Stability of fentanyl citrate and bupivacaine hydrochloride in portable pump reservoirs

The stability of fentanyl citrate and bupivacaine hydrochloride in an admixture with 0.9% sodium chloride injection in portable pump reservoirs with or without overwraps was investigated. Twelve 100-mL samples containing fentanyl 20 micrograms/mL and bupivacaine hydrochloride 1250 micrograms/mL were placed in the plastic drug reservoirs, and 1-mL quantities were withdrawn immediately after preparation and at intervals during 30 days of storage. Six reservoirs were refrigerated (3 degrees C) and six stored at room temperature (23 degrees C); three at each temperature were placed in overwraps. All samples were observed for precipitation and for change in color or pH and were analyzed for drug concentration by high-performance liquid chromatography. No precipitation or change in color or pH was observed during the 30-day storage period. No loss of fentanyl or bupivacaine was detected in either the wrapped or the unwrapped samples. Fentanyl citrate and bupivacaine hydrochloride in 0.9% sodium chloride injection appear to be compatible, and admixtures containing the two drugs at the concentrations studied can be stored without overwraps for up to 30 days at refrigerated or room temperature without any significant loss of potency.     

Stability of fentanyl citrate in glass and plastic containers and in a patient-controlled delivery system

This study determined the stability of fentanyl citrate stored in glass or polyvinyl chloride containers and the concentrations of fentanyl citrate delivered by the Janssen on-demand analgesic computer (ODAC) system. Solutions containing 500 micrograms of fentanyl citrate (10 mL) were added to 100-mL three glass containers each of 5% dextrose injection or 0.9% sodium chloride injection and to three 100-mL polyvinyl chloride containers of 5% dextrose injection or 0.9% sodium chloride injection. All containers were stored under usual light conditions and at room temperature. Samples were taken immediately and at 0.25, 0.5, 1, 6, 12, 24, 36, and 48 hours. To determine the concentration of fentanyl delivered via the ODAC system, fentanyl citrate injection 2500 micrograms (50 mL) was added to a 500-mL polyvinyl chloride bag containing 5% dextrose injection. The solution was connected to the ODAC system, and samples of bolus demand doses were collected at various times during a 30-hour period. All the samples were assayed by a stability-indicating gas-liquid chromatographic method. For both glass and plastic containers, the mean +/- S.D. recovery of fentanyl after 48 hours was 98.6 +/- 2.3% when the drug was diluted in 5% dextrose injection and 97 +/- 1.5% when the drug was diluted in 0.9% sodium chloride injection. There was no significant difference between the amount of fentanyl recovered from glass containers and the amount recovered from polyvinyl chloride containers. Nor was there any significant difference between the amount of fentanyl recovered from solutions containing 5% dextrose injection and the amount recovered from solutions containing 0.9% sodium chloride injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of ondansetron hydrochloride in portable infusion-pump reservoirs.

The stability of ondansetron hydrochloride 0.24 and 2 mg/mL when delivered by portable infusion pump at near-body temperature over various time periods was investigated. Nine 100-mL drug reservoirs were prepared, three containing ondansetron hydrochloride 2 mg/mL and six containing ondansetron hydrochloride diluted with 0.9% sodium chloride injection to 0.24 mg/mL. Three of the reservoirs containing the diluted solution were refrigerated for up to 30 days at 3 degrees C before being attached to portable infusion pumps and pumped over 24 hours at 30 degrees C. The remaining six reservoirs were attached to pumps immediately after being filled, and the solutions were delivered for up to 24 hours (the diluted solution; three reservoirs) or up to seven days (the concentrated solution; three reservoirs) at 30 degrees C. Samples were taken initially and periodically and analyzed by high-performance liquid chromatography and with a pH meter. Both the diluted and the concentrated solutions of ondansetron hydrochloride retained at least 95% of the initial drug concentration under all the conditions studied. There was no appreciable change in pH. Ondansetron hydrochloride 0.24 mg/mL was stable when stored for up to 30 days at 3 degrees C and infused over 24 hours at 30 degrees C. Ondansetron hydrochloride 2 mg/mL was stable when infused for up to one week at 30 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.     

