Τίτλος:
In vitro methods can forecast the effects of intragastric residence on dosage form performance
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2008 Elsevier B.V. All rights reserved.
Συγγραφείς:
Kalantzi, L.
Page, R.
Nicolaides, E.
Digenis, G.
Reppas, C.
Περιοδικό:
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Λέξεις-κλειδιά:
bile salt; colestyramine; gelatin; pepsin A; resin; taurocholic acid, article; binding affinity; cross linking; diet restriction; drug dosage form; feeding; in vitro study; incubation time; intestine fluid; performance; prediction; priority journal; scintigraphy; small intestine; stomach juice, Bile Acids and Salts; Capsules; Cholestyramine; Cross-Linking Reagents; Food-Drug Interactions; Gelatin; Humans; Hydrogen-Ion Concentration; Intestine, Small; Models, Biological; Pharmaceutical Preparations; Predictive Value of Tests; Solubility; Stomach; Taurocholic Acid
DOI:
10.1016/j.ejps.2008.01.014