Polyvinyl Chloride Administration Sets Research Articles

可塑剤ＤＥＨＰを溶出する恐れのある注射薬における輸液セットの対策についての一考察―医療施設の現状調査および看護師の意識調査―

It is widely known that lipid-soluble injections (e.g. Paclitaxel) elute di (2-ethylhexyl) phthalate (DEHP), a plasticizer used in polyvinyl chloride (PVC) administration sets. A survey of the current situation in medical facilities revealed that 50% did not take adequate measures against this and in most of them, pharmacists were not involved in selecting administration sets. In the case of Kobe Teishin Hospital, the Medical Treatment Safety Management Committee decided to provide Paclitaxel and other injections together with PVC administration sets containing tris (2-ethylhexyl) trimellitate (TOTM), a plasticizer, which is less easily eluted than DEHP, in accordance with doctors' instructions. A questionnaire survey of hospital nurses conducted to compare the situation between before and after providing the TOTM sets revealed that their provision had eliminated the confusion nurses felt when administering injections and reduced the stock of administration sets. In conclusion, our findings show that it is necessary for pharmacists be involved in the selection of medical equipment for administering drugs to help ensure safety, that drugs are used properly, and economic use of resources.

Investigation of the release behavior of DEHP from infusion sets by paclitaxel-loaded polymeric micelles

The current clinical formulation of paclitaxel (Taxol ®) contains 1:1 blend of Cremophor ® EL (polyethoxylated castor oil) and dehydrated ethanol. Cremophor ® EL and dehydrated ethanol are well known to leach di-(2-ethylhexyl) phthalate (DEHP) from polyvinyl chloride (PVC) infusion bags and PVC administration sets. DEHP is a possible hepatotoxin, carcinogen, teratogen and mutagen. Long-term exposure to DEHP may cause health risks. As an alternative formulation for paclitaxel, paclitaxel-loaded polymeric micelles (PLPM), made of monomethoxy poly(ethylene glycol)-block-poly( d, l-lactide) (mPEG-PDLLA) diblock copolymer, has demonstrated clear advantages over Taxol ® in pharmacokinetics and therapeutic index. Paclitaxel in either PLPM or Taxol ® formulations, diluted in 0.9% sodium chloride injection, was stable in the PVC infusion bags. The PLPM formulation significantly reduced the amount of DEHP extracted from PVC infusion bags and PVC administration sets. For PLPM diluted in 0.9% sodium chloride injection, the total amount of DEHP delivered over the simulated infusion period was 0.7 mg for 3 h and 2.0 mg for 24 h, which was less than 2.9% of the DEHP extracted by Taxol ®. These results confirmed that there is negligible risk of DEHP exposure from diluted PLPM i.v. infusion using PVC infusion bags and PVC administration sets.

界面活性剤による輸液セットからのジエチルヘキシルフタレートの溶出の検討

Diethylhexyl phthalate (DEHP) is used in administration sets made of polyvinylchloride (PVC) as a plasticizer and such PVC administration sets are used frequently for intravenous drip infusions. However, it has been reported that the DEHP in administration tubes is dissolved by intravenous solutions containing solubilizing agents to aid continuous intravenous infusion. Since DEHP is suspected of being an endocrine disruptor, it should be prevented from entering the human body. With this in mind, we examined the DEHP leaching characteristics of a model solution containing the surfactant polyoxyethylated castor oil as the solubilizing agent. DEHP began to be leached from the administration set when the continuous infusion was started and the amount of DEHP leaching was found to increase in proportion to the concentration of the solubilizing agent, but decrease when the rate of flow was increased. The DEHP leaching pattern was similar when the model solution contained drugs. From these findings, we inferred that DEHP leaching is greatly influenced by the solubilizing agent. Though there have been no reports of DEHP having adverse effects, it should be prevented from entering the human body through the use of administration sets that do not contain it or changing the administration procedure.

