 
In vivo in vitro correlation - copy
In vivo in vitro correlation - copyIn vivo in vitro correlation - copy
In vivo in vitro correlation - copy
 
IN VITRO IN VIVO CORRELATION
IN VITRO IN VIVO CORRELATION IN VITRO IN VIVO CORRELATION
IN VITRO IN VIVO CORRELATION
 
Madhu k s
Madhu k s Madhu k s
Madhu k s
 
BIO AVAILABILITY & Bio equivalence.pptx
BIO AVAILABILITY & Bio equivalence.pptxBIO AVAILABILITY & Bio equivalence.pptx
BIO AVAILABILITY & Bio equivalence.pptx
 
Bioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptxBioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptx
 
Bioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptxBioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptx
 
Bioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptxBioavailability and bioequivalence of Drug Productppt2.pptx
Bioavailability and bioequivalence of Drug Productppt2.pptx
 
IVIVC-
IVIVC-IVIVC-
IVIVC-
 
In vitro in vivo correlation
In vitro  in vivo correlationIn vitro  in vivo correlation
In vitro in vivo correlation
 
Invitro invivo correlation
Invitro invivo correlationInvitro invivo correlation
Invitro invivo correlation
 
Bioavailability and bioequivalance studies
Bioavailability and bioequivalance studies Bioavailability and bioequivalance studies
Bioavailability and bioequivalance studies
 
ivivc correlation
ivivc correlationivivc correlation
ivivc correlation
 
IN-VITRO AND IN-VIVO CORRELATIONS.pptx
IN-VITRO AND IN-VIVO CORRELATIONS.pptxIN-VITRO AND IN-VIVO CORRELATIONS.pptx
IN-VITRO AND IN-VIVO CORRELATIONS.pptx
 
Dissolution method and ivivc by ranjeet singh
Dissolution method and ivivc by ranjeet singhDissolution method and ivivc by ranjeet singh
Dissolution method and ivivc by ranjeet singh
 
IN VITRO-IN VIVO CORRELATION.
IN VITRO-IN VIVO CORRELATION. IN VITRO-IN VIVO CORRELATION.
IN VITRO-IN VIVO CORRELATION.
 
Bio availability and bio equivalence
Bio availability and bio equivalenceBio availability and bio equivalence
Bio availability and bio equivalence
 
In vitro In vivo correlation.pptx
In vitro In vivo correlation.pptxIn vitro In vivo correlation.pptx
In vitro In vivo correlation.pptx
 

Dernier

Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeTracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeQuick MedTalk
 
Neutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractionsNeutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractionsPradnya Wadekar
 
TARGET DELINEATION IN VULVAL CANCER BY DR KANHU
TARGET DELINEATION IN VULVAL CANCER BY DR KANHUTARGET DELINEATION IN VULVAL CANCER BY DR KANHU
TARGET DELINEATION IN VULVAL CANCER BY DR KANHUKanhu Charan
 
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptxNECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptxSizan Thapa
 
CELL BLOCK PREPARATION AND ITS IMPORTANCE
CELL BLOCK PREPARATION AND ITS IMPORTANCECELL BLOCK PREPARATION AND ITS IMPORTANCE
CELL BLOCK PREPARATION AND ITS IMPORTANCEShubhadip Ghosh
 
Substance use disorder (drug addict ), Addiction
Substance use disorder (drug addict ), AddictionSubstance use disorder (drug addict ), Addiction
Substance use disorder (drug addict ), AddictionZeinabEmad3
 
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdf
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdfSGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdf
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdfHongBiThi1
 
Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)Ahmad Thanin
 
Ovarian tumors Lecture notes for MBBS.pptx
Ovarian tumors Lecture notes for MBBS.pptxOvarian tumors Lecture notes for MBBS.pptx
Ovarian tumors Lecture notes for MBBS.pptxSizan Thapa
 
Brief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptxBrief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptxTina Purnat
 
Reproductive and Child Health Services ppt.pptx
Reproductive and Child Health Services ppt.pptxReproductive and Child Health Services ppt.pptx
Reproductive and Child Health Services ppt.pptxVeereshDemashetti
 
