Stability of metronidazole, tetracycline HCl and famotidine alone and in combination

Metronidazole, tetracycline HCI and famotidine are commonly used for the treatment of Helicobacter pylori-associated peptic ulcer. In this paper, stabilities of these drugs and their combinations in solid and liquid states were studied as part of preformulation in the development of a combination drug delivery system. Solubility studies of metronidazole and tetracycline HCI were investigated, which indicated that both metronidazole and tetracycline HCI have high solubilities at and around pH 2.0. Metronidazole is relatively stable with little degradation in liquid phase. Tetracycline HCI in the dry state is stable when stored at room temperature regardless of exposure to light or humidity in the range of 20-65%. Enhanced temperature associated humidity effect was responsible for the instabilities of tetracycline HCI and famotidine to different extents. Elevated temperature accelerated the degradation of all the drugs in liquid phase but light exposure was not a factor for the degradation. The degradation processes of tetracycline HCI and famotidine were highly dependent on the pH of the solution, and relatively stable profiles were achieved at pH 4.0. No potential incompatibility between the drugs under storage conditions was observed in the development of a new multi-drug delivery tablet. (C) 2004 Elsevier B.V. All rights reserved.