Polyvinyl Chloride Infusion Bags Research Articles

Assessment of Meropenem and Vaborbactam Room Temperature and Refrigerated Stability in Polyvinyl Chloride Bags and Elastomeric Devices

PurposeMeropenem and vaborbactam is an intravenous beta-lactam/beta-lactamase inhibitor combination antibiotic active against multidrug resistant gram-negative bacteria. It may be a suitable treatment for inpatient and outpatient management of infections, and the intravenous admixture stability is therefore important for optimal utilization. The purpose of this study was to determine the stability of meropenem and vaborbactam in polyvinyl chloride (PVC) infusion bags and elastomeric pumps at room and refrigerated temperatures. MethodsMeropenem and vaborbactam vials were reconstituted according to manufacturer instructions and diluted in PVC infusion bags to final concentrations of 4, 8, and 16 mg/mL and in elastomeric pumps to 11.4 mg/mL (n = 5 replicates per concentration and per temperature). PVC bags and elastomeric pumps were stored at room temperature (~24 °C) or in the refrigerator (~4 °C) and sampled over 12 and 144 h, respectively. Stability was defined as the duration that meropenem and vaborbactam concentrations remained ≥90% of the original concentrations. FindingsAll room temperature replicates across the tested concentrations retained meropenem and vaborbactam stability over 12 h and displayed concentration-dependent degradation. Refrigerated studies resulted in meropenem and vaborbactam stability at all tested concentrations up to 120 h. ImplicationsMeropenem and vaborbactam in PVC bags (4, 8, and 16 mg/mL) and elastomeric pumps (11.4 mg/mL) were stable for 12 h at room temperature and 120 h when refrigerated. These stability data allow for enhanced flexibility in the preparation, storage, wastage, and administration of meropenem and vaborbactam in the hospital and outpatient setting.

In-Use Stability of the Rituximab Biosimilar CT-P10 (Truxima®) Following Preparation for Intravenous Infusion and Storage.

CT-P10 is the first biosimilar of the anti-CD20 monoclonal antibody, rituximab. CT-P10 is currently available in over 51 countries worldwide, where it is approved in the same indications as its reference product rituximab. In-use stability studies are conducted for biologics to determine how conditions (e.g., temperature, light, humidity, length of time stored) affect drug quality following dilution and storage in infusion bags. We evaluated the in-use stability of CT-P10 for intravenous infusion stored diluted in infusion bags over longer periods than currently recommended by manufacturer guidelines. CT-P10, within the final month of its 36-month shelf life, was diluted to 1.0 or 4.0mg/mL and stored at 2-8°C in polyethylene or polyvinylchloride infusion bags for 2, 4, and 6 weeks. CT-P10 infusion bags were incubated at room temperature for 24h before analysis. Analyses included detection of sub-visible particles, formation of impurities and determination of charge variants, and heavy- and light-chain content. Cell-based CD20 binding affinity and complement-dependent cytotoxicity were also assessed. Diluted CT-P10 solutions remained clear, colorless, and free of visible particles irrespective of type of infusion bag, target concentration, or timepoint. Protein concentrations, sub-visible particles, pH, osmolality, and molecular weight and charge variants were stable across all timepoints and variables. The binding affinity and potency of CT-P10 remained unchanged, indicating that the efficacy of the antibody was maintained following in-use preparation. We demonstrated that CT-P10 was stable after refrigerated storage for up to 6 weeks followed by incubation at room temperature.

In-Use Physicochemical and Biological Stability of the Trastuzumab Biosimilar CT-P6 Upon Preparation for Intravenous Infusion.

