Stability and preservative effectiveness of treprostinil sodium after dilution in common intravenous diluents.

The stability of treprostinil sodium after dilution in three common i.v. infusion vehicles was assessed. The chemical stability of treprostinil sodium was tested over a 48-hour period at 40 degrees C and 75% relative humidity after dilution in each of three diluents: sterile water for injection, 0.9% sodium chloride injection, and 5% dextrose injection, and after passage through an i.v. delivery system. Chemical analysis was conducted by using a validated stability-indicating high-performance liquid chromatographic assay, visually inspecting the solutions, and measuring the pH of each solution. The preservative effectiveness of the solutions was tested by the recovery of inoculations of compendial microorganisms after 48 hours in dilute solutions of treprostinil sodium. All assay results for treprostinil were within 90.0% to 110.0% of the prepared solutions diluted at 0.004 and 0.13 mg/mL treprostinil sodium in sterile water for injection and 0.9% sodium chloride injection. The assay results were the same for dilute treprostinil solutions in 5% dextrose injection at concentrations of 0.02 and 0.13 mg/mL. The pH values for these solutions remained within acceptable values of 6.0 to 7.2 for the stability study. No change in physical appearance or any visible particulate matter was observed. Approximately 70% of metacresol, the preservative, in the dilute treprostinil sodium solutions was removed before reaching the terminal end of the tubing. None of the dilute treprostinil sodium solutions supported microbial growth in the cassette reservoirs for the organisms considered. Treprostinil sodium 0.13 mg/mL solution in sterile water for injection, 0.9% sodium chloride for injection, and 5% dextrose for injection appeared to be stable after storage in controlled ambulatory drug-delivery systems for 48 hours at 40 degrees C and 75% relative humidity. Treprostinil sodium 0.004 mg/mL in sterile water and 0.9% sodium chloride for injection and 0.02 mg/mL in 5% dextrose injection was also stable under the same conditions. None of the solutions showed signs of microbial growth.     

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

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

Stability of 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.     

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.     

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.     

Osmolality of small-volume i.v. admixtures for pediatric patients

The osmolalities of pediatric i.v. admixtures were measured to identify drug concentrations in selected vehicles that would conserve fluid while maintaining osmolality values of 400 mOsm/kg or less. Test solutions were prepared by diluting appropriate volumes of freshly reconstituted powdered drug products or commercially diluted drug products with 5% dextrose injection, 0.9% sodium chloride injection, or both to provide 5 mL of each admixture at desired drug concentrations. To reduce their osmolalities, trimethoprim-sulfamethoxazole and ampicillin sodium were also diluted in 0.45% sodium chloride injection; ticarcillin disodium was diluted only in 0.45% sodium chloride injection. A vapor pressure osmometer was used to measure osmolalities in triplicate for three solutions prepared for each admixture. Of the 63 different admixtures prepared with 5% dextrose injection or 0.9% sodium chloride injection or both, 47 (75%) had osmolalities of 400 mOsm/kg or less. At least one concentration of each selected drug diluted in these vehicles had an osmolality of less than 425 mOsm/kg, except for trimethoprim-sulfamethoxazole and ampicillin sodium. Selected concentrations of the latter two drugs and ticarcillin disodium in 0.45% sodium chloride injection resulted in acceptable osmolalities. For most drugs diluted to the same concentration in 5% dextrose injection and 0.9% sodium chloride injection, osmolalities were lower in the dextrose solutions. Selection of an appropriate vehicle and drug concentration can control the osmolality of i.v. admixtures when the volume of fluid must be minimized, as for pediatric patients.     

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 sorption of FK 506 in 5% dextrose injection and 0.9% sodium chloride injection in glass, polyvinyl chloride, and polyolefin containers.

