In-Vitro-In-Vivo Correlation (IVIVC)

In Vitro In Vivo Correlation IVIVC links drug dissolution data with bioavailability to predict absorption and therapeutic performance.

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:
     $\text{In-vivo parameter} = a \times \text{In-vitro dissolution} + b$ 
     • 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.

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