Stability of ranitidine hydrochloride at dilute concentration in intravenous infusion fluids at room temperature

The stability of ranitidine at low concentration (0.05 mg/mL) in five intravenous infusion solutions (0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose with 0.45% sodium chloride, and 5% dextrose with lactated Ringer's injections) was studied. Admixtures were stored for seven days at room temperature in 150-mL and 1-L polyvinyl chloride infusion bags. Ranitidine stability in 0.9% sodium chloride injection and in 5% dextrose injection was also examined for up to 28 days, and these data were compared with data obtained at higher ranitidine concentrations (0.5-2.0 mg/mL). At intervals during the storage periods, color, clarity, and solution pH were examined and ranitidine content was determined by a stability-indicating high-performance liquid chromatographic assay. Ranitidine content remained greater than 90% of the initial concentration for more than 48 hours in all infusion fluids except 5% dextrose with lactated Ringer's injection. No visual changes or appreciable changes in pH were observed for any of the solutions. At the dilute concentration, ranitidine was markedly more stable after eight hours in 0.9% sodium chloride injection than in 5% dextrose injection. In 0.9% sodium chloride injection, ranitidine concentrations remained above 95% for up to 28 days, but drug concentrations in 5% dextrose injection fell below 90% after seven days. Stability in 5% dextrose injection improved as ranitidine concentrations increased from 0.05 to 2.0 mg/mL. Ranitidine (0.05 mg/mL) is stable for at least 48 hours at room temperature in all infusion fluids tested except 5% dextrose with lactated Ringer's injection.     

Compatibility of ondansetron hydrochloride and methylprednisolone sodium succinate in multilayer polyolefin containers.

PURPOSE: The compatibility of ondansetron hydrochloride and methylprednisolone sodium succinate in 5% dextrose injection and 0.9% sodium chloride injection was studied. METHODS: Test solutions of ondansetron hydrochloride 0.16 mg/mL and methylprednisolone sodium succinate 2.4 mg/mL were prepared in triplicate and tested in duplicate. Total volumes of 4 and 2 mL of ondansetron hydrochloride solution and methylprednisolone sodium succinate solution, respectively, were added to 50-mL multilayer polyolefin bags containing 5% dextrose injection or 0.9% sodium chloride injection. Bags were stored for 24 hours at 20-25 degrees C and for 48 hours at 4-8 degrees C. Chemical compatibility was measured with high-performance liquid chromatography, and physical compatibility was determined visually. RESULTS: Ondansetron hydrochloride was stable for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C. Methylprednisolone sodium succinate was stable for up to 48 hours at 4-8 degrees C. When stored at 20-25 degrees C, methylprednisolone sodium succinate was stable for up to 7 hours in 5% dextrose injection and up to 24 hours in 0.9% sodium chloride injection. Compatibility data for solutions containing ondansetron hydrochloride plus methylprednisolone sodium succinate revealed that each drug was stable for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C. CONCLUSION: Ondansetron 0.16 mg/mL (as the hydrochloride) and methylprednisolone 2.4 mg/mL (as the sodium succinate) mixed in 50-mL multilayer polyolefin bags were stable in both 5% dextrose injection and 0.9% sodium chloride injection for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C.     

Physical and chemical stability of gemcitabine hydrochloride solutions.

