Invitro invivo correlation

Invitro invivo correlation

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  Presented by, Pallab KumarPal M.Pharm, 1st year(Pharmaceutics) Roll no. 10 Under the guidance of, Dr. Somasree Ray Astt. Professor (Department of Pharmaceutics) Gupta College of Technological Sciences
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  Introduction In-vitro study meansstudy in an artificial environment outside the living organism In-vivo study means study in living system or living organism Invitro-invivo correlation is a predictive mathematical model describing relation between invtro dissolution parameters and corresponding invivo data and response (FDA definition)
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  Basic requirements fordeveloping IVIVC Data obtained from human studies are required for regulatory consideration of the correlation Two or more drug product formulations with different release rates are developed and their in vitro dissolution profiles generated using an appropriate dissolution method Usage of same dissolution method for all the formulations Plasma concentration data from a bioavailability study for each of the formulations
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  Levels of IVIVC LevelA Level B Level C Multiple Level C Level D
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  Level A Point topoint correlation exists between invitro and invivo data It is highest level of correlation %drug absorbed calculated by Method of Residual, Wagner-Nelson Method , Loo-Reigelman method 0 10 20 30 40 50 60 70 80 90 100 0 20 40 60 80 100 120 %drugabsorbed %drug dissolved
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  It depends onstatistical moment analysis Mean dissolution time invitro( MDT vitro) compared with mean dissolution time( MDT vivo) or residence time invivo (MRT) 0 10 20 30 40 50 60 70 80 90 100 0 20 40 60 80 100 120 Meanresistancetime(hr) Mean dissolution time(hr) Level B
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  Level C Level Ccorrelation relates one dissolution time point (t50% , t90%,etc.) to one mean pharmacokinetic parameter such as AUC, tmax or Cmax. This is the weakest level of correlation as partial relationship between absorption and dissolution is established as it does not represent the entire shape of plasma concentration-time curve.
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  Multiple Level C Relationshipbetween one or more pharmacokinetic parameters of interest (Cmax, AUC, or any other suitable parameters) and amount of drug dissolved at several time point of dissolution profile Multiple Level C correlation should be based on at least three dissolution time points covering the early, middle, and late stages of the dissolution profile
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  Level D It isa semi quantitative (qualitative analysis) and rank order correlation It is not considered useful for regulatory purpose but can be serves as an aid in the development of a formulation or processing procedure
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  Class Solubility PermeabilityAbsorption Expected IVIVC I High High Gastric emptying controlled IVIVC is expected if dissolution rate is slower than gastric emptying rate, otherwise limited or no correlation II Low High Dissolution controlled IVIVC is expected if in vitro dissolution rate is similar to in vivo dissolution rate, unless dose is very high III High Low Dissolution independent Absorption (permeability) is rate determining; limited or no IVIVC with dissolution rate IV Low Low Case-by- case evaluation Limited or no IVIVC is expected BCS and expected IVIVC for immediate release drug products
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  Class Solubility PermeabilityIVIVC IA High and site independent High & site independent IVIVC Level A expected IB High and site independent Dependent on site & narrow absorption window IVIVC Level C expected IIa Low and site independent High & Site Independent IVIVC Level A expected IIb Low and site independent Dependent on site and narrow absorption window Little or no IVIVC Va Variable Variable Little or no IVIVC Vb Variable Variable IVIVC Level A expected BCS and expected IVIVC for extended-release drug products
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  Application of IVIVC 3.Formulation assessment: In vitro dissolution 2. In early stages of drug delivery technology development 4. Dissolution specifications 7. Future biowaivers 9. IVIVC - Parenteral drug delivery 1. Application in drug delivery system 5. Formulation assessment: In vitro dissolution 6. Biowaivers 8. Establishment of dissolution specifications 10. Mapping
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  Some Limitations More thanone dosage form is needed Pharmacokinetics and absorption of the drug should be ‘‘linear.’’ Absorption should not be the limiting factor, if the solubility is not the limiting factor in comparison to the drug release, an IVIVC may be attempted. The release must depend on the formulation, and must be the slowest phenomenon vs. dissolution and absorption.
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  Conclusion The pharmaceutical industriesare in search of a way that can save cost and resources of drug development. IVIVC can serve as surrogate for in vivo bioavailability and to support biowaivers also allows setting the dissolution specification and methods. The substitute of expensive clinical trials with the use of IVIVC is perhaps the most important feature of IVIVC