Physiological and Pharmacokinetic Factors Affecting Performance of Sustained Release Dosage Forms

Abstract

Among many workers in the drug formulation area, there is the mistaken notion that an oral product which releases drug at an idealized rate in vivo will result in drug blood levels which are relatively constant over the duration of the dosing interval. Unfortunately, intra-and inter-subject variability in physiological processes virtually ensures that under clinical conditions this will not be the case. Some of the many factors involved include: (1) differing rates of absorption dependent upon the site of drug release in the gut; (2) gastrointestinal motility and transit times, particularly gastric emptying; (3) the presence of food in the gut; (4) gastrointestinal blood flow; (5) disease and drug induced effects on gut physiology; and (6) the nature of the microflora in the large intestine

From a pharmacokinetic view, the blood levels of drugs which are more rapidly eliminated from the body will be more sensitive to this gastrointestinal variability than those which are more slowly eliminated. Consequently, the level of success that may be expected from a sustained release product i s inversely proportional t o the therapeutic need for such a product