Effect of glucose 5% solution and bupivacaine hydrochloride on absorption of sufentanil citrate in a portable pump reservoir during storage and simulated infusion by an epidural catheter

The stability of sufentanil (5 g/ml as citrate) in admixtures with glucose 5% or bupivacaine hydrochloride (2 mg/ml) in 100 ml polyvinyl chloride portable pump reservoirs was investigated during simulated infusion by an epidural catheter at 32°C for 48 h and during storage at 4°C and 32°C for 30 days. During both experiments a small decrease (<5%) in concentration of sufentanil and bupivacaine was observed. No loss of sufentanil or bupivacaine could be detected (in both experiments) in the portable pump reservoirs when stored at 4°C for 30 days. A significant decrease of sufentanil was observed when stored at 32°C after 30 days when diluted with glucose (9.2%) or in combination with bupivacaine (8.9%); also, the bupivacaine concentration decreased significantly (4.7%). It is concluded that sufentanil in portable pump reservoirs can be used under patient conditions at 32°C for 7 days when diluted with glucose 5% or 3 days in combination with bupivacaine hydrochloride.     

Stability of amphotericin B in four concentrations of dextrose injection.

The stability of amphotericin B in 5%, 10%, 15%, and 20% dextrose injection was investigated. The dextrose solutions were prepared in triplicate from sterile water for injection and 70% dextrose injection and placed in empty 50-mL polyvinyl chloride bags. The pH of each solution was determined before amphotericin B was added to a concentration of approximately 100 micrograms/mL. The bags were stored at 15-25 degrees C and protected from light. Three 1-mL samples were taken from each bag at various times up to 24 hours. One sample was analyzed for precipitation and color and pH changes. Two samples were analyzed in duplicate by stability-indicating high-performance liquid chromatography. No visual changes were observed, and pH did not change substantially. The mean amphotericin B concentration was greater than 90% of the initial concentration at each sampling time. However, the drug concentration in 3 of the 27 samples from the admixtures with 10% dextrose injection and 5 of the 27 samples from the admixtures with 20% dextrose injection fell below 90% of the initial concentration. Amphotericin B 100 micrograms/mL was stable in 5%, 10%, 15%, and 20% dextrose injection when stored for up to 24 hours at 15-25 degrees C and protected from light.     

Stability of morphine sulfate in portable pump reservoirs during storage and simulated administration

The stability of four concentrations of morphine sulfate injection in prefilled reservoirs for portable infusion pumps was studied after storage for 30 days at refrigerated and room temperature and after a three-day simulated administration period at body temperature. Thirty-milliliter samples of morphine sulfate injections in four concentrations--1, 5, 15, and 25 mg/mL--were loaded into a pump reservoir. The reservoirs were stored in the dark at 5 degrees C and 25 degrees C for 30 days. Samples were taken from each reservoir immediately after loading and after 7, 14, and 30 days of storage. The reservoirs were then connected to portable infusion pumps, which were run for three days at a flow rate of 0.4 mL/hr at 37 degrees C. The last sample was collected at the end of the three-day period. Samples were assayed for morphine sulfate content by high-performance liquid chromatography. The concentration of morphine sulfate increased up to 6% (for the 5-mg/mL sample) at refrigerated temperature and up to 16% (for the 15-mg/mL sample) at room temperature after 30 days' storage in the reservoirs. Evaporation of water from the reservoirs may have accounted for this phenomenon. No absolute relationship was found between the initial concentration of morphine sulfate and the percentage concentration increase after storage for 30 days. The change in morphine sulfate concentration before and after the three-day pumping period was not significant. Injectable solutions of morphine sulfate in concentrations ranging from 1 to 25 mg/mL are stable when stored at refrigerated temperature for 30 days in a prefilled drug reservoir.     

Stability of fluorouracil, cytarabine, or doxorubicin hydrochloride in ethylene vinylacetate portable infusion-pump reservoirs.