経腸経管栄養療法時におけるポリ塩化ビニル製チューブからのフタル酸ジ‐２‐エチルヘキシルの溶出

Di-2-ethylhexyl Phthalate (DEHP) was reported to dissolve from a polyvinyl chloride (PVC) administration tube during the infusion of an injection fluid containing a solvilizing agent, soybean oil or lecithin, etc. This paper describes the behavior of DEHP dissolution from PVC tubes during enteral tube feeding. The DEHP concentration was determined using HPLC. After the passage the ENSURE LIQUID® (EL) solution through the PVC tube, DEHP was dissolved in the EL solution. The EL solution is one type of enteral nutrition. This dissolution pattern was similar to that of injection fluid containing a solvilizing agent, in which the DEHP concentration in the EL solution increased linearly over time at first and thereafter reached a plateau. 170 μg of the DEHP was dissolved after 200mL of the EL solution had passed through the PVC administration set (the drip conditions were 25°C, 100mL/hr, tube length 115cm and inner diameter 0.3cm). The amount of DEHP which dissolved into the solution depended on the temperature (25-40°C), and no clear difference was observed between the PVC tubes (administration tube, feeding tube). In addition, the amount of DEHP that dissolved into the solution varied depending on the type of enteral nutrition.

Stability, compatibility and plasticizer extraction of quinine injection added to infusion solutions and stored in polyvinyl chloride (PVC) containers

The stability of quinine was determined in various diluents and in polyvinyl chloride (PVC) containers. The release of diethyhexyl phthalate (DEHP) from PVC bags into intravenous infusions of quinine was also measured. We used an injection of two doses of quinine; quiniforme at 500 mg and quinimax at 400 mg in either 250- or 500-ml PVC infusion bags containing 5% dextrose, to give initial nominal concentrations of 2 or 1 mg ml −1 quiniforme and 1.6 or 0.8 mg ml −1 quinimax, the mean concentrations commonly used in clinical practice. Samples were assayed by stability-indicating high-performance liquid chromatography (HPLC) and the clarity was determined visually. Experiments were conducted to determine whether the stability and compatibility of quinine would be compromised, and whether DEHP would be leached from PVC bags and PVC administration sets during storage and simulated infusion. There was no substantial loss of quiniforme and quinimax over 1- or 2-h simulated infusion irrespective of the diluent, and storage during 8 h at 22°C, 48 or 72 h at 4°C and 96 h at 45°C. Leaching of DEHP was also detected during simulated infusion delivery using PVC bags and PVC administration sets. The quantity was less than 2 μg ml −1. During storage at 4°C and room temperature the leaching of DEHP was low, but when the temperature was 45°C the quantity was high, 21 μg ml −1. To minimise patient exposure to DEHP, quinine solutions with all drugs should be infused immediately or stored for a maximum of 48 h at 4°C.

Compatibility and stability of aplidine, a novel marine-derived depsipeptide antitumor agent, in infusion devices, and its hemolytic and precipitation potential upon i.v. administration.

Aplidine is a novel marine-derived antitumor agent isolated from the Mediterranean tunicate Aplidium albicans. The compound is pharmaceutically formulated as a lyophilized product containing 500 microg active substance per dosage unit. Prior to i.v. administration it is reconstituted with a solution composed of Cremophor EL, ethanol absolute and Water for Injection (15/15/70% v/v/v) with further dilution in 0.9% w/v sodium chloride for infusion (normal saline). The aim of this study was to investigate the compatibility of aplidine infusion solutions with polyvinyl chloride (PVC)-containing and PVC-free administration sets, and to determine the stability of aplidine after reconstitution and further dilution in infusion solutions. Furthermore, in vitro biocompatibility studies to estimate the hemolytic and precipitation potential of aplidine infusion solutions upon i.v. administration were conducted. In this study we show that sorption of aplidine to PVC and to a lesser extent to PVC-free administration set materials occurs. Also, most probably due to the presence of Cremophor EL in the infusion solution, significant leaching of diethylhexyl phtalate (DEHP) from the PVC administration set occurs. After reconstitution and dilution the drug is stable for at least 24 and 48 h, respectively, in glass containers when stored at room temperature (20-25 degrees C) and ambient light conditions. We found that aplidine should be administered in infusion concentrations equal or above 28.8 microg/ml using a PVC-free administration set consisting of a glass container and PVC-free infusion tubing. After reconstitution it must be diluted further with normal saline within 24 h after preparation and subsequently administered to the patient within 48 h. Additionally, results from the biocompatibility studies show that neither hemolysis nor precipitation of aplidine is expected upon i.v. administration.

