Effect of resin surface charge on gastric mucoadhesion and residence of cholestyramine.
Previous studies performed on excised gastric tissue and in healthy volunteers revealed that the ion exchange resin, cholestyramine, exhibits mucoadherent 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 exchanger Amberlite(R) IRP-69, either uncoated or polymer-coated to mask their 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 cholestyramine=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 slower than that of IRP-69. This resulted in greater retention times than IRP-69 (AUC(0-6) values (relative units)=15,200+/-1093 versus 9452+/-811; cholestyramine versus IRP-69: P=0.0004). This effect was reduced by polymer-coating the cholestyramine. Serial images showed that cholestyramine was trapped in the oropharyngeal region and subsequently displaced by the meal, resulting in higher levels of activity remaining at 6 h. Thus, cholestyramine exhibited prolonged gastric residence via mucoadhesion and was distributed throughout the stomach. The surface charge of the resin was found to have a contributory role. These materials may have potential for the delivery of drugs in the topical treatment of the gastric mucosa, for example in the eradication of Helicobacter pylori.
Jackson
S J
SJ
Department of Surgery, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK. sarah.jackson@mrc-hnr.cam.ac.uk
Bush
D
D
Washington
N
N
Perkins
A C
AC
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000837:Anion Exchange Resins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002792:Cholestyramine Resin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism*; D016481:Helicobacter Infections / Q000188:drug therapy; D016480:Helicobacter pylori / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011108:Polymers / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000837:Anion Exchange Resins; D011108:Polymers; D002792:Cholestyramine Resin