CT-P6 is a biosimilar of trastuzumab, a monoclonal antibody targeting human epidermal growth factor2 (HER2), that is used in the treatment of breast and gastric cancers. The aim of this study was to evaluate the in-use physicochemical and biological stability of CT-P6 following preparation for intravenous (IV) infusion. One batch of CT-P6 within the final month of its 48-month shelf life was used to simulate sub-optimal administration conditions. CT-P6 dilutions of 0.4, 1.0, and 4.0mg/mL, representative of actual use scenarios, were prepared in 0.9% saline solution in either polypropylene (PP) or polyvinylchloride (PVC) infusion bags. Following refrigeration at 2-8°C for 1month, samples were incubated at room temperature for 24h. Physicochemical and biological stability were evaluated according to presence of sub-visible particles, pH, proportion of molecular weight variants, oxidation level of methionine residues 107, 255/256 and 432/433, and binding affinity to the Fc neonatal receptor and HER2. Analyses of CT-P6 preparations at all concentrations tested and in both PP and PVC infusion bags revealed no changes in sub-visible particles, pH, molecular weight variants, oxidation, or potency after 1month at 2-8°C followed by exposure to room temperature for 24h. These analyses demonstrate the extended stability, after refrigerated storage for 1month followed by 24-h exposure to room temperature, of CT-P6 under the dilution conditions required for IV infusion. This stability was sustained for all dilution factors and both infusion bag materials tested.

Visual compatibility of colistin injection with other antibiotics during simulated Y-site administration.

The compatibility of colistin with other antibiotics at concentrations commonly used in intensive care units was studied. A vial of colistin was dissolved in sterile water for injection. The reconstituted solution (colistin base 75 mg/mL) was then diluted in 0.9% sodium chloride injection in polyvinyl chloride (PVC) infusion bag to give a total volume of 100 mL (colistin 1.5 mg/mL). Secondary drugs, including cefoperazone-sulbactam, ceftazidime, ertapenem, fosfomycin, imipenem-cilastatin, linezolid, meropenem, piperacillin-tazobactam, and vancomycin, were reconstituted if necessary and then diluted in 0.9% sodium chloride injection in PVC infusion bags to give final study concentrations of one-hundredth of their initial concentrations. The admixtures were collected in beakers at the end of the i.v. line and stored at 26 °C under constant fluorescent light throughout the study. Compatibility was assessed visually during delivery of each drug pair at time 0 and at 1 hour after starting the infusion. Compatibility was defined as the absence of visually detected particulate formation, haze, precipitation, color change, or gas evolution. Each combination was tested in triplicate. No particulate formation or other evidence of incompatibility was found in any of the studied drug combinations when observed immediately after mixing or at 1 hour. No particulate matter was observed with the unaided eyes, during microscopic evaluation, or against black and white backgrounds. Colistin 1.5 mg/mL was visually compatible with single concentrations of 9 other antimicrobial products during simulated Y-site injection at 26 °C without light protection for at least 1 hour.

Stability of Diluted Iron Polymaltose in PVC Infusion Bags

ABSTRACTBackgroundIn Australia, iron polymaltose (IPM) is the most commonly used parenteral iron therapy for iron deficiency anaemia. Intravenous IPM is prepared by diluting IPM injection with 0.9% sodium chloride. The stability of diluted IPM is not known beyond 24 hours. Therefore, diluted IPM must be prepared on a daily basis, resulting in substantial limitations and problems.AimTo determine the stability of diluted IPM in polyvinyl chloride (PVC) infusion bags at different storage conditions for up to 28 days.MethodIPM 2 mg/mL samples were prepared in 0.9% sodium chloride 500 mL PVC infusion bags. Infusion bags were kept in light protective bags or exposed to artificial light and stored at either 4 °C or 25 °C for up to 28 days. Aliquots were withdrawn immediately after preparation (Day 0) or after Days 1, 2, 3, 6, 7, 14, 21 and 28. Samples were analysed by high‐performance size‐exclusion chromatography to measure the changes in concentration or molecular weight profile of IPM before and after storage. Samples were also investigated for particle size distribution by dynamic light scattering and for the free iron content by ion chromatography.ResultsDiluted IPM remained physicochemically stable (with or without light protection) at room temperature or in the refrigerator for at least 28 days.ConclusionAseptically prepared IPM 2 mg/mL intravenous solution in 0.9% sodium chloride PVC infusion bags was stable for 28 days at room temperature or in a refrigerator.

