Formulation development and evaluation of a novel bi-dependent clarithromycin gastroretentive drug delivery system using Box-Behnken design

Abstract

Helicobacter pylori is the main representative of gastritis, gastrointestinal ulcers, and gastric carcinoma. Therefore its suppression is a precondition for treatment of gastric and duodenal complications. The objective of present work was to develop a novel bi-dependent gastroretentive tablet (BDGRT) formulation containing clarithromycin and to evaluate pharmacokinetics in beagle dogs. Bi-dependent gastroretentive tablets were effectively developed using both sublimation material and effervescent agent. BDGRT formulation was optimized using 3-level-3-factor, Box-Behnken experimental design. The selected independent variables were amount of HPMC K4M (X1), NaHCO3 (X2), and camphor (X3). The dependent variables were Floating lag time (YFLT), % friability (YFR), tablet crushing strength (YTCS) and %Cumulative drug release at 5th h (YQ5) & at 10th h (YQ10). Floating properties of tablets was affected by sublimation of camphor. The predicted responses by the optimization model were 13.05 Sec, 0.990%, 3.52 kg/cm2, 51.29%, and 86.32% for YFLT, YFR, YTCS, YQ5 and YQ10 respectively with X1, X2 and X3 of 119.76 mg, 10.66% and 11.69% respectively. The optimized BDGRT also evaluated for surface morphology, compatibility and stability studies. The delayed tmax, increased Mean residence time of BDGRT believed it can be a competent tool for effective delivery of clarithromycin for the eradication of H. pylori.