Compatibility of cefoperazone sodium and cimetidine hydrochloride in 5% dextrose injection

The compatibility of cimetidine hydrochloride and cefoperazone sodium in 5% dextrose injection stored at two temperatures was studied. Cimetidine hydrochloride and cefoperazone sodium were reconstituted or diluted with 5% dextrose injection to form an admixture with a cimetidine concentration of 2 mg/mL and a cefoperazone concentration of 5 mg/mL. The admixture was stored in 100-mL vented i.v. containers in the dark at 4 and 25 degrees C; three containers were stored at each temperature. A 2-mL sample was taken from each container after 0.5, 0.75, 1, 6, 12, 24, and 48 hours of storage and visually inspected, tested for pH, and assayed by a stability-indicating high-performance liquid chromatographic method. Triplicate studies were done for each storage condition. At both temperatures, drug concentrations varied by less than 5% during the study period. No color change, precipitation, or cloudiness was observed for any of the solutions under any of the storage conditions. Cefoperazone sodium 5.0 mg/mL and cimetidine hydrochloride 2.0 mg/mL in admixtures in 5% dextrose injection are stable for 48 hours at 4 and 25 degrees C.     

Stability of zidovudine in 5% dextrose injection and 0.9% sodium chloride injection

The stability of zidovudine at a concentration of 4 mg/mL in 5% dextrose injection and 0.9% sodium chloride injection in polyvinyl chloride infusion bags stored at room and refrigerated temperatures for up to eight days was studied. Zidovudine was diluted in 5% dextrose injection and in 0.9% sodium chloride injection to a concentration of 4 mg/mL. Six admixtures were prepared with each diluent; three were stored at room temperature (25 +/- 1 degree C) and three were refrigerated (4 +/- 1 degree C). At 0, 3, 6, 24, 48, 72, and 192 hours, 2-mL aliquots were removed. One milliliter of each aliquot was diluted to a zidovudine concentration of approximately 40 micrograms/mL and assayed in duplicate by a stability-indicating high-performance liquid chromatographic method. Visual inspection was performed at each sampling time for precipitation, turbidity, color change, and gas formation. Sample pH was recorded at 0 and 192 hours. In all admixtures, more than 97% of the initial zidovudine concentration remained throughout the study period. No visual or pH changes were observed. Zidovudine 4 mg/mL in admixtures with 5% dextrose injection or 0.9% sodium chloride injection stored in polyvinyl chloride infusion bags was stable for up to 192 hours (eight days) at room temperature and under refrigeration.     

Stability and availability of cyclosporine in 5% dextrose injection or 0.9% sodium chloride injection

The stability of cyclosporine in commonly used i.v. solutions and the percentage of the drug delivered via polyvinyl chloride administration tubing were studied. Cyclosporine injection was prepared according to the manufacturer's instructions and diluted with 5% dextrose injection (D5W) or with 0.9% sodium chloride injection (NS). Admixtures containing cyclosporine 2 mg/mL were prepared in polyvinyl chloride minibags (five for each solution) and in glass containers (three for each solution). The sample obtained at time zero from a glass container protected from light was the control. Additional samples were prepared in minibags and run through 70-inch polyvinyl chloride administration sets. An HPLC assay for cyclosporine was used. Exposure to room light did not significantly affect cyclosporine concentrations. More than 90% of the initial drug concentration remained after 24 hours under all storage conditions, but less than 95% remained after 6 hours in samples diluted with NS and stored in plastic. At times up to 60 minutes, cyclosporine concentrations were significantly different in solutions infused from the minibags through polyvinyl chloride tubing from those in control solutions. Under these conditions, cyclosporine is stable in D5W in glass containers or polyvinyl chloride minibags for 24 hours and in NS for 6 hours (polyvinyl chloride) to 12 hours (glass). However, because of the potential for leaching of plasticizers, cyclosporine admixtures should be stored in glass or used within six hours if stored in polyvinyl chloride minibags. Approximately 10% of the initial drug concentration is lost to 70-inch length polyvinyl chloride infusion tubing.     