OBJECTIVE: To evaluate the physical and chemical stability of gemcitabine hydrochloride (Gemzar-Eli Lilly and Company) solutions in a variety of solution concentrations, packaging, and storage conditions. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Test conditions included (1) reconstituted gemcitabine at a concentration of 38 mg/mL as the hydrochloride salt in 0.9% sodium chloride or sterile water for injection in the original 200 mg and 1 gram vials; (2) reconstituted gemcitabine 38 mg/mL as the hydrochloride salt in 0.9% sodium chloride injection packaged in plastic syringes; (3) diluted gemcitabine at concentrations of 0.1 and 10 mg/mL as the hydrochloride salt in polyvinyl chloride (PVC) minibags of 0.9% sodium chloride injection and 5% dextrose injection; and (4) gemcitabine 0.1, 10, and 38 mg/mL as the hydrochloride salt in 5% dextrose in water and 0.9% sodium chloride injection as simulated ambulatory infusions at 32 degrees C. Test samples of gemcitabine hydrochloride were prepared in the concentrations, solutions, and packaging required. MAIN OUTCOME MEASURES: Physical and chemical stability based on drug concentrations initially and after 1, 3, and 7 days of storage at 32 degrees C and after 1, 7, 14, 21, and 35 days of storage at 4 degrees C and 23 degrees C. RESULTS: The reconstituted solutions at a gemcitabine concentration of 38 mg/mL as the hydrochloride salt in the original vials occasionally exhibited large crystal formation when stored at 4 degrees C for 14 days or more. These crystals did not redissolve upon warming to room temperature. All other samples were physically stable throughout the study. Little or no change in particulate burden or the presence of haze were found. Gemcitabine as the hydrochloride salt in the solutions tested was found to be chemically stable at all concentrations and temperatures tested that did not exhibit crystallization. Little or no loss of gemcitabine occurred in any of the samples throughout the entire study period. However, refrigerated vials that developed crystals also exhibited losses of 20% to 35% in gemcitabine content. Exposure to or protection from light did not alter the stability of gemcitabine as the hydrochloride salt in the solutions tested. CONCLUSION: Reconstituted gemcitabine as the hydrochloride salt in the original vials is chemically stable at room temperature for 35 days but may develop crystals when stored at 4 degrees C. The crystals do not redissolve upon warming. Gemcitabine prepared as intravenous admixtures of 0.1 and 10 mg/mL as the hydrochloride salt in 5% dextrose injection and 0.9% sodium chloride injection in PVC bags and as a solution of 38 mg/mL in 0.9% sodium chloride injection packaged in plastic syringes is physically and chemically stable for at least 35 days at 4 degrees C and 23 degrees C. Gemcitabine as the hydrochloride salt is stable for at least 7 days at concentrations of 0.1, 10, and 38 mg/mL in 5% dextrose injection and 0.9% sodium chloride injection stored at 32 degrees C during simulated ambulatory infusion.     

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 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.     

Interaction of aztreonam with nafcillin in intravenous admixtures

An interaction between aztreonam and nafcillin sodium in 0.9% sodium chloride injection or 5% dextrose injection stored in glass or plastic containers is reported. During preliminary experiments, admixtures of aztreonam 10 or 20 mg/mL and nafcillin sodium 10 or 20 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection prepared in glass flasks became cloudy and showed evidence of a fine precipitate. Drug concentrations were measured with a stability-indicating high-performance liquid chromatographic (HPLC) assay. Admixtures of aztreonam 20 mg/mL and nafcillin sodium 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection were prepared in polyvinyl chloride bags and stored at room temperature (23-25 degrees C) for 48 hours. The admixtures were assayed at 0, 24, and 48 hours with the same HPLC procedure used during the pretesting experiments. The precipitates were isolated, washed, and centrifuged; the supernatant was analyzed by HPLC assay, and the final residue was analyzed by nuclear magnetic resonance (NMR) spectroscopy. The initial recoveries of drug from the pretesting experiments ranged from 99.2 to 102.4%. Analysis of the precipitates indicated that the precipitate was neither a salt nor a complex formed by the physical interaction of aztreonam and nafcillin sodium, but probably a high-molecular-weight polymer formed by the covalent bonding of subunits of the formulation components. Substantial losses of both drugs from the admixtures were evident after 48 hours of storage. The precipitate was observed sooner in the admixtures containing 0.9% sodium chloride injection than in the admixtures prepared in 5% dextrose injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

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 concentrated trimethoprim-sulfamethoxazole admixtures

