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 fentanyl citrate in 0.9% sodium chloride solution in portable infusion pumps

The stability of fentanyl citrate diluted with 0.9% sodium chloride injection for use in portable infusion pumps was studied. The commercially available injection containing 50 micrograms of fentanyl per milliliter was diluted to a concentration of 20 micrograms/mL. Twelve 100-mL portions of the dilute solution were placed in polyvinyl chloride infusion pump drug reservoirs; six were stored at 3 degrees C and six at 23 degrees C; three at each temperature were overwrapped with polypropylene-Mylar. Initially and after 5, 10, 20, and 30 days of storage, 1-mL samples were taken from each reservoir, inspected for color change and precipitation, and assayed for fentanyl concentration by high-performance liquid chromatography. Initially and on day 30, pH of the samples was checked. No precipitation or change in color or pH was observed. No substantial decrease in fentanyl concentration was found in either the wrapped or unwrapped samples at either temperature, although concentrations on day 30 in the samples at 23 degrees C were slightly lower than those at 3 degrees C. Under the conditions studied, fentanyl citrate solutions containing 20 micrograms of fentanyl per milliliter can be stored for 30 days in polyvinyl chloride reservoirs for portable infusion pumps.     

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 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 ceftazidime and amino acids in parenteral nutrient solutions

The stability of ceftazidime was studied under conditions simulating administration via a Y-injection site into a primary infusion of parenteral nutrient (PN) solution; the stabilities of ceftazidime and amino acids when the drug was added directly to PN solutions were also studied. Three PN solutions containing 25% dextrose were used; the amino acid contents were 0, 2.5%, and 5%. Ceftazidime with sodium carbonate was used to prepare stock solutions of ceftazidime 40 mg/mL in both 0.9% sodium chloride injection and 5% dextrose injection; to simulate Y-site injection, samples were added to the three PN solutions to achieve ceftazidime concentrations of 10 and 20 mg/mL, or 1:1 and 1:3 ratios of drug solution to PN solution. Samples of these admixtures were assayed by high-performance liquid chromatography (HPLC) initially and after room-temperature (22 degrees C) storage for one and two hours. Additional solutions were prepared by adding sterile water for injection to ceftazidime with sodium carbonate; drug solutions were added to each PN solution in polyvinyl chloride bags to achieve ceftazidime concentrations of 1 and 6 mg/mL. The samples were assayed by HPLC for ceftazidime concentration after storage at 22 degrees C for 3, 6, 12, 24, and 36 hours and at 4 degrees C for 1, 3, 7, and 14 days. Amino acid stability was analyzed in admixtures containing 5% amino acids and ceftazidime 6 mg/mL after 24 and 48 hours at 22 degrees C and after 7 and 10 days at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of intravenous admixtures of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin

The stability of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin in intravenous admixtures containing aztreonam and one of the other drugs was studied. Admixtures of aztreonam and gentamicin, aztreonam and tobramycin, and aztreonam and cefoxitin were each prepared in four different concentrations in both 0.9% sodium chloride injection and 5% dextrose injection. Admixtures of aztreonam and metronidazole were prepared in two different concentrations using a commercially available solution of metronidazole 5 mg/mL in a phosphate-citrate buffer. One of each of these admixtures was stored at 25 degrees C for 48 hours and at 4 degrees C for seven days. At various storage times, 1-mL samples of the admixtures were tested for pH and assayed using high-performance liquid chromatography or fluorescence polarization immunoassay. The pH of all admixtures except admixtures of aztreonam and cefoxitin decreased only slightly during storage. Concentrations of aztreonam and tobramycin under both storage conditions decreased by less than 10%. Concentrations of cefoxitin and aztreonam decreased by more than 10% at 25 degrees C, and concentrations of gentamicin decreased by more than 10% under both storage conditions. Visual inspection of admixtures of aztreonam and metronidazole revealed an incompatibility between the two drugs, as evidenced by the appearance of a cherry-red color. Admixtures of aztreonam 10 and 20 mg/mL and tobramycin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 48 hours at 25 degrees C or seven days at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and gentamicin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for eight hours at 25 degrees C and 24 hours at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and cefoxitin 10 and 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 12 hours at 25 degrees C and seven days at 4 degrees C. Aztreonam and metronidazole should be administered separately.     