Stability study of fotemustine in PVC infusion bags and sets under various conditions using a stability-indicating high-performance liquid chromatographic assay

The stability and compatibility of fotemustine, a nitrosourea anticancer agent, in 5% dextrose solution with polyvinyl chloride (PVC) containers and administration sets were studied under different conditions of temperature and light. The drug was diluted to 0.8 and 2 mg ml −1 in 100 or 250 ml 5% dextrose injection solutions for 1-h simulated infusions using PVC bags and administration sets with protection from light. After preparation in the PVC bags containing 5% dextrose, fotemustine was also prepared at the same concentrations and stored at 4°C for 48 h and at room temperature (22°C) or at sunray exposure (>30°C) over 8 h with or without protection from light. The solution samples were removed immediately at various time points of simulated infusions and storage, and stored at −20°C until analysis. The physical compatibility with PVC and chemical stability in solution of fotemustine were assessed by visual examination and by measuring the concentration of the drug in duplicate using a stability-indicating high-performance chromatographic assay. When admixed with a 5% dextrose solution, fotemustine 2 and 0.8 mg ml −1 was compatible and stable over 1-h of simulated infusion using PVC bags through PVC administration sets with protection from light. On the other hand, in the same diluent, fotemustine was compatible and stable with PVC bags for at least 8 h at 22°C with protection from light and for at least 48 h at 4°C with protection from light. There were no pH variation, no visual change, no color change, no visible precipitation and no loss of the drug. Conversely, when the solutions were exposed to light (ambient or solar), the drug concentration decreased rapidly, leading to the production of a degradation product as shown by mass spectral analysis and a discoloration of the solutions. Finally, in all cases, no DEHP (di-2-ethylhexyl phthalate) was detected in the injection solution.

Compatibility and stability of vancomycin hydrochloride with PVC infusion material in various conditions using stability-indicating high-performance liquid chromatographic assay

The stability and compatibility of vancomycin hydrochloride injection in various diluents with polyvinyl chloride (PVC) containers were studied under different conditions of temperature and light. Drug was diluted to 5 mg/ml and 8 mg/ml in injection solutions for 1 and 24 h-simulated infusions. Vancomycin hydrochloride injection was also prepared to 5 mg/ml in PVC bags and stored at 4°C over 7 days with protection from light and at 22°C over 48 h without protection from light. Physical compatibility with PVC and chemical stability in solution of vancomycin were assessed by visual examination and by measuring the concentration of drug in duplicate with stability-indicating high-performance chromatographic assay. There were no visual change, no color change, no visible precipitation and no loss of the drug. When admixed in 0.9% sodium chloride injection or 5% dextrose injection, vancomycin hydrochloride 5 and 8 mg/ml was compatible and stable for 1 and 24 h, respectively, of simulated infusion using PVC bags through PVC administration sets without protection from light. On the other hand, in the same diluents, vancomycin hydrochloride 5 mg/ml was compatible and stable with PVC bags for at least 48 h at 22°C without protection from light and for at least 7 days at 4°C with protection from light.

Stability, compatibility and plasticizer extraction of miconazole injection added to infusion solutions and stored in PVC containers