The stability of fluorouracil, cytarabine, and doxorubicin hydrochloride in admixtures stored in portable infusion-pump reservoirs was investigated. Admixtures containing fluorouracil 50 or 10 mg/mL, cytarabine 25 or 1.25 mg/mL, or doxorubicin hydrochloride 1.25 or 0.5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were placed in 80-mL ethylene vinylacetate drug reservoirs protected from light, and 1-mL quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 7, 14, and 28 days at 4, 22, or 35 degrees C. For each condition, three samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, color change, and pH. Evaporative water loss from the containers was measured. Fluorouracil was stable at all temperatures for 28 days. Cytarabine was stable for 28 days at 4 and 22 degrees C and for 7 days at 35 degrees C. Doxorubicin hydrochloride was stable for 14 days at 4 and 22 degrees C and for 7 days at 35 degrees C. No color change or precipitation was observed, and pH values were stable. Loss of water through the reservoirs was substantial only at 35 degrees C for 28 days. When stored in ethylene vinylacetate portable infusion-pump reservoirs, fluorouracil, cytarabine, and doxorubicin hydrochloride were each stable for at least one week at temperatures up to 35 degrees C. Cytarabine and doxorubicin hydrochloride showed decreasing stability at longer storage times and higher temperatures.     

Stability of phenylephrine hydrochloride injection in polypropylene syringes.

PURPOSE: The stability of extemporaneously prepared phenylephrine hydrochloride injection stored in polypropylene syringes was studied. METHODS: Dilution of phenylephrine hydrochloride to a nominal concentration of 100 mug/mL was performed under aseptic conditions by adding 100 mg of phenylephrine hydrochloride (total of 10 mL from two 5-mL 10-mg/mL vials) to 1000 mL of 0.9% sodium chloride injection. The resulting solution was drawn into 10-mL polypropylene syringes and sealed with syringe caps. The syringes were then frozen (-20 degrees C), refrigerated (3-5 degrees C), or kept at room temperature (23-25 degrees C). Four samples of each preparation were analyzed on days 0, 7, 15, 21, and 30. Physical stability was assessed by visual examination. The pH of each syringe was also measured at each time point. Sterility of the samples was not assessed. Chemical stability of phenylephrine hydrochloride was evaluated using high-performance liquid chromatography. To demonstrate the stability-indicating nature of the assay, forced degradation of phenylephrine was conducted. Samples were considered stable if there was less than 10% degradation of the initial concentration. RESULTS: Phenylephrine hydrochloride diluted to 100 microg/mL with 0.9% sodium chloride injection was physically stable throughout the study. No precipitation was observed. Minimal to no degradation was observed over the 30-day study period. CONCLUSION: Phenylephrine hydrochloride diluted to a concentration of 100 mug/mL in 0.9% sodium chloride injection was stable for at least 30 days when stored in polypropylene syringes at -20 degrees C, 3-5 degrees C, and 23-25 degrees C.     

Stability and compatibility of reconstituted ertapenem with commonly used i.v. infusion and coinfusion solutions.

PURPOSE: The stability of ertapenem sodium in various commonly used i.v. infusion solutions and its compatibility with coinfusion solutions was studied. METHODS: Ertapenem was reconstituted with sterile water for injection and then diluted with various commercial i.v. infusion solutions to concentrations of 10 and 20 mg/mL. The solutions were stored in flexible polyvinyl chloride containers at 4 and 25 degrees C and in sterile glass vials at -20 degrees C. The drug's stability at 4 degrees C was monitored daily for up to 10 days, at 25 degrees C at appropriate hourly intervals for up to 30 hours, and at -20 degrees C. The daily for up to 14 days. Compatibility with the coinfusion solutions was monitored for up to eight hours at room temperature. Stability assays were conducted until the ertapenem concentration decreased by 10% or the corresponding degradation products exceeded the approved specifications. Ertapenem concentrations were determined by a stability-indicating high-performance liquid chromatography assay. RESULTS: Ertapenem was more stable in solutions stored at 4 degrees C versus 25 degrees C. Samples frozen at -20 degrees C showed extreme variability. Ertapenem 10 mg/mL was stable for a longer time than at the 20-mg/mL concentration. Ertapenem demonstrated the greatest stability in 0.9% and 0.225% sodium chloride solutions. CONCLUSION: Ertapenem sodium injection 10 and 20 mg/mL are relatively stable in sodium chloride injections and Ringer's solution when stored at 25 and 4 degrees C, but are unstable in mannitol and dextrose solutions. The drug can be coinfused with hetastarch, heparin sodium, and potassium chloride over several hours.     

