Comparative scintigraphic assessment of the intragastric distribution and residence of cholestyramine, Carbopol 934P and sucralfate

It has been demonstrated that orally administered cholestyramine is distrib uted throughout the stomach and provides prolonged gastric residence via mu coadhesion. Gamma scintigraphy was used to compare the gastric emptying and residence of this resin with two formulations known to exhibit retentive o r bioadhesive properties, Carbopol 934P and sucralfate. Fasted normal subje cts received a single radiolabelled dose and gastrointestinal transit was m onitored for 6 h. The subjects were fed after 4 h to determine the effects of inducing a fed pattern of motility on the retention of the formulations. Initial gastric emptying was similar (Mean T-50 +/- S.E.M.: cholestyramine = 66.93 +/- 9.39 min; Carbopol = 56.57 +/- 11.96 min; sucralfate = 48.33 /- 11.07 min; P = 0.548. n = 10), however, the emptying of cholestyramine s lowed beyond 2 h. This resulted in greater residence for cholestyramine (Me an AUC(0-6) +/- S.E.M. (relative units) = 11516 +/- 686 versus 7657 +/- 117 0 versus 6170 +/- 998; cholestyramine versus Carbopol versus sucralfate; P = 0.004: n = 10), with approximately 25% remaining in the stomach at 6 h co mpared to 3.84 and 2.65% of Carbopol and sucralfate, respectively. Cholesty ramine was also distributed widely throughout the stomach whereas Carbopol and sucralfate were concentrated in the body and antrum. Thus, as cholestyr amine had a comparable emptying time to Carbopol and sucralfate but greater gastric residence and wider distribution, it could provide a potential muc oadhesive drug delivery system targeting the gastric mucosa far treatment o f conditions such as Helicobacter pylori infection. (C) 2001 Elsevier Scien ce B.V. All rights reserved.