Compatibility and stability of linezolid injection admixed with three cephalosporin antibiotics

OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with cefazolin sodium 1 gram, ceftazidime 2 grams, and ceftriaxone sodium 1 gram for 7 days at 4 degrees C and 23 degrees C. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: The test samples were prepared by adding the required amount of the cephalosporin antibiotic to bags of linezolid injection 200 mg/100 mL. MAIN OUTCOME MEASURES: Physical stability and chemical stability based on drug concentrations initially and after 1, 3, 5, and 7 days of storage at 4 degrees C and 23 degrees C protected from light. RESULTS: All of the linezolid admixtures with cephalosporins were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change. The cefazolin sodium-containing samples were colorless throughout the study. The admixtures with ceftazidime and ceftriaxone sodium had a slight yellow tinge initially, and the room temperature samples became a frank yellow color after 5 days. The refrigerated samples did not change color. High-performance liquid chromatography analysis found little or no loss of linezolid in any sample stored at either temperature throughout the study. Cefazolin sodium and ceftazidime in the linezolid admixtures at 4 degrees C remained stable for 7 days, but at 23 degrees C cefazolin sodium was stable for 3 days and ceftazidime for only 24 hours before cephalosporin decomposition exceeded 10%. Ceftriaxone sodium was less stable in the admixtures; 10% loss occurred in 3 days at 4 degrees C and more than 20% loss occurred in 24 hours at 23 degrees C. CONCLUSION: Admixtures of linezolid 200 mg/100 mL with cefazolin sodium 1 gram and ceftazidime 2 grams were physically compatible and chemically stable for at least 7 days stored at 4 degrees C protected from light and for 3 days and 1 day, respectively, at 23 degrees C protected from light. Admixtures of linezolid with ceftriaxone sodium 1 gram exhibited a rapid rate of cephalosporin loss at 23 degrees C, which precludes admixture of the two drugs.     

Stability of three cephalosporin antibiotics in AutoDose Infusion System bags

OBJECTIVE: To evaluate the physical and chemical stability of three commonly used cephalosporin antibiotic solutions packaged in AutoDose Infusion System bags stored and evaluated at appropriate intervals for up to 7 days at 23 degrees C and up to 30 days at 4 degrees C. SETTING: Laboratory. INTERVENTIONS: The test samples were prepared by adding the required amount of the cephalosporin antibiotic to the AutoDose Infusion System bags and diluting to the target concentration with 0.9% sodium chloride injection. MAIN OUTCOME MEASURES: Physical stability and chemical stability based on drug concentrations initially and at appropriate intervals over periods of up to 7 days at 23 degrees C and up to 30 days at 4 degrees C. RESULTS: All of the cephalosporin admixtures were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change. The cefazolin sodium-containing samples were colorless throughout the study. The admixtures with ceftazidime and ceftriaxone sodium had a slight yellow tinge initially, and the room temperature samples turned a frank yellow color after 5 days. The refrigerated samples did not change color. High-performance liquid chromatography analysis showed that cefazolin sodium and ceftriaxone sodium remained stable for 30 days and ceftazidime remained stable for 7 days at 4 degrees C. At room temperature, losses were much more rapid. Cefazolin sodium and ceftriaxone sodium retained at least 90% of their initial concentrations through 7 days and 5 days, respectively, when stored at 23 degrees C. Ceftazidime remained stable for only 1 day at 23 degrees C. CONCLUSION: Cefazolin sodium, ceftazidime, and ceftriaxone sodium exhibited physical and chemical stabilities consistent with those found in previous studies of these drugs. The AutoDose Infusion System bags did not adversely affect the physical and chemical stabilities of these three cephalosporin antibiotics.     

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 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.     

Compatibility of cefoperazone sodium and furosemide in 5% dextrose injection

The compatibility of cefoperazone sodium and furosemide in 5% dextrose injection stored at two temperatures was studied. Cefoperazone sodium and furosemide were added to 5% dextrose injection to achieve a cefoperazone concentration of 10 mg/mL and a furosemide concentration of 0.2 mg/mL. The admixture was stored in 100-mL vented i.v. containers in the dark under refrigeration (4 degrees C) and at room temperature (25 degrees C); three containers were stored at each temperature. A 1-mL sample was taken from each i.v. container immediately after preparation and after 1, 2, 5, 10, 15, 20, and 25 days to be inspected visually, checked for pH value, and analyzed by a stability-indicating high-performance liquid chromatographic method. No color change or precipitation was observed in any sample at any time during the study. More than 95% of the initial concentrations of both drugs remained for five days at 4 degrees C but for only two days at 25 degrees C. Cefoperazone sodium was somewhat more stable than furosemide under the same storage conditions for 25 days; however, less than a 2% difference between the drugs was noted. Under the conditions of this study, cefoperazone sodium 10 mg/mL and furosemide 0.2 mg/mL in admixtures in 5% dextrose injection are stable for only two days at 25 degrees C and five days at 4 degrees C.     

