ABSORPTION

Absorption is important to discuss with regard to dissolution because in vivo, dissolution occurs in a permeable GI tract, whereas dissolution testing is usually done in an impermeable glass vessel. Characterizing absorption using parameters such as an absorption rate constant or permeability provide an essential link between dissolution and what happens to the drug once it has been absorbed, and necessary to establish a predictable in vitro/in vivo correlation. Absorption is an area of common interest to both formulation and pharmacokinetic scientists because it affects the decisions that both groups make. In Equations 2 and 3, drug absorption was characterized as drug leaving the GI lumen. This is a common way to study absorption. For example, both rat and human intestinal perfusion experiments have been used to characterize absorption by isolating a segment of the intestine and using the difference in drug concentration entering and leaving the segment to calculate an absorption rate constant or permeability. When done properly to ensure that drug degradation or water absorption and secretion are not affecting the results, characterizing absorption in this way is a reliable method. Another method to study absorption would be to use drug blood concentrations after intravenous and oral dosing to calculate an absorption rate constant. This method is more complicated because metabolism must be taken into account. For example, it would be possible for a drug to be completely absorbedacross the GI membrane, but entirely metabolized by the liver before reaching thesystemic circulation. Unless all drug metabolites were traced, one might erroneously assume that because the drug itself was not detected in the blood, thatabsorption had not occurred. This situation is important to recognize so that aformulation group does not waste time attempting to improve absorption whenmetabolism is the real problem.Throughout this chapter, both the term absorption rate constant andpermeability will be used interchangeably. The term permeability has the advantage that it is shorter and perhaps more descriptive. Both absorption rate constantsand permeability are not like other physical parameters that might be found in thescientific literature. Their values have a rather large degree of error typical of pharmacokinetic parameters and may vary in the GI tract due to positionalchanges in anatomy and environmental conditions. The term absorption rateconstant has been criticized because the name implies something that it is not.However, in practice, permeability is also usually treated as if it were a constant.The absorption rate constant has the advantage of having the characteristics of afirst-order rate constant. Given its value, one can quickly take the natural logarithm of two and divide it by the absorption rate constant to calculate an absorptionhalf-life. In effect, permeability is usually converted to a first-order rate constant for calculations that require the calculation of mass of drug absorbed.