Effect of dose size, food and surface coating on the gastric residence and distribution of an ion exchange resin

Abstract Ion exchange resin displays prolonged gastric residence and uniform distribution over the gastric mucosa when given in a small volume of water to fasted subjects. The aim of this study was to explore factors which could influence the observed gastric retention, for example the quantity of resin administered, the fed state of the subject, and the surface charge of the resin. The study was performed as a single blind, three-way crossover in 12 healthy volunteers using gamma scintigraphy to visualize the distribution of the resin in the stomach. On the first two occasions each subject received either a 25 mg or 250 mg dose of cholestyramine (an anionic exchange resin) in 1 ml of water. On the last occasion each volunteer received 250 mg of cholestyramine coated with the inert polymer ethylcellulose, to determine if the gastric residence of the resin was influenced by the surface properties of the particles. For all formulations, half of the subjects were fed 4 h after dosing to determine the effects of inducing a fed pattern of motility on the gastric retention of the resin. Gastric retention was measured as the area under the stomach activity–time curve (AUC). Median AUC values (relative units) for the 25 mg, 250 mg and polymer coated 250 mg doses were 139.6, 199.6 and 146.0 respectively, for fasted subjects and 164.1, 256.9 and 176.1 for fed subjects. Approximately 20% of the resin persisted in the stomach for the entire 6 h of the study in every case, and this was distributed evenly throughout the fundus, body and antrum. Statistical analysis of the data showed no significant differences between the gastric emptying and distribution of any of the data sets. It can be concluded that the prolonged gastric residence and uniform distribution of ionic resins is not influenced by the dose size and that the binding of the dose to the mucosa is sufficiently strong to retain the dose during feeding 4 h after administration. The mechanism by which resin becomes mucoadherent is not clear; however, these results indicate that it is unlikely to be due to a charge-based attraction.