Novel gastroretentive dosage forms: evaluation of gastroretentivity and its effect on riboflavin absorption in dogs.
OBJECTIVE
[corrected] The purpose of this study was to design novel gastroretentive dosage forms (GRDFs) based on unfolding multilayer polymeric films, to investigate the mechanism of their gastroretentivity in dogs, and to assess the effect of compounding a narrow absorption window drug in a GRDF on the drug's absorption properties.


METHODS
Dosage forms (DFs) with different dimensions and mechanical properties were administered to beagle dogs with acidic buffer (pH = 1.5), whose gastric retention time (GRT) was then determined by X-ray pictures. Concurrent administration of radiopaque markers was used to assess the effect of the GRDF and/or acidic buffer on GRT. The absorption of riboflavin from a prototype GRDF was compared with a nongastroretentive controlled-release DF and to an oral solution of the drug.


RESULTS
Large DFs (> or = 2.5 x 2.5 cm) containing rigid frame had prolonged GRT (>4 h). Administration of 400 mL of acidic buffer (or water) prolonged GRT whereas the GRDF did not cause additional prolongation. The extended absorption phase (>48 h) of riboflavin administered in a GRDF led to 4-fold increased bioavailability.


CONCLUSIONS
The combination of large dimensions with rigidity produce gastroretentivity that can be used to improve absorption properties of a model of narrow absorption window drugs in the gastrointestinal tract.
Klausner
Eytan A
EA
Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Israel.
Lavy
Eran
E
Stepensky
David
D
Friedman
Michael
M
Hoffman
Amnon
A
D000818:Animals; D004285:Dogs; D004304:Dosage Forms; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D012256:Riboflavin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013270:Stomach / Q000187:drug effects
D004304:Dosage Forms; D012256:Riboflavin