The effects of the diluent, the storage container, light, and infusion through various types of tubing on the stability and sorption of FK 506 were studied. Solutions of FK 506 in 0.9% sodium chloride injection or 5% dextrose injection were stored at room temperature (24 +/- 2 degrees C) in glass i.v. bottles, polyvinyl chloride (PVC) minibags, and polyolefin containers. FK 506 solution in 0.9% sodium chloride injection was stored in plastic syringes at room temperature and either exposed to normal room light or stored in the dark. FK 506 solution in 5% dextrose injection was placed in plastic syringes and infused through PVC anesthesia extension tubing, PVC i.v. administration set tubing, and fat emulsion tubing over a two-hour period. The infused samples and samples collected from the containers and syringes at intervals up to 48 hours were analyzed for FK 506 concentration by high-performance liquid chromatography. FK 506 concentrations remained greater than 90% of initial concentration for admixtures in 5% dextrose injection stored in glass bottles for 48 hours and for admixtures in 5% dextrose injection or 0.9% sodium chloride injection stored in polyolefin containers for 48 hours. No change in concentration was measured for admixtures in 0.9% sodium chloride injection stored in plastic syringes, and exposure to light did not affect the stability of FK 506 solution. No substantial change in concentration occurred in FK 506 solution in 5% dextrose injection infused through PVC anesthesia extension tubing, PVC i.v. administration set tubing, or fat emulsion tubing. FK 506 admixtures prepared with 5% dextrose injection or 0.9% sodium chloride injection should be stored in polyolefin containers. If polyolefin containers are not available, solutions should be prepared with 5% dextrose injection and stored in glass bottles.     

Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 1: stability with common intravenous fluids.

The stability of dopamine hydrochloride (Intropin) in several large-volume parenteral solutions was studied. Admixtures of dopamine were assayed by colorimetric and chromatographic procedures. Admixtures (800 mug dopamine per ml) in the following intravenous fluids in glass bottles at pH 6.85 or below were found to be chemically and physically stable for at least 48 hours at room temperature: dextrose 5%, dextrose 5% and sodium chloride 0.9%, 5% dextrose in 0.45% sodium chloride, dextrose 5% in lactated Ringer's solution, lactated Ringer's injection, 0.9% sodium chloride, 1/6 molar sodium lactate, and 20% mannitol. The admixture of dopamine in 5% dextrose was stable for a minimum of seven days at 5 C. A 5% dextrose-dopamine admixture in a polyvinylchloride bag was stable for at least 24 hours at room temperature. The admixture of dopamine in 5% sodium bicarbonate solution produced an unstable solution of pH 8.20. A chemical and physical change (development of a pink color) was observed in this admixture. It is recommended that dopamine not be added to 5% sodium bicarbonate solution or any alkaline intravenous solution.     

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

The stability of dobutamine hydrochloride (250 micrograms/ml) and verapamil hydrochloride (160 micrograms/ml) alone and in combination in 0.9% sodium chloride injection or 5% dextrose injection was studied. Solutions were stored both in plastic i.v. bags and in amber-colored glass bottles at 24 degrees C and 5 degrees C for up to seven days. Before storage and at various times during storage, solutions were assayed at least in triplicate by high-performance liquid chromatography, pH was recorded, and visual appearance was noted. All solutions tested under all conditions retained at least 90% potency for seven days. In plastic i.v. bags, dobutamine either alone or in combination with verapamil in both diluents turned a light-pink color in 24 hours at 24 degrees C. The intensity of the pink color increased with time in 0.9% sodium chloride injection; in 5% dextrose injection, solutions, became clear in 48 hours. The pH of solutions prepared in plastic i.v. bags in 5% dextrose injection decreased from 4.0 to 3.1 during the seven-day period at 24 degrees C; results for solutions in amber bottles were similar. At 5 degrees C, the pH and clarity of all solutions in bags and bottles remained stable for seven days. At the concentrations tested, dobutamine hydrochloride combined with verapamil hydrochloride is stable in 0.9% sodium chloride injection and 5% dextrose injection for 48 hours at 24 degrees C and for seven days at 5 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 an ofloxacin injection in various infusion fluids.