Stability of ceftazidime in plastic syringes and glass vials under various storage conditions.

The stability of ceftazidime solutions (100 and 200 mg/mL) in plastic syringes and glass vials under various storage conditions was examined. Solutions of ceftazidime 100 and 200 mg/mL in sterile water were placed in polypropylene plastic syringes or glass vials and stored (1) at 21-23 degrees C for up to 8 hours, (2) at 4 degrees C for up to 96 hours, (3) at -20 degrees C for 28 days and then 21-23 degrees C for up to 8 hours, (4) at -20 degrees C for 28 days and then 4 degrees C for up to 96 hours, (5) at -20 degrees C for 91 days and then 21-23 degrees C for up to 8 hours, or (6) at-20 degrees C for 91 days and then 4 degrees C for up to 96 hours. Samples were withdrawn from each syringe and vial at designated times and assayed by high-performance liquid chromatography. Solutions were judged to be stable if drug concentrations remained above 90% of the initial values. The number of particles in each container under each storage condition was also evaluated. Ceftazidime was stable under all storage conditions. In all containers, particulate matter was within USP specifications for small-volume injections, with no change in particle count as a result of the freezing and thawing. Ceftazidime in sterile water in either glass vials or plastic syringes is stable for 8 hours at room temperature or 96 hours at 4 degrees C when such storage occurs (1) immediately after constitution, (2) after 28 days of frozen storage, or (3) after 91 days of frozen storage.     

Stability of ceftazidime (with arginine) stored in plastic syringes at three temperatures.

The stability of ceftazidime (with arginine) stored in plastic syringes at three temperatures was studied. Ceftazidime (with arginine) was reconstituted with sterile water for injection to a concentration of 100 mg/mL and transferred to plastic syringes. Syringes were stored at 22 degrees C for 24 hours; at 4 degrees C for 7 or 10 days, then at 22 degrees C for 24 hours; or at -20 degrees C for 91 days, then at 22 degrees C for 24 hours or at 4 degrees C for seven days followed by 22 degrees C for 24 hours. Ceftazidime concentration was measured at various times by using a stability-indicating high-performance liquid chromatographic method. At each sampling time, each syringe was visually inspected and the pH of each solution was measured. Mean ceftazidime concentration remained > 90% of initial concentration at all storage conditions. Although during storage the color of the solutions changed from light straw to dark yellow and the pH decreased, no precipitate was visually detected and no peaks for degradation products appeared on the chromatograms. Ceftazidime 100 mg/mL (with arginine) in sterile water for injection was stable when stored in plastic syringes for up to 24 hours at 22 degrees C, for 10 days at 4 degrees C followed by up to 24 hours at 22 degrees C, and for 91 days at -20 degrees C followed by up to 24 hours at 22 degrees C or by 7 days at 4 degrees C and up to 24 hours at 22 degrees C.     

Stability of methylprednisolone sodium succinate in autodose infusion system bags

OBJECTIVE: To evaluate the physical and chemical stabilities of methylprednisolone sodium succinate solutions packaged in sterile AutoDose Infusion System bags. SETTING: Laboratory. INTERVENTIONS: The test samples were prepared by reconstituting the methylprednisolone sodium succinate, adding the required amount of drug to the AutoDose Infusion System bags, and diluting to the target concentrations of 100 mg/100 mL and 1 gram/100 mL with 0.9% Sodium Chloride Injection. MAIN OUTCOME MEASURES: Physical stability and chemical stability based on drug concentrations initially and at appropriate intervals over periods up to 3 days at 23 degrees C and 30 days at 4 degrees C. RESULTS: The admixtures initially were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and exhibited little change. All samples were essentially colorless throughout the study. High-performance liquid chromatography analysis revealed some decomposition in the samples. Methylprednisolone sodium succinate exhibited about 8% loss after 2 days and about 13% loss after 3 days at 23 degrees C. In the samples stored at 4 degrees C, methylprednisolone sodium succinate exhibited acceptable stability through 21 days of storage, but losses exceeded 10% after 30 days. CONCLUSION: Methylprednisolone sodium succinate exhibited physical and chemical stabilities consistent with those found in previous studies. The AutoDose Infusion System bags did not adversely affect the physical or chemical stability of this drug.     

