Oral drug absorption rate-limiting processes

Usually, an increase in Cg that would affect the dissolution rate would occur only when another process, such as membrane transport or stomach emptying, becomes the rate-limiting step in drug absorption. As a general rule pharmacists should advise patients to take their oral medications with a full glass of water to ensure that dissolution occurs under optimal conditions. 

Furthermore, pharmacokinetic administration, distribution, metabolism and excretion (ADME) factors affect drug bioavailability, efficacy and safety, and, thus, are a vital consideration in the selection process of oral drug candidates in development pipelines. Since solubility, permeability, and the fraction of dose absorbed are fundamental BCS parameters that affect ADME, these BCS parameters should prove useful in drug discovery and development. In particular, the classification can used to make the development process more efficient.For example, in the case of a drug placed in BCS Class II where dissolution is the rate-limiting step to absorption, formulation principles such as polymorph selection, salt selection, complex formation, and particle size reduction (i.e., nanoparticles) could be applied earlier in development to improve bioavailability. 

With very few exceptions, dissolution of the drug substance in the GI tract milieu is a prerequisite for drug absorption following oral administration. For Class II compounds, the rate-limiting factor in their intestinal absorption is dissolution /solubility [23-25]. Hence, in-depth understanding of this process is essential in the oral delivery of low-solubility compounds. Factors governing the dissolution process can be directly identified from the following equation, based on the Nernst-Brunner and Levich modifications of the Noyes-Whitney model [26-28] ... 

It is highly desirable in drug discovery and early drug development to predict the influence of the drug dissolution on oral absorption on the basis of rather simple measurements of dissolution or solubility [2,14]. The primary variable for judgments of in vivo absorption is the dissolution rate rather than the solubility. Drug dissolution can be the rate-limiting step in the absorption process and thereby affect the rate of... 

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