The stability of trimethoprim-sulfamethoxazole (TMP-SMX) at various concentrations in 5% dextrose injection or 0.9% sodium chloride injection was studied. Appropriate volumes of TMP-SMX formulation (80 mg TMP and 400 mg SMX/5 mL) were mixed with 5% dextrose injection or 0.9% sodium chloride injection to provide dilutions of 1:25 v/v, 1:20 v/v, 1:15 v/v, and 1:10 v/v. Aliquots were removed at 0, 0.5, 1, 2, 4, 8, 14, 24, and 48 hours and filtered. The pH of the samples was determined, and the samples were assayed for trimethoprim and sulfamethoxazole content by high-performance liquid chromatography. Admixtures were visually inspected for precipitate before each sample was removed. The concentration of SMX in all admixtures did not change during the study period. The stability of TMP was dependent on concentration and vehicle. At a 1:25 v/v dilution, TMP was stable for 48 hours in 5% dextrose injection and 0.9% sodium chloride injection. At a 1:20 v/v dilution, TMP was stable for 24 hours in 5% dextrose injection and 14 hours in 0.9% sodium chloride injection. At a 1:15 v/v dilution, TMP was stable for four hours in 5% dextrose injection and two hours in 0.9% sodium chloride injection. At a 1:10 v/v dilution, TMP was stable for one hour in 5% dextrose injection and 0.9% sodium chloride injection. Concentrated solutions of TMP-SMX should be prepared in 5% dextrose injection, infused within one hour of preparation, and visually inspected for precipitation before and during infusion.     

Stability of pibenzimol hydrochloride in commonly used infusion solutions and after filtration

The stability of pibenzimol hydrochloride was evaluated after reconstitution, after addition to several intravenous fluids, and after filtration. Vials containing pibenzimol hydrochloride 50 mg were reconstituted with 2.5 mL of 0.9% sodium chloride injection to 20 mg/mL. For determination of drug stability in intravenous fluids, vial contents were further diluted to 0.15 mg/mL by injection into glass containers and polyvinyl chloride (PVC) bags containing 250 mL of 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection. Pibenzimol concentrations were determined immediately after preparation and at various intervals after storage at 4-6 degrees C or 25 degrees C by means of a stability-indicating, high-performance liquid chromatographic technique. Vial contents were inspected visually for color changes, and pH was measured. Determinations were also made of the stability of pibenzimol 0.15 mg/mL in 0.9% sodium chloride injection after simulated infusions using a 0.22-micron filter set at 25 degrees C. All study solutions and admixtures retained more than 90% of the initial pibenzimol concentration. The greatest loss of drug (6-7%) occurred after 24 hours in lactated Ringer's injection in both glass and PVC containers and in 0.9% sodium chloride injection in PVC bags. No drug loss occurred as a result of filtration. Reconstituted pibenzimol hydrochloride and admixtures of pibenzimol in 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection in glass or PVC containers are stable for at least 24 hours at 25 degrees C. Filtration has no effect on stability.     

Stability and sorption of calcitriol in plastic tuberculin syringes.

The stability of commercially formulated calcitriol 1 and 2 micrograms/mL and calcitriol formulation subsequently diluted to 0.5 microgram/mL in 0.9% sodium chloride injection, 5% dextrose injection, or water for injection was evaluated after eight hours' storage in polypropylene syringes. The apparent affinities of calcitriol for polypropylene and polyvinyl chloride were also examined. Three calcitriol 0.5 microgram/mL solutions (diluted in 0.9% sodium chloride injection, 5% dextrose injection, or water for injection) and aqueous calcitriol formulations, 1 and 2 micrograms/mL, were placed in 1-mL polypropylene tuberculin syringes and assayed by high-performance liquid chromatography initially and after two, four, and eight hours' storage under room light at ambient temperature. Samples of calcitriol 2 micrograms/mL were also exposed to polypropylene or polyvinyl chloride at room temperature for 20 days. The remaining calcitriol concentrations were determined and apparent calcitriol polymer/water partition coefficients were calculated. Calcitriol concentrations did not change substantially during the eight-hour stability study. The mean apparent polymer/water partition coefficient for polyvinyl chloride was 66 times that for polypropylene, indicating that calcitriol has a definite affinity for polyvinyl chloride but no similar affinity for polypropylene. Aqueous calcitriol solution 1 or 2 micrograms/mL or 0.5 microgram/mL in 0.9% sodium chloride injection, 5% dextrose injection, or water for injection, when stored in polypropylene syringes exposed to ambient temperature and room light, appears to be stable for eight hours. Calcitriol appears to have greater affinity for polyvinyl chloride than for polypropylene.     