The stability of ofloxacin was evaluated in 10 different infusion fluids under various storage conditions. Solutions of ofloxacin (0.4 mg/mL and 4.0 mg/mL) were prepared in (1) 0.9% sodium chloride injection; (2) 5% dextrose injection; (3) 5% dextrose and 0.9% sodium chloride injection; (4) 5% dextrose and lactated Ringer's injection; (5) 5% sodium bicarbonate injection; (6) Plasma-Lyte 56 and 5% dextrose injection; (7) 5% dextrose, 0.45% sodium chloride, and 0.15% potassium chloride injection; (8) 1/6 M sodium lactate injection; (9) water for injection; and (10) 20% mannitol injection. Each solution was injected into polyvinyl chloride bags and stored at (1) 24 degrees C for 3 days, (2) 5 degrees C for 7 days, (3) 5 degrees C for 14 days, (4) -20 degrees C for 13 weeks and then 5 degrees C for 14 days, or (5) -20 degrees C for 26 weeks and then 5 degrees C, for 14 days. Samples were assayed initially and after storage by high-performance liquid chromatography and examined for visual clarity, pH, turbidity, and particulates. Ofloxacin was stable in all solutions and under all storage conditions. All of the solutions were clear, pH was stable, and particulate-matter counts were acceptable under all storage conditions (except for the 20% mannitol solution, which formed crystals at 5 degrees C and -20 degrees C). An injectable formulation of ofloxacin was stable for at least 3 days at 24 degrees C, 14 days at 5 degrees C, and 26 weeks at -20 degrees C in all tested infusion fluids. Crystals formed in refrigerated or frozen solutions prepared with 20% mannitol injection.     

Stability of cisplatin, iproplatin, carboplatin, and tetraplatin in commonly used intravenous solutions

The stability of cisplatin, iproplatin, carboplatin, and tetraplatin in common intravenous solutions was studied. Admixtures of each drug in each of the following vehicles were prepared in glass containers: 0.9% sodium chloride injection, 5% dextrose injection, 5% dextrose and 0.9% sodium chloride injection, 5% dextrose and 0.45% sodium chloride injection (admixtures were prepared in plastic bags also), and 5% dextrose and 0.225% sodium chloride injection. Drug concentrations were monitored for 24 hours using stability-indicating high-performance liquid chromatographic methods. The stability of cisplatin and tetraplatin was related to the chloride ion content of the infusion fluid; when the infusion fluid contained 0.9% sodium chloride, each of these drugs was present at greater than 90% of the original concentration after six hours. The stability of iproplatin was not related to chloride concentration. A slight increase in the decomposition rate of carboplatin was observed in the presence of chloride ion. Carboplatin and iproplatin are stable for 24 hours in all the infusion fluids studied, but carboplatin should not be diluted with solutions containing chloride ions because of possible conversion to cisplatin. Cisplatin is stable for 24 hours in admixtures containing sodium chloride concentrations of 0.3% or greater. Tetraplatin is stable for six hours in admixtures containing sodium chloride concentrations of at least 0.018%.     

Stability of clindamycin phosphate and ceftizoxime sodium, cefoxitin sodium, cefamandole nafate, or cefazolin sodium in two intravenous solutions

The stability and compatibility of clindamycin phosphate and ceftizoxime sodium, cefoxitin sodium, cefamandole nafate, or cefazolin sodium in two intravenous solutions were studied. Each antibiotic alone as well as each of the four two-drug combinations were examined when mixed in duplicate 100-mL glass bottles of 5% dextrose and 0.9% sodium chloride injections. Antibiotic concentration, pH, and visual appearance were recorded at the time of preparation and at 1, 4, 8, 12, 24, and 48 hours. Antibiotic concentrations were assessed with drug-specific high-performance liquid chromatographic assays. Decreases in concentration of 10% or more from the original concentration were considered to indicate instability. All the single antibiotic solutions were stable for 48 hours. Clindamycin was stable in all combinations except with ceftizoxime in 0.9% sodium chloride injection, which measured 89.3% of its original clindamycin concentration at 48 hours. All the cephalosporins mixed with clindamycin were stable for 48 hours. Clindamycin is stable for at least 48 hours when mixed with cefoxitin sodium, cefamandole nafate, or cefazolin sodium in either 5% dextrose or 0.9% sodium chloride injections and for at least 24 hours when mixed with ceftizoxime sodium in 0.9% sodium chloride injection.     