Stability of ganciclovir sodium in 5% dextrose injection and in 0.9% sodium chloride injection over 35 days.

The stability of ganciclovir 1 and 5 mg/mL in 5% dextrose injection and in 0.9% sodium chloride injection was studied at 25 degrees C and 5 degrees C over 35 days. Ganciclovir (as the sodium salt) was added to 120 polyvinyl chloride bags containing either 5% dextrose injection or 0.9% sodium chloride injection to attain ganciclovir concentrations of 1 and 5 mg/mL. Thirty bags were prepared for each combination of drug concentration and i.v. solution. Half of the bags in each group were stored at 25 degrees C; the other half were stored at 5 degrees C. Samples withdrawn from all 120 bags immediately after preparation were frozen for later determination of initial concentration. At 7, 14, 21, 28, and 35 days after preparation, approximately 5-mL samples representing each test condition were withdrawn for analysis. The samples were visually examined, tested for pH, and assayed by high-performance liquid chromatography. There was no significant loss of ganciclovir under any of the study conditions over 35 days. All solutions were clear throughout the study period. The pH decreased slightly in both diluents at both ganciclovir concentrations but did not deviate from the manufacturer's range (9-11). Admixtures containing ganciclovir 1 and 5 mg/mL (as the sodium salt) in 5% dextrose injection and 0.9% sodium chloride injection were stable in polyvinyl chloride bags stored at 25 degrees C and 5 degrees C for 35 days.     

Stability and compatibility of ganciclovir sodium in 5% dextrose injection over 35 days.

The stability and compatibility of ganciclovir sodium in 5% dextrose injection over 35 days were assessed. Nine admixtures of ganciclovir sodium 1, 5, and 10 mg/mL in 5% dextrose injection were aseptically prepared. Immediately thereafter, six samples were aseptically withdrawn from each admixture into sterile collection tubes. Three of the samples were frozen for stability-indicating high-performance liquid chromatographic (HPLC) assay at a later date, and the other three were immediately assessed for pH. Each admixture was also assessed visually for color change, turbidity, gas evolution, and precipitation. The admixtures were stored in the dark at 4-8 degrees C and sampled at 10 and 35 days. There was no significant loss of ganciclovir over the 35-day study period. No admixture at any time contained less than 93.4% or more than 103.7% of its initial ganciclovir concentration. There were no appreciable pH changes, and there was no evidence of visual incompatibility. Ganciclovir sodium 1, 5, and 10 mg/mL in 5% dextrose injection was stable for at least 35 days when stored in the dark at 4-8 degrees C.     

Activity of urokinase diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored in glass or plastic syringes

The effects of the diluent, the container, the i.v. set, and the drug concentration on the adsorption of urokinase to i.v. administration systems were studied, along with the compatibility of urokinase with plastic and glass syringes. Solutions of urokinase 1500 and 5000 IU/mL in 0.9% sodium chloride injection and 5% dextrose injection in glass and polyvinyl chloride (PVC) containers were sampled at 2 and 30 minutes. Administration sets were attached to PVC containers containing the urokinase-5% dextrose injection solutions, and samples were collected at 90 and 150 minutes. Glass and polypropylene syringes containing urokinase 5000 IU/mL in 0.9% sodium chloride injection or 5% dextrose injection were sampled at 0, 4, 8, and 24 hours. Urokinase activity was measured by an in vitro clot lysis assay. No urokinase diluted in 0.9% sodium chloride injection adsorbed to glass or PVC containers. For urokinase 1500 IU/mL in 5% dextrose injection, a loss of 15% to 20% occurred almost instantaneously in PVC containers; additional losses to the infusion sets were minimal. However, for urokinase 5000 IU/mL in 5% dextrose injection, no losses were observed in the PVC systems. No drug loss to glass bottles was seen for urokinase 1500 or 5000 IU/mL in 5% dextrose injection. Urokinase potency remained constant in polypropylene and glass syringes for 24 hours. To minimize urokinase sorption to PVC containers, higher concentrations of urokinase diluted in 5% dextrose injection should be used, provided that clinical safety and efficacy are not compromised. The use of 0.9% sodium chloride injection as a diluent also prevents sorption losses.     

