Gastrointestinal Dissolution and Absorption of Class II Drugs

Modern drug discovery techniques (i.e., advances in in vitro high-throughput screening methods, the introduction of combinatorial chemistry) have resulted in 

When Fick s first law is applied to a membrane, the absorption of a drug across the GI mucosal surface under sink conditions can be written as 

The absorption number (An) is the ratio of permeability (Peff) and the intestinal radius (P) multiplied by the residence time (t,.es), which can be interpreted as the effective absorption rate constant (t. ) times the residence time  

The dissolution number (Dn) is the ratio of the residence time and the dissolution time (toiss)j which comprises the equilibrium solubility (Cs), diffusivity (D), density (p), the initial particle radius (r0), and the intestinal residence time (tres)  

Finally, the dose number (D0) is the ratio of dose to dissolved drug  

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The second situation when IVIVC is not likely for class II drugs is where the absorption is limited by the saturation solubility in the gastrointestinal tract rather than the dissolution rate, as discussed in more detail above. In this situation, the drug concentration in the gastrointestinal tract will be close to the saturation solubility, and changes of the dissolution rate will not affect the plasma concentrationtime profile and in vivo bioavailability. Standard in vitro dissolution tests are carried out under sink conditions , i.e., at concentrations well below the saturation solubility. Thus, only effects related to dissolution rate can be predicted in vitro. If more physiologically relevant dissolution media are used, which do not necessarily provide sink conditions , the possibility for IVIVC could be improved, as has been indicated by the results of recent studies using simulated intestinal medium [76],... 

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