title: In vitro methods can forecast the effects of intragastric residence on dosage form performance.
abstract: Intragastric conditions can affect the performance of solid dosage forms. For two cases, the ability of in vitro methods to forecast these effects was investigated: first, the ability of cholestyramine to sequester bile salts in the fed small intestine and, second, disintegration times of hard gelatin capsules. After incubating cholestyramine for 90 min in milk gradually digested with pepsin, the binding of taurocholates from fed state simulating intestinal fluid onto the resin became non-specific and the affinity constant was reduced from 220 l/mole (without prior incubation) to 60 l/mole. These data are consistent with the comparatively poor performance of cholestyramine products when administered in the fed state. Scintigraphic studies showed that intragastric disintegration times of hard gelatin capsules are delayed in both the fasted and fed states according to the degree of cross-linking. These results were satisfactorily predicted by the in vitro disintegration times in fasted state simulating gastric fluid and in milk gradually digested with pepsin, whereas results were poorly predicted in compendial media. This work illustrates that recently proposed methods for simulating intragastric environment may be useful in predicting the performance of solid dosage forms.
authors.affiliation: Laboratory of Biopharmaceutics and Pharmacokinetics, National & Kapodistrian University of Athens, Panepistimiopolis, 157 71 Zografou, Athens, Greece.
authors.forename: Lida
authors.initials: L
authors.lastname: Kalantzi
authors.forename: Richard
authors.initials: R
authors.lastname: Page
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Nicolaides
authors.forename: George
authors.initials: G
authors.lastname: Digenis
authors.forename: Christos
authors.initials: C
authors.lastname: Reppas
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry*; D002214:Capsules; D002792:Cholestyramine Resin / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D018565:Food-Drug Interactions; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry; D011237:Predictive Value of Tests; D012995:Solubility; D013270:Stomach; D013656:Taurocholic Acid / Q000737:chemistry
chemical_list: D001647:Bile Acids and Salts; D002214:Capsules; D003432:Cross-Linking Reagents; D004364:Pharmaceutical Preparations; D002792:Cholestyramine Resin; D013656:Taurocholic Acid; D005780:Gelatin