Ten lessons learnt as anesthetist.pptx
Ten  lessons  learnt as anesthetist.pptxTen  lessons  learnt as anesthetist.pptx
Ten lessons learnt as anesthetist.pptxtusharchokshi1
 
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALK
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALKLaryngeal papillomatosis .pdf ENT BY QUICKMEDTALK
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALKQuick MedTalk
 
Routine Medicine Laboratory Testing _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...
Routine Medicine Laboratory Testing  _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...Routine Medicine Laboratory Testing  _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...
Routine Medicine Laboratory Testing _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...DUY NGUYEN PHUC
 
SMA Implementation science seminar (Day 1).pptx
SMA Implementation science seminar (Day 1).pptxSMA Implementation science seminar (Day 1).pptx
SMA Implementation science seminar (Day 1).pptxAbdirahmanWaseem
 
Thyroid function tests for MBBS, LAB. MED & BDS.pptx
Thyroid function tests for MBBS, LAB. MED & BDS.pptxThyroid function tests for MBBS, LAB. MED & BDS.pptx
Thyroid function tests for MBBS, LAB. MED & BDS.pptxRajendra Dev Bhatt
 
TARGET DELINEATION IN RECTUM CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM  CANCER BY DR KANHUTARGET DELINEATION IN RECTUM  CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM CANCER BY DR KANHUKanhu Charan
 
ANATOMY OF THE CEREBRUM WITH CLINICAL ANATOMY.pptx
ANATOMY OF THE CEREBRUM WITH CLINICAL ANATOMY.pptxANATOMY OF THE CEREBRUM WITH CLINICAL ANATOMY.pptx
ANATOMY OF THE CEREBRUM WITH CLINICAL ANATOMY.pptxsiddharthroy26587
 

Dernier (20)

Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeTracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
 
Neutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractionsNeutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractions
 
TARGET DELINEATION IN VULVAL CANCER BY DR KANHU
TARGET DELINEATION IN VULVAL CANCER BY DR KANHUTARGET DELINEATION IN VULVAL CANCER BY DR KANHU
TARGET DELINEATION IN VULVAL CANCER BY DR KANHU
 
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptxNECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
 
CELL BLOCK PREPARATION AND ITS IMPORTANCE
CELL BLOCK PREPARATION AND ITS IMPORTANCECELL BLOCK PREPARATION AND ITS IMPORTANCE
CELL BLOCK PREPARATION AND ITS IMPORTANCE
 
Substance use disorder (drug addict ), Addiction
Substance use disorder (drug addict ), AddictionSubstance use disorder (drug addict ), Addiction
Substance use disorder (drug addict ), Addiction
 
Catalysts for Change in SCLC: Optimizing the Use of Standard Therapies and Ac...
Catalysts for Change in SCLC: Optimizing the Use of Standard Therapies and Ac...Catalysts for Change in SCLC: Optimizing the Use of Standard Therapies and Ac...
Catalysts for Change in SCLC: Optimizing the Use of Standard Therapies and Ac...
 
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdf
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdfSGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdf
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdf
 
Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)
 
Ovarian tumors Lecture notes for MBBS.pptx
Ovarian tumors Lecture notes for MBBS.pptxOvarian tumors Lecture notes for MBBS.pptx
Ovarian tumors Lecture notes for MBBS.pptx
 
Oral disorders .pptx
Oral disorders .pptxOral disorders .pptx
Oral disorders .pptx
 
Brief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptxBrief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptx
 
Reproductive and Child Health Services ppt.pptx
Reproductive and Child Health Services ppt.pptxReproductive and Child Health Services ppt.pptx
Reproductive and Child Health Services ppt.pptx
 
Ten lessons learnt as anesthetist.pptx
Ten  lessons  learnt as anesthetist.pptxTen  lessons  learnt as anesthetist.pptx
Ten lessons learnt as anesthetist.pptx
 
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALK
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALKLaryngeal papillomatosis .pdf ENT BY QUICKMEDTALK
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALK
 
Routine Medicine Laboratory Testing _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...
Routine Medicine Laboratory Testing  _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...Routine Medicine Laboratory Testing  _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...
Routine Medicine Laboratory Testing _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...
 
