S. Thairs et al., Effect of dose size, food and surface coating on the gastric residence anddistribution of an ion exchange resin, INT J PHARM, 176(1), 1998, pp. 47-53
Ion exchange resin displays prolonged gastric residence and uniform distrib
ution over the gastric mucosa when given in a small volume of water to fast
ed subjects. The aim of this study was to explore factors which could influ
ence the observed gastric retention, for example the quantity of resin admi
nistered, 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 heal
thy volunteers using gamma scintigraphy to visualize the distribution of th
e resin in the stomach. On the first two occasions each subject received ei
ther a 25 mg or 250 mg dose of cholestyramine (an anionic exchange resin) i
n 1 mi of water. On the last occasion each volunteer received 250 mg of cho
lestyramine coated with the inert polymer ethylcellulose, to determine if t
he 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 a
fter dosing to determine the effects of inducing a fed pattern of motility
on the gastric retention of the resin. Gastric retention was measured as th
e area under the stomach activity-time curve (AUC). Median AUC values (rela
tive 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 1
76.1 for fed subjects. Approximately 20% of the resin persisted in the stom
ach 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 di
stribution of any of the data sets. It can be concluded that the prolonged
gastric residence and uniform distribution of ionic resins is not influence
d by the dose size and that the binding of the dose to the mucosa is suffic
iently strong to retain the dose during feeding 4 h after administration. T
he mechanism by which resin becomes mucoadherent is not clear; however, the
se results indicate that it is unlikely to be due to a charge-based attract
ion. (C) 1998 Elsevier Science B.V. All rights reserved.