The stability of miconazole in various diluents and polyvinyl chloride (PVC) containers was determined and the release of diethylhexyl phthalate (DEHP) from PVC bags into intravenous infusions of miconazole was measured. An injection formulation (80 ml) containing a 1% solution of miconazole with 11.5% of Cremophor EL was added to 250-ml PVC infusion bags containing 5% glucose injection or 0.9% sodium chloride injection, to give an initial nominal miconazole concentration of 2.42 mg ml −1, the mean concentration commonly used in clinical practice. Samples were assayed by stability-indicating high-performance liquid chromatography (HPLC) and the clarity was determined visually. Experiments were conducted to determine whether the stability and compatibility of miconazole would be compromised, and whether DEHP would be leached from PVC bags and PVC administration sets during storage and simulated infusion. There was no substantial loss of miconazole over 2 h simulated infusion irrespective of the diluent, and over 24 h storage irrespective of temperature (2–6°C and 22–26°C). All the solutions initially appeared slightly hazy. Leaching of DEHP was also detected during simulated delivery using PVC bags and PVC administration sets. There was a substantial difference between the amounts of DEHP released from PVC bags and from administration sets, and also between the amounts released in solutions stored in PVC bags at 2 6°C and 22–26°C over 24 h. At the dilution studied, miconazole was visually and chemically stable for up to 24 h. The storage of miconazole solutions in PVC bags seems to be limited by the leaching of DEHP rather than by degradation. To minimize patient exposure to DEHP, miconazole solutions should be infused immediately after their preparation in PVC bags.

Clinical response to intravenous nitroglycerin infused through polyethylene or polyvinyl chloride tubing

The effects of polyethylene and polyvinyl chloride (PVC) administration sets on the clinical response to i.v. nitroglycerin were studied. Patients with ischemic heart disease were randomly assigned to receive nitroglycerin solution through either a polyethylene administration set or a PVC set. The rate of the infusion was 5-10 micrograms/min initially and was adjusted upward by 5-10 micrograms/min every 5-10 minutes until anginal symptoms were relieved or an adverse effect limited further increases. The data collected included patient demographics, the indication for nitroglycerin, nitroglycerin dosages, the initial dosage-adjustment time (the time necessary to reach the initial effective dosage), the number of dosage adjustments and the indications for them, the duration of the infusion, the time of tubing changes, the total dose of nitroglycerin, the amounts of sublingual nitroglycerin and i.v. morphine used, and the occurrence of various clinical events. There were 78 courses of therapy in the PVC group and 62 in the polyethylene group. The two groups were comparable in all respects except gender. There were no significant differences between the two groups in any of the primary study variables. Patients who received i.v. nitroglycerin through a PVC administration set had the same clinical response as patients given the drug through a polyethylene set.

Stability, compatibility, and plasticizer extraction of taxol (NSC-125973) injection diluted in infusion solutions and stored in various containers

The stability of taxol (NSC-125973) in various diluents and containers was determined, and the extent of leaching of di(2-ethylhexyl) phthalate (DEHP) from polyvinyl chloride (PVC) bags caused by the taxol formulation was measured. A taxol formulation consisting of a 6-mg/mL solution of taxol in 50% polyoxyethylated castor oil and 50% dehydrated ethanol was added to 50- and 100-mL glass bottles, PVC infusion bags, and polyolefin containers containing 5% dextrose injection or 0.9% sodium chloride injection to give initial nominal taxol concentrations of 0.3, 0.6, 0.9, and 1.2 mg/mL. The containers were maintained at 20-23 degrees C for 12-24 hours. Samples were assayed by stability-indicating high-performance liquid chromatography, and clarity was determined visually. An experiment was run to ascertain whether DEHP would leach from a PVC administration set during a simulated infusion. There was no substantial loss of taxol over 24 hours. Filtration through a membrane resulted in no loss of taxol. All the solutions initially appeared hazy. Solutions stored in PVC bags became more hazy with time than solutions stored in glass or polyolefin containers. The haze seen in PVC bags was traced to leaching of DEHP. Agitation had no effect on the extent of leaching. Leaching was also seen during simulated delivery through PVC administration sets. No DEHP was detected when solutions were stored in glass or polyolefin containers and infused through polyethylene-lined sets. At the dilutions studied, taxol was visually and chemically stable for up to 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

A Comparative Analysis of the Loss of Amiodarone from Small and Large Volume PVC and Non-PVC Infusion Systems