Stability of levothyroxine injection in glass, polyvinyl chloride, and polyolefin containers

The 24-hour stability of a levothyroxine solution admixed and stored in three common infusion containers and infused through polyvinyl chloride (PVC) tubing was evaluated. Levothyroxine sodium 1-μg/mL injection prepared in glass bottles and PVC and polyolefin bags were assayed using high-performance liquid chromatography at 0, 1, 3, 6, 12, and 24 hours; samples drawn directly from the containers, as well as from the distal end of attached PVC tubing, were assayed. The area under the time-versus-concentration curve (AUC) for predicted and delivered doses was calculated; analysis of variance was used for comparison of the percentages of predicted and actual AUC values. The levothyroxine concentration was stable in glass bottles and polyolefin bags through 24 hours (mean ± S.D. percentage of initial concentration remaining, 103.5% ± 2.5% and 100.0% ± 2.9%, respectively). In the PVC infusion bags, the amount of drug decreased to 90% of the initial concentration within 1 hour and then rose and remained within acceptability limits. The levothyroxine concentration of the samples infused through PVC line from glass and polyolefin containers decreased after 1 hour by about 13%; the loss of the drug from the samples infused from PVC bags was higher (18%), presumably due to additive adsorptive effects. In all samples tested, the drug concentration rebounded and remained above 90% to the end of the study. Levothyroxine sodium 1-μg/mL solution was stable for 24 hours in glass bottles and polyolefin bags but when stored in PVC bags, the concentration decreased by 10% after 1 hour.

Stability of diluted adenosine solutions in polyvinyl chloride infusion bags

The stability of diluted adenosine solutions in polyvinyl chloride infusion bags was studied. Adenosine 50-, 100-, and 220-μg/mL solutions were prepared in 50-mL polyvinyl chloride (PVC) infusion bags containing 0.9% sodium chloride injection or 5% dextrose injection and stored at room temperature (23-25 °C) or under refrigeration (2-8 °C). Each sample of every combination of concentration, diluent, and storage temperature was prepared in triplicate, yielding 36 samples. The samples were assayed using a stability-indicating, reverse-phase high-performance liquid chromatographic method immediately after preparation (time zero) and at 24 hours, 48 hours, 7 days, and 14 days. pH was measured at time zero, 48 hours, 7 days, and 14 days. Time zero concentrations were calculated from the equation produced from a calibration curve of standards ranging from 10 to 500 μg/mL. Samples were also visually inspected against a light background for clarity, color, and the presence of crystalline particulate matter. Stability was defined as retaining at least 90% of the initial adenosine concentration. After 14 days, all samples retained greater than 98% of the initial adenosine concentration, with no evidence of adsorption, visible precipitation, or considerable change in pH, suggesting minimal to no loss of product due to degradation or adsorption. Adenosine 50-, 100-, and 220-μg/mL solutions in 50-mL PVC infusion bags containing 0.9% sodium chloride injection or 5% dextrose injection stored at room temperature and refrigerated conditions were stable for at least 14 days.

Sorption of Drugs by Plastic Infusion Bags

Abstract The sorption of warfarin sodium, various benzodiazepines and a number of other drugs from aqueous solutions by poly vinyl chloride infusion bags was investigated. The sorption kinetics for warfarin and diazepam could be accounted for by a diffusional model in which the loss of drug is determined primarily by the diffusivity of the compound in the plastic matrix. The rate and extent of sorption of warfarin showed a dependence on pH which could be interpreted in terms of ionization of the drug, i.e. only the unionized form was sorbed. A rank order relationship was shown between the initial rate of uptake by the plastic bag and the hexane-water partition coefficients of the compounds. It is suggested that the latter parameter may be useful for the prediction of interactions between a drug substance and polyvinyl chloride infusion bags. Sorption of the compounds by infusion bags made from polypropylene was insignificant except for the highly lipophilic medazepam and accordingly, such bags may be more safe to use than polyvinyl chloride bags in respect to drug sorption.

