Biopharmaceutics Classification System

The transport model considered in this book, based on permeability and solubility, is also found in the biopharmaceutics classification system (BCS) proposed by the U.S. Food and Drug Administration (FDA) as a bioavailability-bioequivalence (BA/BE) regulatory guideline [101-110]. The BCS allows estimation of the likely contributions of three major factors—dissolution, solubility, and intestinal permeability—which affect oral drug absorption from immediate-release solid oral products. Figure 2.9 shows the four BCS classes, based on high and low designations of solubility and permeability. The draft document posted on the FDA website details the methods for determining the classifications [106]. If a molecule is classed as highly soluble, highly permeable (class 1), and does not have a narrow therapeutic index, it may qualify for a waiver of the very expensive BA/BE clinical testing.

The solubility scale is defined in terms of the volume (mL) of water required to dissolve the highest dose strength at the lowest solubility in the pH 1 -8 range, with 250 mL as the dividing line between high and low. So, high solubility refers to complete dissolution of the highest dose in 250 mL in the pH range 1-8. Permeability is the major rate-controlling step when absorption kinetics from the GIT is controlled

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