Effect of resin surface charge on gastric mucoadhesion and residence of cholestyramine

Previous studies performed on excised gastric tissue and in healthy volunte ers revealed that the ion exchange resin, cholestyramine, exhibits mucoadhe lent behaviour. This study was designed to elucidate whether surface charge affected this behaviour. Gamma scintigraphy was performed on fasted normal subjects following oral administration of cholestyramine or the cationic e xchanger Amberlite(R) IRP-69, either uncoated or polymer-coated to mask the ir charge. Subjects were fed after 4 h. The initial gastric emptying of all formulations was similar (T-50 values (mean +/- S.E.M.): cholestyramine = 85.86 +/- 9.16 min; IRP-69 = 76.09 +/- 9.23 min, polymer-coated cholestyram ine = 72.0 +/- 12.64 min; polymer-coated IRP-69 = 70.25 +/- 10.57 min: P = 0.724). However, after 3 h the emptying pattern of cholestyramine was slowe r than that of IRP-69. This resulted in greater retention limes than IRP-69 (AUC(0-6) values (relative units)= 15200 +/- 1093 versus 9352 +/- 811, cho lestyramine versus IRP-69: P = 0.0004). This effect was reduced by polymer- coating the cholestyramine. Serial images showed that cholestyramine was tr apped in the orophalyngeal region and subsequently displaced by the meal, r esulting in higher levels of activity remaining at 6 h. Thus, cholestyramin e exhibited prolonged gastric residence via mucoadhesion and was distribute d throughout the stomach. The surface charge of the resin was found to have a contributory role. These materials may have potential for the delivery o f drugs in the topical treatment of the gastric mucosa, for example in the eradication of Helicobacter pylori. (C) 2000 Elsevier Science B.V. All righ ts reserved.