Physicochemical stability of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride, polyethylene, and polypropylene infusion bags

The physicochemical stability of extemporaneous dilutions of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride (PVC), polypropylene, and polyethylene infusion bags was studied. Oxaliplatin 100 mg/20 mL concentrated solution was diluted in 100 mL of 5% dextrose injection in PVC, polypropylene, and polyethylene infusion bags to produce nominal oxaliplatin concentrations of 0.2 and 1.3 mg/mL. The filled bags were stored for 14 days at 20 degrees C and protected from light, at 20 degrees C under normal fluorescent light, and at 4 degrees C. A 1-mL sample was removed from each bag at time 0 and at 24, 48, 72, 120, 168, and 336 hours. The samples were visually inspected for color and clarity, and the pH values of the solutions were measured. High-performance liquid chromatography was used to assay oxaliplatin concentration. Bacterial contamination was assessed on study day 14 after incubation in trypticase soy solution for three days at 37 degrees C. Solutions of oxaliplatin 0.2 and 1.3 mg/mL in 5% dextrose injection were stable in the three container types for at least 14 days at both 4 degrees C and 20 degrees C without regard to light exposure. No color change was detected during the storage period, and pH values remained stable. No microbial contamination was detected in any samples over the study period. Oxaliplatin solutions diluted in 5% dextrose injection to 0.2 and 1.3 mg/mL were stable in PVC and PVC-free infusion bags for at least 14 days at both 4 degrees C and 20 degrees C without regard to light exposure.

The endocrine disrupting chemical, diethylhexyl phthalate, activates MDR1 gene expression in human colon cancer LS174T cells

Resistance to anticancer drugs is often mediated by the overexpression of P-glycoprotein encoded by the multi-drug resistance (MDR1) gene. The nuclear receptor, steroid and xenobiotic receptor (SXR), is one of the key transcriptional regulators of MDR1 gene expression. A variety of xenobiotics bind to SXR, and stimulate transcription on xenobiotic-response elements (XREs), located in the MDR1 gene promoter. Diethylhexyl phthalate (DEHP) is widely used as a plasticizer for polyvinyl chloride (PVC) medical devices. Previous studies have shown that a significant amount of DEHP leaches from PVC infusion bags and lines during interventions, such as total parenteral nutrition, blood transfusion, and cancer chemotherapy. Thus, the leaching of DEHP during parenteral chemotherapy for cancer patients may facilitate MDR1 expression in various tissues, including cancer cells, which may promote drug resistance. To examine such a hypothesis, the effect of DEHP on SXR-mediated transcription of the MDR1 gene was studied in the human colon adenocarcinoma-derived cell line, LS174T cells, which endogenously express SXR. DEHP increased the SXR-mediated transcription of the MDR1 gene in luciferase-reporter assays. The induction by DEHP was abrogated when a reporter plasmid containing mutated DR+4 motif in the XRE was used. In a mammalian two-hybrid assay, DEHP recruited steroid receptor co-activator-1 to the ligand-binding domain of SXR. Finally, using real-time reverse transcriptase-PCR, we showed that DEHP increased MDR1 gene expression in a dose-dependent manner. We conclude that DEHP is an inducer of the MDR1 gene in this cell line. As such, the leaching of DEHP from the PVC medical devices may influence the MDR1 expression, which may induce resistance to drugs in certain populations of cancer cells.

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.

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.

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 bryostatin 1 in infusion devices.