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 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 and compatibility of topotecan hydrochloride with selected drugs.

The physical and chemical compatibility of topotecan 56 microg/mL (as the hydrochloride) with 18 other drugs during simulated Y-site injection was studied. A vial of topotecan hydrochloride was reconstituted under aseptic conditions with sterile water for injection to yield a solution containing 1 mg of topotecan base per milliliter and further mixed with 0.9% sodium chloride injection or 5% dextrose injection. Equal volumes of topotecan solution and each secondary drug, also prepared in 0.9% sodium chloride injection or 5% dextrose injection, were mixed in sterile vials. All mixtures were stored at 20-23 degrees C under normal fluorescent light. Samples were taken initially and at four hours for analysis by high-performance liquid chromatography, visual inspection, and pH measurement. With a few exceptions, the drug combinations exhibited no visible change in color or clarity initially or after four hours, and the concentration of topotecan hydrochloride and of the secondary drugs was 95% or more of the initial concentration. The concentration of topotecan hydrochloride dropped to 88.7% of the initial concentration after four hours when the drug was mixed with ticarcillin disodium and with clavulanate potassium in 5% dextrose injection. An intense yellow color and a slight haze developed immediately after topotecan hydrochloride was mixed with dexamethasone sodium phosphate or with fluorouracil in 0.9% sodium chloride injection. The topotecan-mitomycin combination in both diluents became pale purple immediately and turned dark pink-lavender within four hours, after which analysis showed 15-20% degradation of mitomycin. During simulated Y-site injection, topotecan hydrochloride was physically and chemically compatible with 15 of 18 drug products.     

Effect of primary fluids and dilutional volumes on the delivery of cefazolin sodium by a membrane infusion device

The influence of primary fluids and dilutional volumes on the accuracy of in vitro delivery of cefazolin sodium by gravity flow through a new controlled-release membrane infusion device was studied. For primary fluid studies, cefazolin 1 g (as the sodium salt) in 10 mL of sterile water for injection was injected into the drug chamber, which is separated by a membrane from the fluid chamber; the entire dose passes into the fluid chamber over a set time. The inlet port of the fluid chamber was connected to the 1-L primary fluid bag, and the outlet port was connected to an administration set. The primary fluids included 0.9% sodium chloride injection; 5% dextrose injection; 10% dextrose injection; 5% dextrose and 0.45% sodium chloride injection; 5% dextrose, 0.45% sodium chloride, and potassium chloride 20 meq/L injection; and 2.2% amino acids with electrolytes in 25% dextrose injection. For dilutional volume studies, cefazolin sodium 1 g diluted in 5, 10, and 15 mL of sterile water for injection was infused with 0.9% sodium chloride injection. The flow rate was set at 1 mL/min. Serial samples were collected in triplicate every five minutes over a 90-minute period and analyzed by high-performance liquid chromatography. The time needed to deliver more than 95% of the cefazolin doses ranged from 35 to 50 minutes using various primary fluids and from 35 to 55 minutes using various dilutional volumes. The manufacturer recommends that a cefazolin dose be delivered completely within 30-60 minutes. The solutes in the primary fluids and the volume injected did not appear to affect the delivery of cefazolin by a controlled-release membrane device.     

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.     

