Question

Under which of the following conditions in-vitro-in-vivo correlation for a drug fails?

• A. When the drug’s absorption takes place by a complex
• B. When the dissolution medium is adequately simulated
• C. When the drug is highly soluble
• D. When the drug is highly permeable but poorly soluble

Answer 1

The Correct Option is C

To understand why in-vitro-in-vivo correlation (IVIVC) for a drug might fail under certain conditions, we need to consider the factors impacting the relationship between the drug's dissolution (in vitro) and absorption (in vivo).

A valid IVIVC means that the drug's dissolution profile (observed in laboratory testing) closely matches its absorption profile within the body, allowing us to predict how a drug behaves pharmacokinetically based on in vitro testing alone.

• Condition: When the drug's absorption takes place by a complex mechanism: This could introduce variability as complex mechanisms (like site-specific absorption or carrier-mediated transport) may not be accurately reflected in standard dissolution tests, but does not inherently guarantee failure of IVIVC.
• Condition: When the dissolution medium is adequately simulated: Proper simulation of the dissolution medium is crucial for establishing IVIVC, as this would support a good correlation rather than cause it to fail.
• Condition: When the drug is highly soluble: Highly soluble drugs often dissolve quickly, resulting in immediate absorption that may not require in-depth IVIVC as the dissolution process isn't the rate-limiting step. This makes IVIVC redundant or unnecessary, hence associated with failure.
• Condition: When the drug is highly permeable but poorly soluble: Also known as BCS Class II drugs, these are the ideal candidates for IVIVC because the dissolution is the rate-limiting step, making in vitro solubility studies relevant for predicting in vivo behavior.

Conclusion: Therefore, the best option is when the drug is highly soluble. In such cases, the drug’s fast dissolution might lead to rapid absorption, which could make it difficult to develop a discernible correlation between in vitro dissolution and in vivo absorption profiles.