Stability of procainamide hydrochloride in neutralized 5% dextrose injection

The stability of procainamide hydrochloride in neutralized 5% dextrose injection was studied. Sixty-four admixtures were prepared by adding either 2 mL (for 0.4% admixtures) or 4 mL (for 0.8% admixtures) of procainamide hydrochloride to 250 mL of 5% dextrose injection in plastic containers. The pH of 32 of these admixtures (16 of each type) was adjusted to 7.5. These 32 admixtures represented the neutralized group, and the remaining 32 represented the control group. The admixtures were stored at either 23-25 degrees C (room temperature) or 5 degrees C (refrigeration) for 24 hours. Procainamide hydrochloride concentrations in each sample were determined by high-performance liquid chromatography immediately after the admixtures were prepared and at various intervals during storage. Procainamide concentrations decreased over time in 5% dextrose injection. The decrease was significantly less for admixtures in neutralized 5% dextrose injection, those stored under refrigeration, and those with an 0.8% concentration of drug. Decreases in procainamide hydrochloride concentrations in the control admixtures might have been caused by procainamide-dextrose complexation. Initial concentrations of procainamide hydrochloride in 5% dextrose injection can be adequately maintained over a 24-hour storage period by neutralizing the 5% dextrose injection or storing the admixture at 5 degrees C. However, because it is impractical to maintain the necessary temperature condition during a 24-hour infusion, neutralization might be the most viable alternative when extended stability of procainamide hydrochloride in 5% dextrose injection is required.     

Stability of pentamidine isethionate in 5% dextrose and 0.9% sodium chloride injections

The stability of pentamidine isethionate in small-volume intravenous admixtures was studied. In an initial experiment, duplicate admixtures containing pentamidine 1 or 2 mg/mL were prepared using 100 mL each of 5% dextrose injection and 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags. All solutions were kept at room temperature and were assayed at various times up to 48 hours by high-performance liquid chromatography. Solutions were also examined visually and tested for pH at each assay time. In a second experiment, single admixtures containing pentamidine 2 mg/mL were prepared in 100-mL PVC bags of both 5% dextrose injection and 0.9% sodium chloride injection. After time-zero determinations of pentamidine concentration, pH, and visual clarity, solutions were allowed to run through PVC infusion sets at 20 mL/hr. Samples were collected at the distal end of each set at various times up to five hours for analysis of pentamidine concentration, pH, and clarity. All admixtures in the initial experiment retained greater than 90% of initial concentration for the 48-hour study period. However, 5% dextrose admixtures infused through PVC administration sets showed a loss in initial concentration of about 2%, while 0.9% sodium chloride admixtures lost about 10% of initial concentration after infusion through these sets. The pH of all solutions in both experiments varied by less than 0.5 units, and no particulate matter or color change was noted in any of the admixtures. In the concentrations and diluents studied, pentamidine appears to be stable for 48 hours in PVC bags. Slight losses in the initial concentrations of these solutions after infusing them through PVC infusion sets may be caused by adsorption to the set.     

Stability of vancomycin hydrochloride in 5% dextrose and 0.9% sodium chloride injections

The stability of vancomycin hydrochloride mixed with 5% dextrose and 0.9% sodium chloride injections was studied. Vancomycin hydrochloride powder was mixed with each of the two diluents in final concentrations of 5 mg/mL. Duplicate samples of each admixture were divided into four parts and stored at 24 degrees C in glass and in plastic i.v. bags for 17 days and at 5 degrees C and -10 degrees C in glass for 63 days. To additional samples, hydrochloric acid or phosphate buffer was added; these were stored at 24 degrees C for 17 days. At various storage times, clarity and pH of the samples were recorded and vancomycin concentrations were measured in triplicate by high-performance liquid chromatography. Except for the buffered samples, all solutions remained clear and pH was unchanged. Vancomycin concentrations decreased less than 6% during 17 days at room temperature. In the refrigerated and frozen samples, vancomycin concentrations decreased less than 1% throughout the study. Vancomycin hydrochloride is stable in admixtures with 5% dextrose injection and 0.9% sodium chloride injection for 17 days at 24 degrees C and for 63 days at 5 degrees C and -10 degrees C.     