Stability of sufentanil citrate in a portable pump reservoir, a glass container and a polyethylene container

The stability of sufentanil citrate (100 ml, 5g/ml) in an admixture with sodium chloride 0.9% injection was investigated when filled in a portable pump reservoir with PVC wall, a glass container and a polyethylene container, at 32°C, 4°C and –20°C for up to 21 days. No change in colour was visually observed in any of the samples during the 21-day storage period. A slight precipitation was noticed in three out of nine portable pump reservoirs, one at each storage temperature. There was a slight rise in pH at each storage temperature in all samples. There was approximately 13% loss of sufentanil citrate in the portable pump reservoirs stored at 32°C during 2 days and 60% loss after 21 days, due to absorption of sufentanil citrate in the reservoir wall. No loss of sufentanil citrate could be detected in the portable pump reservoirs when stored at –20°C and 4°C. However, a serious inhomogeneity of the sufentanil citrate solution occurred after thawing at room temperature in the portable pump reservoirs which had been kept at –20°C. The homogeneity could be restored by shaking for approximately 10 min. There was no change in the sufentanil citrate concentrations in the glass containers and polyethylene containers stored at the three temperatures. The portable pump reservoirs stored at 32°C also showed a significant loss of vehicle due to evaporation (1.0±0.1 ml a week). This could not be detected in any of the other samples.     

Effect of pH on absorption of sufentanil citrate in a portable pump reservoir during storage and administration under simulated epidural conditions

Sufentanil (5g/ml as citrate) was investigated for its stability when diluted with sodium chloride 0.9%, in 100 ml polyvinyl chloride portable pump reservoirs during administration under simulated epidural conditions at 32°C for 48 h. Sufentanil was absorbed into the polyvinyl chloride, resulting in a reduction of 10.9% of the concentration after 48 h. The absorption of sufentanil (5g/ml as citrate), alone and in combination with bupivacaine hydrochloride (2 mg/ml), was investigated when diluted with sodium chloride 0.9% in combination with a citrate buffer (pH 4.6), in the same reservoirs under similar conditions. There was no loss of sufentanil after 48 h in both experiments. The effect of the pH on the absorption of sufentanil in polyvinyl chloride was investigated at different pH values. After storage for 21 days at 32°C there was 5.1% loss of sufentanil at pH 4 and 80.6% loss at pH 6. The citrate buffer at the optimum pH (4.6) has a low, acceptable buffer capacity for epidural administration.     

Stability of ceftazidime (with arginine) and of cefuroxime sodium in infusion-pump reservoirs.

The stability of ceftazidime (with arginine) and cefuroxime sodium was studied after storage in infusion-pump reservoirs at freezing and refrigerated temperatures and subsequent simulated administration over 24 hours at near-body temperature. Polyvinyl chloride reservoirs and glass vials were filled with ceftazidime (with arginine) or cefuroxime sodium at various concentrations, diluted in sterile water. Three reservoirs each of ceftazidime 30 and 60 mg/mL and of cefuroxime 22.5, 30, 45, and 60 mg/mL were stored for various times and at various temperatures. Three glass vials each of ceftazidime or cefuroxime 30 and 60 mg/mL were stored for 30 days at -20 degrees C, followed by 4 days at 3 degrees C and 24 hours at 30 degrees C. Samples obtained periodically during storage and during simulated administration were analyzed with high-performance liquid chromatography. Both drugs maintained at least 90% of their initial concentration under all of the test conditions except simulated administration at 30 degrees C, during which degradation accelerated. In portable infusion-pump reservoirs, ceftazidime 30 and 60 mg/mL and cefuroxime 30 and 60 mg/mL were stable for 30 days at -20 degrees C followed by 4 days at 3 degrees C; ceftazidime 30 and 60 mg/mL was stable for 10 days at 3 degrees C; and cefuroxime 22.5 and 45 mg/mL was stable for 7 days at 3 degrees C. However, the drugs may need to be administered over less than 24 hours when the pump reservoir is worn on the patient's body.     

