Permeation

Following dissolution of solid drug into solution, the next step of the oral absorption process is permeation across the intestinal wall. The permeation rate is governed by the following equation:

Permeation Rate = dXdi!solved = Peff x SA x DC (3.5) dt where Peff is the effective permeability of the drug to the intestinal membrane, SA is the surface area available for intestinal permeation, and DC is the concentration gradient across the intestinal membrane.

3.2.3.1 Permeability

Permeability is often assessed using in vitro models such as Caco-2 cells or in situ models such as the perfused rat intestine. Chapter 4 on transporters provides more details on assessment of permeability.

3.2.3.2 Surface Area

The absorption of drug occurs largely in the small intestine. The small intestine is the segment of the gastrointestinal tract that provides the largest surface area for absorption due to its numerous folds, villi, and microvilli.

3.2.3.3 Concentration Gradient

The concentration gradient that drives intestinal permeation is dependent on factors such as the dissolution rate, which controls the amount of drug in solution in the intestinal lumen, and the inherent solubility of the drug in intestinal fluid. In most cases, the plasma drug concentrations are much lower than the concentration of dissolved drug in the intestinal lumen. As a consequence, the permeation process for most drugs occurs under "sink" conditions, making dissolution the rate-limiting step for oral absorption.

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