Stability of aqueous solutions of amoxicillin sodium in the frozen and liquid states

The stability of aqueous admixtures of amoxicillin sodium in both the liquid and frozen (solid) states was studied. Admixtures of amoxicillin sodium were prepared in sterile water for injection to a theoretical concentration of 10 mg/mL. For each experimental run, 2-mL aliquots of the admixture were placed in stoppered glass volumetric flasks and stored at temperatures ranging from 19.5 degrees C to -30 degrees C; 16 flasks were stored at each temperature. After equilibration for approximately 20 minutes, duplicate flasks at each temperature were removed from storage conditions for time-zero assay. Subsequently, duplicate flasks were assayed at various times, depending on the storage temperature, for up to 13 days or until more than 80% of the drug had degraded. All samples were assayed at least in duplicate using high-performance liquid chromatography. When amoxicillin solutions were in the liquid state (at temperatures between 19.5 and 0 degrees C), the time required for the amoxicillin concentration to decrease to 90% of its initial value (t90) increased as temperature decreased. However, between 0 degree C and -7 degrees C, the t90 of frozen solutions decreased from two days to 1.08 hours. As temperature declined further, the rate of degradation decreased until the solution was completely frozen; at -30 degrees C, the t90 had increased to 13 days. Amoxicillin sodium is unstable in aqueous solutions stored between 0 degrees C and -20 degrees C. If admixtures of this drug are to be frozen for later use, the storage temperature should be below -30 degrees C.     

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 cefonicid sodium in infusion fluids

The chemical stability of cefonicid sodium in infusion fluids was analyzed. Cefonicid sodium vials were reconstituted and diluted with sterile water for injection and other commonly used intravenous fluids to concentrations of 325, 220, 40, 20, and 5 mg/mL. Cefonicid concentration was analyzed by high-performance liquid chromatography initially and after storage at room temperature and 5 degrees C. Reconstituted vials were frozen as long as eight weeks, thawed, and kept at room temperature and 5 degrees C and then analyzed. Cefonicid sodium reconstituted in each of the diluents studied exhibited no change in clarity and very little change in potency after 24 hours at room temperature and after 72 hours at 5 degrees C. Some vials with high concentrations became turbid between 72 and 96 hours at 5 degrees C. The thawed vials were chemically stable for 24 hours at room temperature and for 96 hours at 5 degrees C. When reconstituted with sterile water for injection and other commonly used intravenous fluids, cefonicid sodium vials and small-volume infusions are chemically stable for 24 hours at room temperature and for 72 hours at 5 degrees C. Reconstituted cefonicid sodium vials can be frozen and stored for as long as eight weeks, thawed, and then kept at room temperature for 24 hours or at 5 degrees C for 72 hours.     

Stability of ranitidine in intravenous admixtures stored frozen, refrigerated, and at room temperature

The stability of ranitidine in concentrations of 0.5, 1.0, and 2.0 mg/mL in admixtures with commonly used i.v. fluids was studied. The admixture vehicles were 0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose and 0.45% sodium chloride, and 5% dextrose with lactated Ringer's (DLR) injections in polyvinyl chloride bags. Three bags were prepared for each test solution and stored under each of the following conditions: seven days at room temperature (23 +/- 1 degrees C) in normal laboratory lighting, 30 days at 4 degrees C, and 60 days at -20 degrees C followed by either seven days at room temperature (in light) or 14 days at 4 degrees C. Ranitidine content was determined by high-performance liquid chromatography at several intervals. Color, clarity, and pH were also examined. Ranitidine concentrations remained greater than or equal to 90% of initial concentrations under all storage conditions except in the frozen DLR admixtures. Drug loss in the DLR admixtures was greatest at the lower ranitidine concentrations. The only visual changes were yellow color in the thawed DLR admixtures and those containing ranitidine 2.0 mg/mL in 5% dextrose and 0.45% sodium chloride. Slight increases in the pH of some admixtures were noted. Ranitidine is stable for seven days at room temperature and 30 days at 4 degrees C at all concentrations and in all vehicles studied. At the studied concentrations, the drug is stable in admixtures frozen for 60 days and stored for seven days at room temperature or 14 days refrigerated, except in DLR admixtures; these admixtures should not be stored frozen.     

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.     

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)