In-Vitro-In-Vivo Correlation (IVIVC)

• IVIVC is a predictive mathematical model that links in-vitro drug dissolution with in-vivo pharmacokinetic performance.

• It helps estimate drug behavior in the body based on laboratory dissolution data, aiding in formulation development, regulatory approvals, and quality control.

Applications of IVIVC

1. Formulation Development & Optimization – Predicts in-vivo drug performance using in-vitro dissolution data, reducing the need for extensive in-vivo studies.

2. Scale-Up & Post-Approval Changes – Assesses the impact of manufacturing changes without requiring new in-vivo studies.

3. Biowaivers – Supports bioequivalence waivers for modified-release formulations by demonstrating similar in-vitro dissolution profiles.

4. Quality Control – Establishes dissolution specifications as a surrogate for in-vivo performance, ensuring consistent therapeutic efficacy.

Developing an IVIVC Model

1. Obtain in-vitro dissolution data under physiologically relevant conditions.

2. Collect in-vivo pharmacokinetic data (e.g., plasma drug concentration over time).

3. Analyze correlations between in-vitro and in-vivo data.

4. Develop a mathematical model to relate dissolution and pharmacokinetics.

5. Validate the IVIVC model by comparing predictions with actual in-vivo results.

Types of IVIVC Correlations

1) Quantitative Linear IVIVC

• Establishes a linear relationship between in-vitro dissolution and in-vivo pharmacokinetic parameters (e.g., AUC, Cmax).

• Expressed as:

• Useful for predicting drug performance but may not apply to all drugs, requiring more complex models in some cases.

2) Correlation Methods

• Plasma Level Correlation – Links in-vitro dissolution to plasma drug concentration profiles (AUC, Cmax, Tmax).

• Urinary Excretion Correlation – Compares dissolution data to cumulative drug excretion in urine, useful when plasma data is difficult to obtain.

• Pharmacological Response Correlation – Relates dissolution to therapeutic effect or biomarker levels.

Levels of IVIVC

1. Level A – Point-to-point linear relationship between in-vitro dissolution and in-vivo absorption rate.

2. Level B – Compares mean dissolution time to mean in-vivo residence time.

3. Level C – Establishes a rank-order relationship between in-vitro dissolution and pharmacokinetic parameters.

4. Multiple Level C – Uses multiple Level C correlations for different pharmacokinetic measures or time points.