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 of cefazolin sodium, cefoxitin sodium, ceftazidime, and penicillin G sodium in portable pump reservoirs

The stability of cefazolin sodium, cefoxitin sodium, ceftazidime, and penicillin G sodium in prefilled drug reservoirs that were stored at -20 degrees C for 30 days, thawed at 5 degrees C for four days, and pumped at 37 degrees C for one day was studied. Each antimicrobial agent was diluted with sterile water for injection to a concentration representative of the most common dosage when administered via a portable infusion pump. Ten milliliters of each drug solution was placed in individual glass vials to serve as controls, and volumes appropriate to deliver the designated dosages were loaded into the drug reservoirs. Triplicate reservoirs were prepared for each drug. One-milliliter samples from all containers were taken on days 0, 30, 31, 32, 33, 34, 34.5, and 35. All solutions were observed for color change and precipitation. Drug concentrations were determined using high-performance liquid chromatography. Leaching of the plasticizer diethylhexyl phthalate (DEHP) was analyzed by packed-column gas chromatography on days 0 and 35. No color change or precipitation was observed. No DEHP concentrations above 1 ppm were detected. More than 90% of the initial concentrations of each drug remained, except penicillin G sodium, which had a mean concentration of 83.9 +/- 0.5% at the end of the study. Cefazolin sodium, cefoxitin sodium, and ceftazidime in admixtures with sterile water for injection are stable under the conditions of this study. Penicillin G sodium should not be administered for more than 12 hours after such a cycle of freezing and thawing.     

Stability of mitomycin admixtures

The stability of mitomycin in admixtures for continuous intravenous infusion was studied. Mitomycin was reconstituted and diluted to 50 micrograms/mL in polyvinyl chloride minibags containing 5% dextrose injection 50 mL or 0.9% sodium chloride injection 50 mL. Additional mitomycin admixtures were reconstituted with a buffer solution containing monobasic and dibasic sodium phosphate; these were diluted with 5% dextrose injection only. Admixtures were stored at room temperature (27-30 degrees C) and refrigerated temperature (5 degrees C) for 120 days. Mitomycin concentrations in each admixture were tested by high-performance liquid chromatography (HPLC) immediately after admixture and at intervals during storage. Ultraviolet spectra were determined at the same time as HPLC analysis, and the admixtures were visually inspected and tested for pH. Mitomycin concentrations decreased rapidly in the unbuffered admixtures; after 12 hours at room temperature, less than 26% of the drug remained in the dextrose admixture. When the unbuffered admixtures were refrigerated for 12 hours, the mitomycin concentrations decreased 10% in the sodium chloride admixtures and 33% in the dextrose admixtures; after 24 hours, the percentages of drug loss were 23% and 42%, respectively. Mitomycin concentrations in the buffered admixtures showed no substantial decrease during 120 days at 5 degrees C. At room temperature, concentrations decreased 10% after 15 days. When the admixture is buffered to a pH of approximately 7.8, mitomycin is stable in 5% dextrose injection for up to 15 days at room temperature and at least 120 days at 5 degrees C. Unbuffered mitomycin admixtures should not be stored or administered by prolonged i.v. infusion.     

Stability of nizatidine in total nutrient admixtures.

The stability of nizatidine in total nutrient admixtures (TNAs) and the effect of the drug on the stability of lipid emulsions in the TNAs were studied. Duplicate 1476-mL amino acid-dextrose base solutions were prepared; nizatidine 300 mg was added to one. TNAs were prepared by adding to 75-mL samples of the base solutions Intralipid (KabiVitrum) or Liposyn II (Abbott) and sterile water as needed to achieve final lipid concentrations of 3% and 5%. Triplicate 100-mL samples for each lipid product and concentration were prepared; fat-free samples containing nizatidine were also studied. The theoretical final nizatidine concentration was 150 micrograms/mL. Samples were stored at 22 degrees C for 48 hours. Initially and at 12, 24, and 48 hours, the samples were visually inspected, tested for pH and particle-size distribution, and assayed by high-performance liquid chromatography for nizatidine concentration. No color change, precipitation, creaming, or oiling out was noted. For the 12 TNAs containing nizatidine, mean solution pH during the study was 5.88; stability of the lipid products requires pH values greater than or equal to 5.5. Particle-size distribution did not differ appreciably between the nizatidine-containing and drug-free TNAs. Nizatidine concentrations remained greater than 90% of the initial concentration. Nizatidine at a theoretical concentration of 150 micrograms/mL was stable for 48 hours at 22 degrees C in TNA solutions containing 3% and 5% Intralipid or Liposyn II and did not appear to affect lipid emulsion stability.     

