Biopharmaceutical Aspects of Aspirin-Induced Gastrointestinal Blood Loss in Man

Abstract

The extent of injury of the gastrointestinal mucosa due to contact with aspirin (ASA) particles is likely to be a function of contact area and duration of contact, among other factors. While the duration of contact between ASA particles and mucosa may be shortened by decreasing the particle size of the drug and thereby increasing its rate of dissolution, this results in an increased area of contact between the drug and the mucosa. It is impossible to decrease both duration and area of contact by particle size adjustment. One method by which contact time can be shortened, without simultaneously increasing the area of contact, is the addition of antacids (“buffers”) to ASA tablet formulations. Other formulation variables being the same, these additives should increase the rate of ASA dissolution and thereby decrease the time of contact between the drug particles and the gastrointestinal mucosa. Average daily occult blood loss in the stool was determined in healthy human subjects who received different ASA tablet preparations. Two of these preparations were very similar in their in vivo absorption characteristics, but differed in that one contained relatively small particles of ASA and no antacids, while the other type contained larger ASA particles and antacids. The ASA-antacid tablets produced significantly less bleeding than the ASA tablets which did not contain the additives.