The time-course of the adsorption of amiodarone hydrochloride onto flexible polyvinyl chloride (PVC) infusion bags and administration sets has been studied under ambient conditions similar to the intensive and coronary care units at the Repatriation General Hospital--Daw Park. When admixtures containing 900-1000 mg amiodarone hydrochloride in 500 ml PVC infusion bags containing glucose 5% were assayed, a minimal (2.7%) loss of amiodarone was detected at 24 hours compared with glass infusion bottles. There was no loss apparent when 100 ml PVC infusion bags were used compared with 100 ml glass bottles. When PVC administration sets were attached to 500 ml glass infusion bottles, maximal adsorption losses of up to 4.9% were observed in the effluent within one hour of the commencement of the simulated infusion. In Australia, the current recommendations by the distributor of amiodarone, Reckitt & Colman Pharmaceuticals, advise that the administration of amiodarone should be via glass infusion bottles or rigid PVC plastic containers without plasticisers together with non-PVC administration lines. These results do not support this recommendation.

Factors affecting diazepam availability from intravenous admixture solutions.

The authors studied the availability of parenteral solutions of diazepam in glass bottles or polyethylene (PE) containers during infusion through polyvinyl chloride (PVC) administration sets. Diazepam solutions in concentration of 1000 mg/500 ml in 0.9% sodium chloride (NS) and 5% glucose (G5W) injection were infused at a flow rate of 30 ml/h, and samples were taken from the bottle and at the end of the administration set, till 12 hours of infusion. The samples were tested in triplicate using ultraviolet spectrophotometry. The greatest loss of diazepam was observed in all solutions at 30 minutes of infusion (63.5% G5W glass, 60.5% NS glass, 55% G5W PE and 58% NS PE from the original concentration of 200 micrograms/ml). The diazepam concentrations in the containers did not significantly changed. The loss of diazepam from solutions infused through PVC administration sets should be kept in mind in severe clinical situations as status epilepticus, tetanus and eclampsia.

Effect of flow rate and type of i.v. container on adsorption of diazepam to i.v. administration systems

The effect of flow rate and type of i.v. solution container on adsorption of diazepam to i.v. administration systems was studied. Diazepam solutions were prepared in 500 mL of 0.9% sodium chloride injection in glass, polyethylene, and polyvinyl chloride (PVC) containers to a final theoretical concentration of 50 micrograms/mL. PVC administration sets were attached to the containers, and diazepam solution was infused at flow rates of 30, 45, 60, 90, and 120 mL/hr. Solution samples were taken initially and at 0.25, 0.5, 0.75, 1.00, 1.50, 2.00, 3.00, and 4.00 hours after infusion of the first 5 mL of solution through the system. Three infusion trials were performed using each type of container. Adsorption of diazepam to each type of container was evaluated by serial measurements of diazepam concentration over a 168-hour period using five containers of each type. The effect of shaking the container on diazepam adsorption to PVC containers was tested by comparing concentrations in five containers that were shaken during a two-hour period with concentrations in five unshaken containers. Diazepam concentrations were measured spectrophotometrically in duplicate. Diazepam concentrations in glass containers remained unchanged throughout the 168-hour study period; concentrations decreased by about 5% in polyethylene containers and as much as 75% in PVC bags. Shaking increased diazepam adsorption to the PVC container. In the infusion trials, the percentage of diazepam adsorbed increased as flow rate decreased. The amount of diazepam adsorbed to the i.v. administration system was ore dependent on flow rate and infusion time than on the type of container used.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of tubing length on adsorption of diazepam to polyvinyl chloride administration sets