注射用头孢硫脒与四种常用注射液的配伍稳定性考察

目的 考察注射用头孢硫脒在4种临床常用注射液中的配伍稳定性.方法 根据《中华人民共和国药典》(2010版)规定的注射液pH值的上下限,调节0.9％氯化钠注射液、5％葡萄糖注射液、10％葡萄糖注射液以及5％葡萄糖+0.9％氯化钠注射液的pH值,并按临床常用剂量,配制头孢硫脒与上述注射液及原pH值注射液的配伍溶液,考察上述12种配伍液于0、0.5、1、2、3、4、5、6h的pH值、颜色和澄明度等外观变化,用高效液相色谱法考察在上述时间点下配伍液中头孢硫脒的含量变化.该方法采用BDS-C18(250 mm×4.6 mm,5 μm)色谱柱,磷酸盐缓冲液:乙腈(80∶20)为流动相,检测波长为254 nm,柱温为30℃,进样量1μl.结果 头孢硫脒专属性好,能达到基线分离,线性范围为1～12 mg/ml(R=1.0000),日内精密度相对标准差＜2.0％,12种配伍液在6h内峰面积变化均＜4％.结论 头孢硫脒与不同pH值的0.9％氯化钠注射液、5％葡萄糖注射液、10％葡萄糖注射液以及5％葡萄糖+0.9％氯化钠注射液配伍后稳定,临床上可配伍使用.     

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.     

Temperature of refrigerated i.v. fluids and admixtures during infusion

The effects of infusion rate, drop size, and solution composition on the infusion temperature of i.v. fluids and admixtures that had been stored at refrigerated temperatures were determined. Polyvinyl chloride bags containing 5% dextrose injection, 0.9% sodium chloride injection, cefazolin 20 mg/mL in 5% dextrose injection, or total parenteral nutrient (TPN) solution were removed from the refrigerator after 12 hours and hung from i.v. poles. An administration set was attached to each bag, and the distal end of the administration tubing was placed in a beaker-funnel-flask apparatus that served as a collection vessel for effluent during simulated i.v. infusions. Thermo-couples were inserted into each i.v. bag and positioned under the distal end of each administration set to monitor the temperatures of the solution in the bag and of the effluent. 5% Dextrose injection and 0.9% sodium chloride injection were studied at two flow rates (125 and 60 mL/hr) using two different administration sets (60-drops/mL microdrip set and 15-drops/mL primary set); the cefazolin admixture and the TPN solution were studied at both flow rates using the primary set only. The temperatures at each probe were measured in triplicate at the start of each infusion and at 3, 6, 9, 12, 15, and 25 minutes during the infusion; each infusion was repeated three times. All of the solutions warmed significantly as they passed through the administration sets. Throughout all time intervals, the cefazolin admixtures had the smallest proximal-distal temperature increase, and the TPN solutions had the greatest increase.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Growth of bacteria in intravenous fluids under stimulated actual-use conditions

The growth of microorganisms in nonnutritive intravenous solutions under simulated actual-use conditions was studied. Small quantities of Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae (final concentration 200-400 cells/ml) were injected into 500-ml containers (glass bottles and plastic bags) of 5% dextrose injection, 0.9% sodium chloride injection, and 5% dextrose and 0.9% sodium chloride injection. Additives (ampicillin, vitamin K, lidocaine, and vitamin B complex) were included in some i.v. solutions. Administration sets were attached to the i.v. containers, and the solutions were run into collection bottles; samples were withdrawn at 0, 1, 2, 3, 4, 5, 6, and 8 hours after contamination and plated for viable counts. Staph. aureus and K. pneumoniae remained viable in 5% dextrose injection and in 0.9% sodium chloride injection, but the numbers of these bacteria did not increase. The number of Ps. aeruginosa declined in all three solutions. In 5% dextrose and 0.9% sodium chloride injection, the number of K. pneumoniae declined but Staph. aureus maintained viability. The type of container and the drug additives had no effect on microbial growth, except that ampicillin was bactericidal to Staph. aureus. Low-level contamination of these bacteria in nonnutritive i.v. solutions under actual-use conditions does not result in large numbers of organisms within the time frame in which most solutions are administered.     

The availability of diltiazem: a study on the sorption by intravenous delivery systems and on the stability of the drug

The stability and the sorption by intravenous delivery systems of the calcium antagonist diltiazem dissolved into either 5% dextrose or 0.9% sodium chloride solutions have been investigated, under conditions simulating current clinical practice. Static experiments showed an excellent stability and no sorption after 48 h. Dynamic experiments, at a perfusion rate of 20 mg h-1, showed no sorption of the drug by infusion fluid containers, burettes or administration sets. For end-line filters a temporary decrease of the recovered amount of diltiazem was observed but only with the 0.9% NaCl solution. It is concluded that the stability and the sorption of diltiazem offers no problem with regard to clinical efficacy.