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Compatibility of premixed theophylline and methylprednisolone sodium succinate intravenous admixtures.

The stability of theophylline supplied as a premixed injection and of methylprednisolone sodium succinate in admixtures containing both drugs was studied. Solutions containing theophylline in concentrations of 4.0 mg/mL and 0.4 mg/mL were used. Methylprednisolone sodium succinate was added to each solution to produce a final concentration of 0.5 mg/mL and 2.0 mg/mL of methylprednisolone alcohol, a pharmacologically active form of methylprednisolone sodium succinate. Each admixture was prepared in triplicate, and samples were kept at room temperature in glass containers. Immediately after admixture and at 3, 6, 12, and 24 hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline concentration and for both methylprednisolone sodium succinate and methylprednisolone alcohol content. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The addition of theophylline in 5% dextrose injection to the methylprednisolone sodium succinate solutions resulted in decreased pH values for all solutions, which did not vary significantly throughout the study period. Theophylline concentrations did not change significantly compared with baseline. In solutions containing theophylline 0.4 mg/mL with either 2.0 or 0.5 mg/mL of methylprednisolone sodium succinate, less than 90% of the initial methylprednisolone sodium succinate concentrations remained at 24 hours. However, within three hours after admixture preparation, methylprednisolone alcohol was detected in those solutions in increasing concentrations. A commercial preparation of premixed theophylline in 5% dextrose injection in a concentration of 4 mg/mL or less can be mixed with methylprednisolone sodium succinate in a final concentration of 2 mg/mL or less and administered intravenously within 24 hours after mixing.

Chromatography, High Pressure Liquid↗

Compatibility of premixed theophylline and verapamil intravenous admixtures.

The stability of verapamil hydrochloride injection when mixed with a commercial product of premixed theophylline in 5% dextrose injection was studied. Solutions containing theophylline in concentrations of 4.0 and 0.4 mg/mL were used. Verapamil hydrochloride was added to each theophylline solution to produce final verapamil concentrations of 0.4 mg/mL and 0.1 mg/mL. Each admixture was prepared in triplicate, and samples were kept at room temperature in glass. Immediately after mixing and at 4, 8, 12, and 24 hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline and verapamil concentrations. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The addition of the verapamil hydrochloride injection to the theophylline in 5% dextrose injection resulted in decreased mean pH values of 4.29 and 4.37 for all solutions compared with 4.80 and 4.90 for the verapamil control samples at concentrations of 0.4 and 0.1 mg/mL. These values did not vary significantly throughout the study period. Theophylline and verapamil concentrations did not change significantly compared with baseline or control solutions during the study period. Verapamil hydrochloride injection in final concentrations of 0.1 to 0.4 mg/mL can be added to a commercial preparation of premixed theophylline in 5% dextrose injection in concentrations of 0.4 to 4.0 mg/mL and administered intravenously within 24 hours of mixing without loss of potency of either drug.

Chromatography, High Pressure Liquid↗

Compatibility of imipenem-cilastatin sodium with commonly used intravenous solutions.

The stability of imipenem-cilastatin sodium (Primaxin, Merck Sharp & Dohme) in various intravenous fluids was determined after storage at 4 degrees C or 25 degrees C and after freezing. Samples of imipenem-cilastatin sodium were constituted with 100 mL of each of 17 i.v. fluids to concentrations of 2.5 mg/mL or 5.0 mg/mL of each drug component and stored in glass infusion bottles at constant room temperature (25 degrees C) or constant refrigerated temperature (4 degrees C). The concentration of each solution was determined immediately after constitution by a stability-indicating high-performance liquid chromatographic assay; the concentrations of both drugs were monitored in each i.v. fluid until the time that the concentration of either imipenem or cilastatin decreased to less than 90% of the initial concentration (t90). The exact value of t90 was determined for each solution by linear regression. The solutions were also assessed for changes in pH or color. Cilastatin sodium was more stable in all 17 i.v. fluids than imipenem. The stability of imipenem was dependent on the concentration of that drug in solution; solutions of imipenem 2.5 mg/mL were more stable than solutions of imipenem 5.0 mg/mL. The values of t90 for imipenem in solutions stored at 4 degrees C were greater than the values for solutions stored at 25 degrees C. Imipenem was most stable in 0.9% sodium chloride injection. The pH values of the solutions generally decreased during the study period.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗

Compatibility of aminophylline and methylprednisolone sodium succinate intravenous admixtures.