The effect of administration-set tubing length on adsorption of diazepam to polyvinyl chloride (PVC) tubing was studied, and a simple equation for calculating the dose of diazepam delivered to the patient during an i.v. infusion of diazepam was derived. Diazepam solutions were prepared in 500 mL of 0.9% sodium chloride injection in glass bottles to a final theoretical concentration of 50 micrograms/mL. PVC administration sets were attached to the bottles, and the tubing was then cut to various lengths or the entire length was used for infusion of diazepam solution at a constant rate of 60 mL/hr. Samples of the diazepam solution were collected in glass test tubes initially and after infusion periods of 0.25, 0.5, 0.75, 1.00, 1.50, 2.00, 3.00, and 4.00 hours. Diazepam concentrations were assayed spectrophotometrically in duplicate, and each infusion trial was performed three times. The mean diazepam concentrations in the bottles remained within 100 +/- 1% of initial concentration throughout the study. However, solution samples collected after the four-hour infusion period varied in concentration from 45.5 micrograms/mL using the 23-cm length of tubing to 28.8 micrograms/mL using the entire (185-cm) tubing. Also, the percentage of diazepam adsorbed to the tubing increased as the infusion time decreased. A biexponential equation based on the adsorption data obtained for various tubing lengths was successfully used to calculate the percentage of the theoretical diazepam dose delivered through the tubing during different infusion times. To minimize the adsorption of diazepam to PVC administration sets, the shortest possible length of administration-set tubing should be used.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of pretreatment with 0.9% sodium chloride or insulin solutions on the delivery of insulin from an infusion system

The effect of pretreating a polyvinyl chloride i.v. administration system with sodium chloride or insulin solution on the delivery of insulin was studied. Insulin labeled with iodine 125 was added to human insulin, which was added to 0.9% sodium chloride injection packaged in flexible polyvinyl chloride containers and to 0.9% sodium chloride injection placed in empty ethylene vinyl acetate containers. Samples were tested for insulin content by gamma spectrometry after storage in the bags and after infusion through four different polyvinyl chloride administration sets at different flow rates. Effluent samples were collected at 10 times (6-50 minutes) after the start of the infusion. The 0.9% sodium chloride injection had a conditioning effect on the polyvinyl chloride administration sets, indicating an electrostatic sorption mechanism for insulin. Sorption to the untreated polyvinyl chloride sets and the ethylene vinyl acetate bags was substantial and followed a Langmuir adsorption isotherm. Insulin sorption to the untreated administration sets was greatest from the first 100 mL of effluent and did not differ by flow rate or type of set investigated. Storing the sodium chloride injection in the tubing for one hour or flushing the tubing with 100 mL of sodium chloride injection or 100 mL of the insulin admixture decreased sorption by half. Storing the insulin admixture in the tubing for 30 minutes caused sorption to be reduced by a factor of three. When either of the solutions was stored in the set and then the set was flushed with the solution, sorption was even further suppressed.(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 and availability of cyclosporine in 5% dextrose injection or 0.9% sodium chloride injection

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

Sorption of amiodarone to polyvinyl chloride infusion bags and administration sets

The loss of amiodarone from i.v. admixtures to flexible polyvinyl chloride (PVC) infusion bags and i.v. administration sets was studied. Admixtures containing amiodarone hydrochloride 600 micrograms/mL and either 5% dextrose injection or 0.9% sodium chloride injection were stored at room temperature in glass bottles (both with and without contact of the drug solution with the rubber bottle closure), in flexible PVC bags, or in rigid PVC bottles. After 120 hours, the contents of each flexible PVC bag were emptied and replaced by methanol, which was allowed to remain in the bag for an additional 120 hours and was then analyzed for amiodarone content. To determine availability of amiodarone after infusion through a 1.8-m PVC i.v. administration set, solutions stored in glass containers were run through the set at 0.5 mL/min for 90 minutes. Samples of drug solutions were collected at appropriate intervals and analyzed by a stability-indicating high-performance liquid chromatography (HPLC) assay. Admixtures containing 0.9% sodium chloride injection were not stable; visual incompatibility was evident after 24 hours of storage in glass bottles, and no further testing was performed. In admixtures containing 5% dextrose injection that were stored in 50-mL flexible PVC bags, 60% of the initial amiodarone concentration remained after 120 hours; approximately half of the lost drug was recovered with the methanol. In effluent collected from the PVC administration set, 82% of the initial amiodarone concentration remained. Amiodarone concentrations did not decrease appreciably, after storage in glass or rigid PVC bottles, indicating that drug loss was probably affected by the plasticizer, di-2-ethylhexyl phthalate.(ABSTRACT TRUNCATED AT 250 WORDS)