SMA Implementation science seminar (Day 1).pptx
SMA Implementation science seminar (Day 1).pptxSMA Implementation science seminar (Day 1).pptx
SMA Implementation science seminar (Day 1).pptx
 
Thyroid function tests for MBBS, LAB. MED & BDS.pptx
Thyroid function tests for MBBS, LAB. MED & BDS.pptxThyroid function tests for MBBS, LAB. MED & BDS.pptx
Thyroid function tests for MBBS, LAB. MED & BDS.pptx
 
TARGET DELINEATION IN RECTUM CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM  CANCER BY DR KANHUTARGET DELINEATION IN RECTUM  CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM CANCER BY DR KANHU
 
ANATOMY OF THE CEREBRUM WITH CLINICAL ANATOMY.pptx
ANATOMY OF THE CEREBRUM WITH CLINICAL ANATOMY.pptxANATOMY OF THE CEREBRUM WITH CLINICAL ANATOMY.pptx
ANATOMY OF THE CEREBRUM WITH CLINICAL ANATOMY.pptx
 

In-Vivo In-Vitro Correlation

  • 1. IN VITRO IN VIVO CORRELATIONS BY T.Dilip Kumar M.S.(pharm.) Pharmaceutics
  • 2. CONTENTS • Definitions • Significance of ivivc • Parameters for correlation • Levels of correlation • Development of correlation • Case study • Conclusions • References 2
  • 3. Definitions • In vitro dissolution: It’s a process of release of drug from dosage form as measured in an in vitro dissolution apparatus • In vivo dissolution: process of dissolution of drug in the GI tract. • Correlation: relationship between in vitro dissolution rate and in vivo absorption rate as used in bio-equivalence guidance • IVIVC has been defined as “a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response” 3
  • 4. Significance of ivivc • The main objective of developing and evaluating an IVIVC is to enable the dissolution test to serve as a surrogate. It reduces the number of bio-equivalence required for approval as well as during scale up and post approval changes (SUPAC). • IVIVC shortens the drug development period, economizes the resources and leads to improved product quality. • A means of assuring the bioavailability of active ingredients from a dosage form. • Supports and or validates the use of dissolution methods and specifications • IVIVC assists in supporting biowaivers. 4
  • 5. Parameters for correlations SL. No. IN VITRO INVIVO 1. Dissolution rate Absorption rate (or absorption time) 2. Percent drug dissolved Percent of drug absorbed 3. Percent drug dissolved Maximum plasma concentration, Cmax 4. Percent drug dissolved Serum drug concentration, Cp 5
  • 6. Figure 1: In vitro-in vivo correlations- Dissolution time Vs absorption time of three sustained release products If dissolution of drug is rate limiting step, the faster the dissolution rate, the faster is the rate of appearance of drug in the plasma. Therefore, absorption time and dissolution time may be considered for correlation Dissolution rate versus absorption rate 6
  • 7. Percent of drug dissolved versus percent of drug absorbed: . Appropriate dissolution medium and a slow stirring rate during dissolution should be considered to mimic in vivo dissolution. . If the drug is absorbed completely after dissolution, a linear correlation may be obtained by comparing the percent drug absorbed to the percent drug dissolved. Figure 2: In vitro-in vivo correlations- Percent of drug dissolved Vs percent of drug absorbed of three sustained release aspirin products 7
  • 8. Percent of drug dissolved versus maximum plasma concentration: A poorly formulated drug may not be completely dissolved and released, resulting in lower plasma drug concentration. The percentage of drug released at any time interval will be greater for more bioavailable drug product, the peak serum concentration will be higher for the drug that shows highest percent of drug dissolved. Figure 3: percent drug dissolved in 30 minutes Vs Cmax of drug for nine products of phenytoin (100 mg). 8
  • 9. Serum drug concentration versus percent of drug dissolved • In a study on aspirin absorption, serum concentration of aspirin was correlated to percent of drug dissolved using an in vitro dissolution method • Dissolution of drug is rate limiting step, and various formulations with different dissolution rates has difference in serum concentration of aspirin 9 Figure 4:In vitro-In vivo correlations-serum drug concentration Vs percent of drug dissolved of aspirin