The stability of aminophylline and methylprednisolone sodium succinate in admixtures containing both drugs was studied. Admixtures containing aminophylline 1.0 mg/mL and methylprednisolone sodium succinate 2.0 and 0.5 mg/mL were prepared in both 5% dextrose injection and 0.9% sodium chloride injection. Each admixture was prepared in triplicate and samples were kept at room temperature in glass. Immediately after admixture and at one, two, and three hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline concentration and for both methylprednisolone sodium succinate and methylprednisolone alcohol. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The admixtures had higher pH values after aminophylline was added, but pH of the samples did not change significantly. Aminophylline concentrations did not change significantly throughout the study period. In 0.9% sodium chloride admixtures with methylprednisolone sodium succinate 0.5 mg/mL, less than 90% of the initial methylprednisolone concentration remained at two hours at the 2.0 mg/mL initial concentration, less than 90% remained at three hours. However, methylprednisolone alcohol (a pharmacologically active form of methylprednisolone sodium succinate) was detected in increasing concentrations after the first hour. Aminophylline in a final concentration of 1.0 mg/mL or less can be mixed with methylprednisolone sodium succinate in a final concentration of 2.0 mg/mL or less in 5% dextrose injection or 0.9% sodium chloride injection and administered intravenously within three hours after mixing.

Aminophylline↗

Stability of morphine sulfate and meperidine hydrochloride in a parenteral nutrient formulation.

The compatibility, stability, and availability of morphine sulfate and meperidine hydrochloride prepared in total parenteral nutrient (TPN) solution, 5% dextrose injection, and sterile water for injection in polyvinyl chloride (PVC) bags were evaluated. A 300-mg dose of each narcotic was mixed in 0.25-L bags of 5% dextrose injection and sterile water for injection, and in 3-L bags of TPN and sterile water for injection. Each solution was examined visually for precipitation, color change, turbidity, and the evolution of gas immediately after the addition of the drug to the bag and every 12 hours for a 36-hour period. Narcotic concentrations in each solution were determined by high-pressure liquid chromatography before and for 36 hours after the addition of the drugs to the bags. No loss of either drug because of adsorption to the PVC bags was found. Morphine sulfate and meperidine hydrochloride were chemically compatible and stable in TPN and 5% dextrose injection for 36 hours. Solutions of morphine sulfate or meperidine hydrochloride in PVC bags containing TPN or 5% dextrose injection are visually and chemically compatible, as well as stable and available for 36 hours when stored at 21.5 degrees C with no protection from environmental light.

Chemistry, Pharmaceutical↗

Compatibility of clindamycin phosphate with cefotaxime sodium or netilmicin sulfate in small-volume admixtures.

The stability and compatibility of clindamycin phosphate plus either cefotaxime sodium or netilmicin sulfate in small-volume intravenous admixtures were studied. Admixtures containing each drug alone and two-drug admixtures of clindamycin phosphate plus cefotaxime sodium or netilmicin sulfate were prepared in 100 mL of 5% dextrose injection and 0.9% sodium chloride injection in both glass bottles and polyvinyl chloride (PVC) bags. Final concentrations of clindamycin, cefotaxime, and netilmicin were 9, 20, and 3 mg/mL, respectively. All solutions were prepared in duplicate and stored at room temperature (24 +/- 2 degrees C). Samples were visually inspected, tested for pH, and assayed for antibiotic concentration using stability-indicating assays at 0, 1, 4, 8, 16, and 24 hours for admixtures in glass bottles and at 0, 8, and 24 hours for admixtures in PVC bags. No substantial changes in color, clarity, pH, or drug concentration were observed in any of the solutions. Clindamycin phosphate is compatible with cefotaxime sodium or netilmicin sulfate in 5% dextrose and 0.9% sodium chloride injections in glass bottles or PVC bags for 24 hours.

Cefotaxime↗

Availability of insulin from parenteral nutrient solutions.

The effect of the following variables on insulin loss from total parenteral nutrient solutions was examined: (1) time of infusion sample; (2) insulin concentration; (3) amino acid or polypeptide source; (4) electrolytes and vitamins; (5) inline filters; (6) glass and polyvinyl chloride (PVC) infusion containers; and (7) human albumin. I125-tagged insulin was added to various parenteral nutrient solutions in liter containers. These solutions were prepared and drained to simulate actual clinical use. The drained solutions were collected and measured for radioactivity, and the percent of insulin remaining in the infusion container was calculated. Basic solutions of amino acids and protein hydrolysates in dextrose with 30 units of insulin failed to deliver approximately 44 to 47% of the added insulin. Varying the concentration of insulin had a small but statistically significant effect on the degree of insulin loss. The use of inline filters and PVC bags caused an even greater loss of insulin. The addition of albumin or electrolytes and vitamins decreased the insulin loss.

Absorption↗