In vitro- in vivo correlation's dissolution limits setting

Area of Science:

• Pharmaceutical Sciences
• Biopharmaceutics
• Drug Development

Background:

• In vitro-in vivo correlation (IVIVC) is crucial for formulation development and can replace in vivo studies.
• Validated IVIVC enables setting dissolution limits, serving as a surrogate for in vivo testing.

Purpose of the Study:

• To investigate and compare various methods for establishing dissolution limits.
• To evaluate the impact of different calculation approaches and variability on dissolution limit setting.

Main Methods:

• Comparison of classical ±10% dissolution limits with recommended ±10% Cmax/AUC and a novel 90% CI back-calculation method.
• Simulation of pharmacokinetic processes and variability to assess method influence.

Main Results:

• Different methods yield varying results, suggesting specific rules for limit setting.
• The 90% CI back-calculation method is accurate and advantageous for drugs with low intra-individual variability.
• IVIVC is generally not recommended for highly variable drugs, aligning with findings.

Conclusions:

• The 90% CI approach accounts for intra-subject variability, increasing the likelihood of demonstrating bioequivalence (BE).
• This method allows for broader in vitro dissolution limits compared to traditional approaches when intra-subject variability is reasonable.
• It supports setting more robust dissolution specifications in pharmaceutical development.