In vitro In vivo correlation

In vitro In vivo correlation

1. In Vitro- In Vivo Correlation ( IVIVC ) Presented By: Mahewash A. Pathan 1

2. Introduction The term of IVIVC was first introduced in the late 1950 by Wagner et al . USP definition of IVIVC: “ The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, & a physicochemical property or characteristic of the same dosage form .” FDA definition of IVIVC: “A predictive mathematical model describing the relationship between an in-vitro property of a dosage form & an in-vivo response.” 2

3. Importance To serve as a surrogate for in-vivo bioavailability. To support biowaivers foe bioequivalence testing. To validate the use of dissolution methods & set the dissolution specifications. IVIVC proves an important research tool in the development of drug delivery system. The IVIVC model facilitates the rational development & evaluation of immediate or extended release dosage forms. Hence it acts as a tool for formulation screening. To assist quality control for certain scale-up & post approval changes (SUPAC). Reduction of regulatory burden. To reduce the number of human studies during the formulation development. 3

4. Approaches for IVIVC Correlation based on plasma level data Based on urinary excretion data Based on pharmacologic response 4

5. Levels of IVIVC 5

6. Level In vitro In vivo A Dissolution curve Absorption curve B Mean Dissolution Time (MDT) Mean Residence Time (MRT), MAT. C Disintegration time, dissolution rate, dissolution efficiency Cmax, Tmax, Ka, AUC. D Rank order or qualitative analysis Not useful for regulatory considerations but for formulation & process development. 6

7. IVIVC Models Convolution model Deconvolution model 7

8. Types of correlation 1. Quantitative correlation 8 Y = mx + c Where, y = in vivo parameter X = in vitro parameter m = slope of the relationship c = intercept. Ideally m = 1 & c = 0, indicating a linear relationship. 2. Rank order correlation

9. IVIVC development 9

10. Validation of IVIVC Model   Internal External Prediction error For Cmax %Prediction error (P.E.)= ( Cmax Observed – Cmax Predicted ) / Cmax Observed * 100 For AUC: %Prediction error (P.E.)= (AUC observed – AUC predicted )/ AUC observed * 100   10

11. Biopharmaceutics classification system (BCS) 11

12. Application of IVIVC Application in drug delivery system In early stages of drug delivery technology development Formulation assessment: In vitro dissolution Dissolution specifications Future biowaivers IVIVC - Parenteral drug delivery Biowaivers Establishment of dissolution specifications Mapping 12

13. 13

14. references Somnath Sakore and Bhaswat Chakraborty, In Vitro – In Vivo Correlation : A strategic Tool in Drug Development, Journal of Bioequivalence & Bioavailability, 2011. Amitava Ghosh, Gopal Kumar Choudhury, In vitro- In vivo Correlation : A Review, Journal of Pharmacy Research 2009. Jean- Michel Cardot, In vitro in vivo correlation basis and application to slow release injectable formulation, A review, Farmacia, 2015, vol. 63, 6. J. M. Cardot, E. Beyssac and M. Alric, In Vitro- In Vivo Correlation: Importance of Dissolution in IVIVC, Dissolution Technologies, February 2007. Nattee Sirisuth et al, In-Vitro-In-Vivo Correlation Definitions and Regulatory Guidance, International Journal of Generic Drugs. D.M. Brahmankar, Sunil B. Jaiswal, Biophaemaceutics and pharmacokinetics A treatise, Vallabh Prakashan, Page No. 292-293. 14

15. THANK YOU 15