Screening Permeability As A Tool In Formulation Selection

By Janice Cacace, Ph.D.

The bioavailability of insoluble compounds remains one of the biggest challenges to drug delivery. While there are strategies that can be applied at lower dosage levels, it is particularly difficult to formulate for improved bioavailability at high dosage levels. Improving bioavailability can be crucial to creating a dosage form that is easy to use and meets requirements for patient compliance.

Bioavailability and its importance

The term bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation. By definition, when a medication is administered intravenously its bioavailability is 100%. However, when a medication is administered via other routes (such as oral), its bioavailability decreases (due to incomplete absorption or first-pass metabolism). The measurement of the amount of the drug in the plasma at periodic time intervals indirectly indicates the rate and extent at which the active pharmaceutical ingredient is absorbed from the drug product and becomes available at the site of action.

Bioavailability can be affected by many things including:

1. Solubility
2. Permeability
3. Stability of the API in the GI tract
4. Membrane transport
5. First pass metabolism

This paper demonstrates how by using membrane flux systems and side by side diffusion cells, CoreRx was able to discern which factors were most important for bioavailability of a model Class IV compound. This enabled them to increase bioavailability of the compound by ~70%.