Gastroretentive Floating-Bioadhesive Drug Delivery System for Rebamipide: Design, In vitro and In vivo Evaluation

Abstract

Rebamipide is an amino acid analog of 2-(1H)-quinolinone used in the treatment of peptic ulcer. Here we sought to formulate and evaluate gastroretentive floating-bioadhesive tablets of rebamipide to increase the gastric residence time and further compare their pharmacokinetics with conventional immediate release tablets. Floating-bioadhesive tablets of rebamipide were prepared with combination of Polyox WSR 303 and CP 971P/HPMC K4M and Sodium CMC by direct compression method. The prepared formulations were evaluated for hardness, thickness, weight variation, friability, drug content, in vitro buoyancy and drug release. The optimized formulation (RBF12) floated with a lag time of 28.3 ± 3.2 sec, duration of floating 12 h and released about 99.91 ± 1.84% of drug in 12 h, and then followed non-Fickian diffusion release mechanism with n value of 0.635. The RBF12 tablets with BaSO4 remained in stomach for 5.13 ± 0.64 h (n=3) in radiological studies. The formulation, RBF12 exhibited maximum bioadhesive strength (1.346 ± 0.110 N) than other formulations. The bioavailability studies were carried out for the optimized formulation (RBF12) and compared with that of reference IR tablets “Rebagen” in nine healthy human volunteers. Based on in vivo performance significant difference was observed between Cmax, tmax, t1/2, AUC0–∞, and MRT of RBF12 and IR tablets. The increase in relative bioavailability of RBF12 was 1.7-fold when compared to reference IR tablets. The increased relative oral bioavailability may be due to the floating-bioadhesive mechanism of dosage form, which is desirable for drugs absorbed from the upper part of gastrointestinal tract.