Cimetidine hydrochloride compatibility. III: Room temperature stability in drug admixtures.

The stability of cimetidine hydrochloride mixed in intravenous solutions individually with 37 additives was investigated. Recommended doses of cimetidine hydrochloride injection and the other additives were diluted aseptically in varying concentrations in compatible intravenous solutions. The admixtures were stored at room temperature for 24 hours. Initial and 24-hour samples were evaluated visually on the basis of color, clarity, and pH. Cimetidine content was determined with a high-pressure liquid chromatographic procedure. The following drugs formed a precipitate with some dilutions of cimetidine hydrochloride injection in i.v. solutions: amphotericin B, cefamandole nafate, cefazolin sodium, and cephalothin sodium. The combination of cimetidine hydrochloride (300 mg) and cephalothin sodium (100 mg) resulted in a cimetidine concentration that was 77% of theory. Cimetidine hydrochloride injection was visually and chemically stable in the other admixtures examined. The results of this investigation suggest that incompatibility may be expected when cimetidine hydrochloride is combined with some antibiotics, and cimetidine incompatibilities may be concentration dependent.

Cimetidine hydrochloride compatibility. II: room temperature stability in intravenous infusion fluids.

The visual compatibility and chemical stability of cimetidine hydrochloride diluted in 19 intravenous infusion fluids were investigated. Cimetidine hydrochloride injection was added aseptically to large-volume parenteral solutions at concentrations of 120 and 500 mg/100 ml. Cimetidine concentration was analyzed by high-pressure liquid chromatography initially and after storage periods of 24, 48, 72, and 168 hours at room temperature. Cimetidine hydrochloride in each of the dilutions remained visually compatible for one week, exhibiting no changes in color, clarity, or odor; pH values remained constant. The addition of cimetidine to Normosol-R pH 7.4 resulted in solutions having pH values of 6.3 and 6.0 at 120 and 500 mg/100 ml, respectively. Cimetidine remained chemically stable in each of the intravenous fluids studied. Cimetidine hydrochloride is visually and chemically stable for at least one week when added to the intravenous fluids studied at concentrations of 120 and 500 mg/100 ml and stored at ambient room temperature.

Cimetidine hydrochloride compatibility. I: Chemical aspects and room temperature stability in intravenous infusion fluids.

The visual and chemical stabilities of cimetidine hydrochloride in solution with frequently prescribed large-volume parenteral fluids were studied. Cimetidine hydrochloride was added aseptically to each of 22 intravenous fluid products in glass or polyvinyl chloride containers to final concentrations of 120 and 500 mg/100 ml. The solutions were stored at approximately 25 degrees C. At 0, 24, 48, 72, and 168 hours (1 week) after mixing, the solutions were examined for color, odor, and clarity; pH values were measured; and the cimetidine contents were determined by high-pressure liquid chromatography. The solutions showed no changes in odor, color, or clarity. The pH values remained relatively invariant, except for slight increases in the 5% dextrose and in the Aminosyn 3.5% M solutions (120 mg/100 ml) and the 10% Travert Injection (500 mg/100 ml). Cimetidine content remained steady in all solutions. Cimetidine hydrochloride is visually and chemically stable for at least one week at ambient temperatures when combined with commonly used intravenous fluids in concentrations of 120 and 500 mg/100 of solution.

The influence of food on nitrofurantoin bioavailability.

The effect of food on the absorption of five commercial dosage forms of nitrofurantoin varying widely in drug release and dissolution characteristics was assessed in man after oral administration. Four healthy fasting and nonfasting male subjects received, in a crossover fashion, a single 100-mg dose of microcrystalline nitrofurantoin as an aqueous suspension, three different compressed tablets, and a single 100-mg dose of macrocrystalline nitrofurantoin in a capsule. Both the absorption and the duration of therapeutic urinary concentrations of nitrofurantoin were significantly increased after administration of the five products to nonfasting subjects. The enhancement in the bioavailability of the drug in the presence of food ranged from 20% to 400%, with the greatest absorption-enhancing effect occurring with those dosage forms exhibiting the poorest dissolution characteristics. It is concluded that single-dose comparative bioavailability studies of drug products normally administered with food should be performed in both nonfasting and fasting subjects.