  • 10. Levels of correlation • Level A Correlation • Level B Correlation • Level C Correlation • Multiple Level C Correlation 10
  • 11. Level A correlation It is estimated by two step method, deconvolution followed by comparison of fraction of drug absorbed to the fraction of drug dissolved. Defines a direct relationship between in vivo data such that measurement of in vitro dissolution rate alone is sufficient to determine the biopharmaceutical rate of the dosage form. An in vitro dissolution curve can serve as a surrogate for in vivo performance Figure 5: Correlation between percent theophylline dissolved in vitro and percent theophylline absorbed after administration of extended release product 11
  • 12. Level B correlation: Level B correlation utilizes the principles of statistical moment analysis. Mean in vitro dissolution time (MDTvitro) of the product is compared to mean in vivo residence time (MRT). MRT may be calculated as the ratio of the area under the first moment curve (AUMC) to the AUC, where AUMC is the area under the curve observed for the product of time and concentration versus time. Figure 6: Correlation of mean in vitro dissolution time (MDT) and mean in vivo absorption time (MAT) 12
  • 13. Level C correlation Level C correlation represents a single point correlation. One dissolution time point (t50%, t90%, etc.) is compared to one mean pharmacokinetic parameter such as AUC, tmax or Cmax. Weakest level of correlation as partial relationship between absorption and dissolution is established. Figure 7: Correlation between percent drug dissolved in 45 minutes and AUC of plasma drug-time curve . 13
  • 14. Multiple level C correlations • Multiple Level C correlation relates one or several pharmacokinetic parameters of interest (Cmax, AUC, or any other suitable parameters) to the amount of drug dissolved at several time points of the dissolution profile. • Its correlation is more meaningful than that of Level C as several time points are considered. 14
  • 15. Development of in vivo/ in vitro correlation 15
  • 16. Case Studies • In Vitro-in Vivo Correlation (IVIVC) Study Of Leflunomide Loaded Microspheres. • The parameters correlated were amount of drug dissolved to the respective fraction of dose absorbed. • The in vitro release from leflunomide microspheres B1,B2,B3,B4 show good sustained release property • The selected formulations were examined in In vivo rabbit model, the Tmax of all microspheres were increased from 1 to 4hr confirming its sustaining property • Degree A level of correlation was established from the results 16
  • 17. 17
  • 18. CONCLUSIONS • The current IVIVC studies have focused more on the development and validation of level A IVIVC which gives more useful information on the relationship between in vitro release and in vivo absorption from dosage form. • Levels B and C IVIVCs have been evaluated for several purposes in formulation development, for example, to select the appropriate excipients and optimize the manufacturing processes. • Present regulatory guidelines for IVIVC is only applicable to oral conventional and modified release dosage forms; however, further research is necessary to develop IVIVCs for non-oral products, inhaled medicines and dermatological medicaments also. 18
  • 19. References • Leon Shargel, Susanna wu-pong, Andrew Yu. Applied biopharmaceutics and pharmacokinetics. 6th edition, pg no- 380- 383. • Sundaramoorthi Nainar, Kingston Rajiah, Santhosam Angamuthu, D Prabakaran and Ravisekhar Kasibhatta. Biopharmaceutical Classification System in In-vitro/In-vivo Correlation: Concept and Development Strategies in Drug Delivery. Tropical Journal of Pharmaceutical Research April 2012; 11 (2): 319-329 • Rabindranath pal, Manas Chakraborty, Rabindra Debnath and Bijan K Gupta. In vitro-In vivo Correlation (IVIVC) study of Leflunomide loaded microspheres. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 1, Suppl 1, Nov.- Dec. 2009 19
  • 20. References • Hitesh Jain , Kruti Joshi1, Shweta Gediya, Vishal Sutariya, Hirak Shah, T. Y. Pasha. IN VITRO IN VIVO CORRELATION (IVIVC): A REVIEW. Imperial Journal of Pharmaceutics & Cosmetology. 20
  • 21. 21