In an earlier article (link) the mechanism of drug absorption was described considering ionization characteristics of drugs and the differences between the surface areas of the stomach and intestine. The purpose of the article was to explain and highlight how ionization of both an acidic and basic drug will impact in providing undissociated drug molecules both in the stomach and intestine. It is important to note that it is the undissociated drug molecules in the solution form which are responsible, and required, for drug absorption.
The low (acidic) pH of the stomach would favour high undissociated concentrations of acidic drugs compared to high (neutral or basic) pH of the intestine which will favour higher dissociated (ionized) concentrations. The opposite is true for basic drugs where low (acidic) pH of the stomach will result in higher concentrations of ionized or protonated basic drugs in the stomach compared to higher concentrations undissociated drugs in the intestine. The pH of the environments (stomach and intestine) explains only the ionization of drugs (acidic or basic) i.e. comparative availability of undissociated drug molecules in solution form but NOT the EXPECTED absorption of the drugs from these sites. The absorption of drugs, however, can only be explained based on the available surface areas of the stomach and intestine. As the intestine provides a much larger and efficient (permeable) surface, compared to stomach, thus it provides far superior and efficient drug absorption, as explained in the previous article.
It is sometime assumed that as acidic drugs are more readily available in undissociated form in the stomach (low pH) so they will preferentially be absorbed from the stomach, and as basic drugs will be more readily available in undissociated form in the intestine (neutral or higher pH) thus will preferentially be absorbed from the intestine. This assumption is inaccurate, as such a simplistic approach ignores the absorption capacity and differences of surface areas of the stomach and intestine sites. Furthermore, such an assumption i.e. absorption based on pH consideration only, contradicts the observations reported extensively in the literature. For example:
- “The stomach is primarily a processing organ and not an absorptive organ …”. Washington, N., Washington, C., and Wilson, C. Physiological pharmaceutics: Barriers to drug absorption, 2nd ed. CRC Press, 2001. (p. 82)
- “The experimental data available from classical work of Brodie (1964) and more recent studies (Prescott and Nimmo, 1981) are all consistent with the following conclusion: the nonionized form of a drug will be absorbed more rapidly than the ionized form at any particular site in the gastrointestinal tract. However, the rate of absorption of a drug from the intestine will be greater than that from the stomach even if the drug is predominantly ionized in the intestine and largely nonionized in the stomach.” Goodman, L., Gilman, A., and Gilman, A. Goodman and Gilman’s the Pharmacological Basis of Therapeutics. New York: Macmillan, 1985. p. 7.
- “Theoretically, weakly acidic drugs (eg, aspirin) are more readily absorbed from an acid medium (stomach) than are weakly basic drugs (eg, quinidine). However, whether a drug is acidic or basic, most absorption occurs in the small intestine because the surface area is larger and membranes are more permeable.” (Merck Manual)
- “The scintigraphy studies suggest that a sustained release ibuprofen formulation is absorbed throughout the entire GI tract and that the large bowel is the site that demonstrates the greatest proportion of ibuprofen absorption.” Davies N.M. “Clinical Pharmacokinetics of Ibuprofen: The First 30 Years.” Clinical Pharmacokinetics. 1998: 101–154.
- “Ketoprofen, like many other drugs, is mainly absorbed in the small intestine”. Shohin et al. “Biowaiver Monographs for Immediate-release Solid Oral Dosage Forms: Ketoprofen.” Journal of Pharmaceutical Sciences. 2012: 3593–3603.
An important implication of such a physiological process (i.e. drugs absorption from the intestine) is that a dissolution test should also be conducted simulating intestinal environment, e.g. using a dissolution medium having a pH in the range of 5 to 7. Conducting the tests using acidic pH (simulating the stomach environment) may not be considered appropriate in particular when the dissolution results are to be related to the physiological outcome such as plasma drug levels.