Stability of ganciclovir sodium (DHPG sodium) in 5% dextrose or 0.9% sodium chloride injections

The stability of 9-[(1,3-dihydroxy-2-propoxymethyl]) guanine sodium (ganciclovir sodium, also known as DHPG sodium) in two infusion solutions was studied. Lyophilized ganciclovir sodium 500 mg was reconstituted with sterile water 10 mL to give a theoretical concentration of 50 mg/mL. After reconstitution, 6-mL aliquots of the solution were added to 100 mL of 0.9% sodium chloride injection or 5% dextrose injection in polyvinyl chloride i.v. bags. One sample was withdrawn from each of 10 bags of each solution and analyzed by high-performance liquid chromatography (HPLC). Thirty bags of each solution were then stored under each of the following conditions: at room temperature under laboratory light, at room temperature in the dark, and under refrigeration for up to five days. Single potency assays were performed by HPLC on each of three bags of solution at three and five days after initial dilution of the solutions. The solutions were visually inspected, and the pH of the solutions was measured. All solutions of ganciclovir were stable for at least five days under all storage conditions; mean ganciclovir concentrations did not drop below 98% of initial theoretical values throughout the storage period. No important changes in the pH of the solutions occurred during the study period. Under the conditions of this study, ganciclovir sodium is stable for up to five days when prepared in 5% dextrose injection or 0.9% sodium chloride injection.     

Compatibility of cisplatin and fluorouracil in 0.9% sodium chloride injection

The effect of drug concentration and light on the compatibility and stability of cisplatin and fluorouracil in i.v. admixtures was studied. Two sets of admixtures were prepared in 0.9% sodium chloride injection in polyvinyl chloride bags--(1) cisplatin 200 micrograms/mL and fluorouracil 1,000 micrograms/mL and (2) cisplatin 500 micrograms/mL and fluorouracil 10,000 micrograms/mL. Half of the admixtures were protected from light. All admixtures were stored at room temperature (24-26 degrees C), and those admixtures not protected from light were stored under room fluorescent light. After visual inspection, the pH of each admixture was determined, and an aliquot was assayed for drug concentration using a stability-indicating high-performance liquid chromatographic assay. Over a four-hour period, no visual changes were observed and the pH changes observed were negligible. In admixtures containing the lower concentrations of cisplatin and fluorouracil, it took approximately 1.5 hours for the concentration of cisplatin to reach 90% of the initial concentration. By four hours (lower concentration range) and three hours (higher concentration range) after the admixtures were prepared, less than 75% of the initial cisplatin concentration remained. There was less than a 5% decrease measured in the fluorouracil concentrations over the observation time. Admixtures of cisplatin and fluorouracil in 0.9% sodium chloride injection at the concentrations evaluated in this study must be used within one hour of preparation, whether or not they are protected from light. Intravenous administration of fluorouracil and cisplatin by continuous infusion will require alternative approaches to mixing the two drugs in the same container.     

Stability of milrinone in 0.45% sodium chloride, 0.9% sodium chloride, or 5% dextrose injections

The stability of milrinone in 0.45% and 0.9% sodium chloride injections and in 5% dextrose injection in glass and plastic containers was studied. Admixtures containing milrinone 0.2 mg/mL were prepared in three 500-mL glass containers, three 500-mL polyethylpolypropyl copolymer plastic containers, and three 1-L flexible plastic containers of each solution. Milrinone content was determined by high-performance liquid chromatography at intervals during 72 hours of storage at room temperature; one sample of each solution and container type was protected from light. Duplicate assays of each sample were performed, and samples were observed for visual and pH changes. In all samples milrinone concentrations were more than 97% of the initial concentration. No changes in pH or appearance occurred. Milrinone at a concentration of 0.2 mg/mL is stable for 72 hours at room temperature in 0.45% and 0.9% sodium chloride injections and in 5% dextrose injection in glass or plastic containers.