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correlation of invivo data with invitro dissolution data.pptx

This document discusses the correlation of in vivo drug data with in vitro dissolution data. It begins by defining in vitro-in vivo correlation (IVIVC) as a predictive mathematical model relating an in vitro property like dissolution rate to an in vivo response like plasma drug concentration. The objectives of IVIVC include reducing human testing and regulatory burdens. There are different levels of IVIVC - Level A provides the closest correlation while Level D is only qualitative. Level A correlates dissolution directly to absorption rate while Level C relates a parameter like AUC to a dissolution parameter. IVIVC can be used to justify formulation and process changes without additional human studies.

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CORRELATION OF IN-VIVO DATA WITH IN-VITRO DISSOLUTION DATA PRESENTED BY NAVYASHREE G II SEM M PHARMACY DEPT PHARMACEUTICS PRESENTED TO PROF H S KEERTHY DEPT OF PHARMACEUTICS MALLIGE COLLEGE OF PHARMACY 1/18
CONTENTS  Introduction  Objectives  Levels of correlation  Application of IVIVC 2/18
INTRODUCTION  In vitro - In vivo correlation is defined as the predictive mathematical model that describes the relationship between an in-vitro property(such as the rate of dissolution) of a dosage form and an in- vivo response( such as the plasma drug concentration).  In vitro property is the rate or extent of drug dissolution or release while , in-vivo response is the plasma drug concentration or amount of drug absorbed. 3/18
 OBJECTIVES 1. Setting up of an in-vitro release test that would serve as a surrogate for in- vivo plasma profiles (bio equivalence testing) 2. To minimize unnecessary human testing. 3. Decreased regulatory burdens. 4. To set up bio pharmaceutically meaningful in-vitro release specifications. 5. Minimization of cost and time required in additional bioavailability studies. 4/18
 LEVELS OF CORRELATION  Four levels of correlation can be found in FDA guidelines.  Each level denotes its ability to predict invivo response of dosage form from its in vitro property.  The higher the level better is the correlation. 1) Level A correlation 2) Level B correlation 3) Level C correlation 4) Multiple level C correlation 5) Level D correlation 5/18
LEVEL A CORRELATION  It represents the relationship between in vitro dissolution and in vivo input rate.  For developing a correlation between two parameters one variable should be common between them. 6/18
 Here the data available is in vitro dissolution profile and in vivo plasma drug concentration profile.  A correlation of this type is generally linear and represents a point to point relationship between in- vitro dissolution and in-vivo input rate.  Advantages of level A correlation  A point to point correlation is developed. The invitro dissolition curve serves as a surrogate for invivo performance. Any change in manufacturing procedure or modification in the formula can be justified without the need for additional human studies.  The invivo dissolution serves as an invivo indicating quality control procedure for predicting dosage form’s performance. 7/18
LEVEL B CORRELATION  It uses the principles of statistical movement analysis.  The mean in-vitro dissolution time is compared either to the mean residence time or the to the mean in-vivo dissolution time.  It doesn’t uniquely reflect the actual in-vivo plasma level curve, because a number of different in-vivo curves will produce similar mean residence time values.  It is the least useful correlation for regulatory purposes. 8/18
 A Level C IVIVC establishes a single point relationship between a dissolution parameter, for example,t50% dissolved in 4 hours and a pharmacokinetic parameter (e.g., AUC, Cmax, Tmax).  A Level C correlation does not reflect the complete shape of the plasma concentration-time curve, which is the critical factor that defines the performance of ER products .  It is helpful in early stages of formulation development when pilot formulations are being selected. 9/18 LEVEL C CORRELATION
 In addition to these three levels, a combination of various levels C is also described: A multiple Level C correlation relates one or several pharmacokinetic parameters of interest to the amount of drug dissolved at several time points of the dissolution profile.  For the establishment of a correlation as described in the FDA guidance, various parameters can be used as presented in following table. 10/18
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MULTIPLE LEVEL C CORRELATION  It reflects the relationship between one or several pharmacokinetic parameters of interest and amount of drug dissolved at various time points of dissolution profile.  It should be based on at least 3 dissolution time points that include an arly, middle and last stage of dissolution. 13/18
LEVEL D CORRELATION  It is a rank order and qualitative analysis and is not considered useful for regulatory purposes.  It is not a formal correlation but serves as an aid in the development of a formulation or processing procedue. 14/18
APPLICATIONS OF IVIVC  To use in in-vitro dissolution study as a surrogate for human BE studies. This will reduce the number of human BE studies during the initial approval process as well as scale up and post approval changes.  Justification for therapeutic product quality.  Enhanced significance of invitro testing.  During scale up, the dissolution data to judge the impact of process changes as well establishing final specifications for dissolution.  The database may be utilized during further scale up and site transfer as well as supporting post approval changes.  It ensure batch to batch consistency in the physiological performance of a drug product. 15/18
UNIVERSITY QUESTIONS  Discuss briefly in-vitro, in-vivo correlation of drug dissolution. ( june 2023) 16/18
REFERENCES 17/18 • A Text book of ADVANCED BIOPHARMACEUTICS AND PHARMACOKINETICS BY PV PUBLICATIONS • SLIDESHARE NOTES
THANK YOU 18/18