Stability of fluorouracil administered through four portable infusion pumps

The stability of fluorouracil in four portable infusion pumps under simulated infusion conditions was studied. Three commercially available fluorouracil aqueous solutions (50 mg/mL) were used. Samples adjusted to six pH levels were examined for precipitate. Drug reservoirs of four different portable infusion pumps were filled with 70 mL of each fluorouracil injection. Under conditions simulating actual use, the reservoirs were attached to the pumps and the solutions were pumped at a rate of 10 mL/24 hours over a seven-day period at 25 degrees C and 37 degrees C. Samples at the distal end of the extension tubing were collected hourly for the first 10 hours and at 12-hour intervals thereafter. Visual observations and pH determinations were made immediately. Drug concentrations were determined by reverse-phase high-performance liquid chromatography. Diethylhexylphthalate (DEHP) concentrations (the result of leaching from the plastic tubing and container) were determined by gas chromatography. In the pH study, precipitate appeared immediately in all fluorouracil injections below pH 8.52; precipitate was observed after two to four hours at pH 8.60-8.68. Under simulated infusion conditions, no apparent changes in concentration or pH were detected with any of the brands of drugs or portable infusion devices. At 25 degrees C, a fine white precipitate was observed in the extension tubing of all devices with the Roche brand of fluorouracil 48 to 96 hours after the pumping cycle began. The amount of DEHP leached from the drug reservoirs over the seven-day period was less than 1 ppm at both temperatures. All tested brands of fluorouracil injection were found to be stable under simulated infusion conditions over a seven-day period at 37 degrees C.     

Gas production of three brands of ceftazidime

Two sodium carbonate formulations of ceftazidime (Tazidime and Tazicef) and a new arginine formulation (Ceptaz) were evaluated for gas production and bubble formation within the drug reservoir and extension tubing of a portable infusion pump during a 24-hour delivery cycle. Triplicate samples of each brand of ceftazidime were studied under identical conditions. All formulations were constituted and diluted with sterile water for injection to a concentration of approximately 33 mg/mL, drawn into syringes, and expelled into infusion-pump drug reservoirs. Triplicate samples of degassed Tazidime and Tazicef were evaluated in the same manner. In one set of triplicate experiments, reservoirs for each formulation were attached to portable infusion pumps immediately after filling at room (23 degrees C) temperature and were programmed to deliver 25 mL over one hour every eight hours for a 24-hour delivery cycle. In a second experiment, reservoirs containing triplicate samples of each product were refrigerated (3 degrees C) for 24 hours before they were attached to the pumps for dose delivery. Visual observations were made for all pumping devices. In addition, multiple vials of each formulation were constituted, and the headspace pressure of the various formulations was monitored to compare the pressure build-up due to carbon dioxide. The presence of carbon dioxide was confirmed by gas chromatography. Pressure build-up due to carbon dioxide formation occurred in the ceftazidime sodium carbonate vials only. The sodium carbonate formulations required degrassing to reduce gas and bubble formation to a manageable level after constitution. Additionally, drug was lost because of spewing of some samples during withdrawal from the vial.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of nizatidine in commonly used intravenous fluids and containers

The stability of nizatidine in commonly used i.v. fluids stored in glass and plastic containers was studied. Stock solutions of nizatidine 0.75, 1.5, and 3.0 mg/mL in 15 i.v. fluids were prepared using nizatidine injection 25 mg/mL. Six 50-mL aliquots of each solution were transferred to separate glass infusion bottles and stored at room temperature or under refrigeration. Twenty-one 40-mL aliquots of additional stock solutions of nizatidine 0.75 and 3.0 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were transferred to polyvinyl chloride (PVC) bags and stored at room or refrigerated temperature; some of these solutions were frozen, thawed, and refrigerated before analysis. Samples of each admixture were analyzed after 0.5, 1, 2, 3, and 7 days of storage for nizatidine concentration using a stability-indicating high-performance liquid chromatographic assay and also for visible changes and pH. The concentration of nizatidine in each admixture remained within 92%-106% of actual initial storage concentration throughout the study period, with the exception of nizatidine 3.0 mg/mL in 8.5% amino acid injection. The stability of nizatidine in admixtures stored in polyvinyl chloride bags was similar to that of admixtures stored in glass bottles. In the i.v. fluids, concentrations, and containers studied, nizatidine admixtures are stable for at least 7 days at either room or refrigerated temperature and 30 days when stored frozen in polyvinyl chloride bags. Admixtures of nizatidine 3.0 mg/mL in 8.5% amino acid injection should not be stored at room temperature for longer than four days.