Effect of vehicle ionic strength on sorption of nitroglycerin to a polyvinyl chloride administration set

The nitroglycerin sorptive properties of a polyvinyl chloride i.v. administration set were studied, and the role played by the admixture vehicle in this process was explored. Admixtures of nitroglycerin 0.4 mg/mL were prepared in sterile water for injection, 5% dextrose injection, Ringer's injection, and 0.25%, 0.9%, and 5% sodium chloride injection. Each admixture was divided into two 500-mL sterile glass containers, and flow through the administration set at 100 mL/hr was begun. Samples of effluent were collected at intervals beginning 10 minutes after the start of the infusion and ending at 180 minutes. Nitroglycerin depletion from solution and uptake by the set was determined by an ultraviolet spectrophotometric assay. Initially, the degree of nitroglycerin loss to the set was greatest for dextrose admixtures, intermediate for water admixtures, and least for sodium chloride admixtures. Losses of about 40% were observed during the first 10 minutes; between 15 and 20 minutes, the stated pattern of drug sorption was reversed, with sodium chloride admixtures now showing the greatest loss of nitroglycerin. The availability of nitroglycerin was an inverse function of increasing ionic strength during the three-hour observation period. Nitroglycerin availability in admixtures in contact with a polyvinyl chloride administration set was dependent on the ionic strength of the vehicle and the time points in the infusion period at which measurements were made.     

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.     

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.     

Stability of ondansetron hydrochloride in injectable solutions at -20, 5, and 25 degrees C.

The stability of ondansetron hydrochloride in 5% dextrose injection and in 0.9% sodium chloride injection when stored frozen, refrigerated, and at room temperature was studied. Solutions of ondansetron 0.03 and 0.3 mg/mL (as the hydrochloride salt) were prepared by adding 1.5 or 15 mg of the drug to 50-mL minibags containing 5% dextrose injection or 0.9% sodium chloride injection. All solutions were prepared in triplicate, and each container was tested in duplicate. Testing at the time of preparation and at each subsequent test interval included visual inspection of color and clarity, determination of pH, and a stability-indicating high-performance liquid chromatographic assay to measure the ondansetron concentration. Conditions assessed included storage at -20 degrees C for two weeks to three months, 5 degrees C for 7-14 days, approximately 25 degrees C for up to 48 hours, and various combinations of these conditions. The concentration of ondansetron in each solution remained above 90% of the original concentration at each observation time under all storage conditions. No changes in color or clarity were observed, and there were only minor changes in pH. Ondansetron 0.03 and 0.3 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection was stable when stored (1) for up to three months at -20 degrees C, followed by up to 14 days at 5 degrees C and by 48 hours at 25 degrees C and (2) for up to 14 days at 5 degrees C, followed by up to 48 hours at 25 degrees C.     

Interaction of heparin sodium and dopamine hydrochloride in admixtures studied by microcalorimetry

Microcalorimetry was used to investigate the interaction between dopamine hydrochloride and heparin sodium in 5% dextrose injection and in 0.9% sodium chloride injection. Heat of reaction (in microjoules) was measured by flow calorimetry for the following combinations of solutions: dopamine hydrochloride solution and heparin sodium solution prepared from powdered forms of the drugs in water; solutions of the powdered drugs in 5% dextrose injection; solutions of the powdered drugs in 0.9% sodium chloride injection; solutions prepared in 5% dextrose injection from commercial dopamine hydrochloride injection and commercial heparin sodium injection; and solutions prepared in 0.9% sodium chloride injection from the commercial drug injections. Mixing the solutions of the powdered drugs in water caused heat to be evolved, as did mixing the solutions of the powdered drugs diluted with 5% dextrose injection and the commercial injections diluted with 5% dextrose injection. The interactions of the two drugs were believed to be ionic, based on the exothermic nature of the reaction. No heat of reaction was measurable when sodium chloride was used as the diluent. Based on this preliminary investigation, admixtures containing heparin sodium and dopamine hydrochloride should be mixed in 0.9% sodium chloride injection to minimize the risk of interaction between the two drugs.