Effect of pharmaceutical excipients on aqueous stability of rabeprazole sodium.

ABSTRACT

The chemical stability of a proton-pump inhibitor, rabeprazole sodium, was evaluated in simulated intestinal fluid (pH 6.8) containing various 'Generally Recognized As Safe (GRAS)'-listed excipients, including Brij 58, Poloxamer 188, Cremophor RH40, Gelucire 44/14 and PEG 6000. After incubation at 37 and 60 degrees C, the amounts of rabeprazole and its degradation product, thioether-rabeprazole, were quantitated by HPLC analysis. The main degradation product was separated and characterized by LC/MS. The degradation of rabeprazole followed first-order kinetics. In the absence of any excipients, the rate constants (k) obtained at 37 and 60 degrees C were 0.75 and 2.78h(-1), respectively. In contrast, the addition of excipients improved its stability. Among several excipients tested in this study, Brij 58 displayed the greatest stabilizing effect. For instance, at 37 and 60 degrees C, Brij 58 reduced the k values to 0.22 and 0.53h(-1), respectively. The stabilizing mechanisms of these hydrophilic polymeric excipients with optimal HLB values could be partially explained in terms of their solubilizing efficiency and micellar formation for thioether-rabeprazole. In conclusion, rabeprazole formulations that contain suitable excipients would improve its stability in the intestinal tract, thereby maximizing bioavailability.