Bryostatin 1 is currently in phase II clinical trial sponsored by the National Cancer Institute as an anticancer chemotherapeutic agent. Bryostatin 1 for injection was supplied in a dual pack containing a drug vial and a diluent vial and was manufactured by Ben Venue Laboratories, Inc (Bedford, OH). The stability and compatibility of the bryostatin 1-PET formulation, diluted to 1 and 10 ug/mL in saline and benzyl alcohol preserved saline, with polypropylene (PP) and polyvinyl chloride (PVC) bags at room temperature (27 degrees C) were studied. All experiments were conducted in triplicate and analyses were performed using a validated, stability-indicating, high performance liquid chromatography (HPLC) assay. Bryostatin 1 solutions were compatible with PP bags. At both concentrations and with both salines, the bryostatin content remained unchanged during the 28-day storage period, benzyl alcohol concentration in the preserved saline solutions also remained relatively constant. In PVC bags, however, a decrease in bryostatin 1 concentrations without generation of decomposition products was observed at both dilutions and with both salines during the 28-day storage. A decrease in benzyl alcohol concentration in the preserved saline was also observed. While no diethylhexylphthalate (DEHP) leakage into the solution was observed in PP bags, DEHP leakage in PVC infusion bags was observed on day 2 of storage which increased with storage time and leveled off on day 6. The amount of DEHP leached into drug solution is dependent on the drug concentration. This study suggests bryostatin-PET formulation diluted with preserved saline can be used for long-term (4 week) intravenous administration using PP infusion bags, but not with PVC bags.

Stability of thiotepa (lyophilized) in 0.9% sodium chloride injection.

The stability of thiotepa in a new formulation of the drug was studied. Vials of Thioplex (Immunex), a relatively new lyophilized formulation of thiotepa, were reconstituted with sterile water and diluted with 0.9% sodium chloride injection in polyvinyl chloride infusion bags to thiotepa concentrations of 0.5, 1, and 3 mg/mL. The solutions were stored at 8 and 25 degrees C in ambient light and analyzed at 0, 8, 24, and in most cases 48 hours for thiotepa concentration and chloro-adduct formation by stability-indicating high-performance liquid chromatography. Thiotepa 1 and 3 mg/mL was stable for 48 hours at 8 degrees C and for 24 hours at 25 degrees C. Thiotepa 0.5 mg/mL was not stable at either temperature. Storage at 8 degrees C slowed but did not prevent chloro-adduct formation and loss of potency. The pH tended to increase with time; turbidity remained low. Thiotepa (lyophilized) 1 and 3 mg/mL in 0.9% sodium chloride injection was stable for 48 hours at 8 degrees C and for 24 hours at 25 degrees C; the drug was unstable when diluted to 0.5 mg/mL and stored under the same conditions.

Stability and compatibility of topotecan hydrochloride for injection with common infusion solutions and containers

The stability and compatibility of topotecan hydrochloride with common infusion solutions and containers were studied. During this study, the leaching of diethylhexyl phthalate (DEHP), a major plasticizer of some polyvinyl chloride (PVC) materials was also investigated. A formulation of topotecan hydrochloride was added to 50 ml PVC infusion bags, polyolefin infusion bags and 150 ml glass bottles containing either 5% dextrose injection or 0.9% sodium chloride injection at an initial nominal topotecan concentration of 0.05 mg ml −1. Additionally, the topotecan hydrochloride formulation was added to 50 ml PVC infusion bags containing either 5% dextrose injection or 0.9% sodium chloride injection at an initial nominal topotecan concentration of 0.025 mg ml −1. Containers were maintained at 5°C for 7 days or 23–24°C for 24 h. Samples were analyzed using a stability-indicating HPLC method to determine the concentration of topotecan and the presence of any degradates. The samples were also analyzed by separate HPLC methods to detect the presence of DEHP and the hydrolyzed lactone ring form (SKF 105992) of topotecan hydrochloride. In addition, the pH of each sample was measured initially and at the end of the storage time. There was no significant loss of topotecan observed for any of the conditions studied and no significant increase in degradates was observed. The pH remained unchanged for all samples between the start and end of the study. At the concentrations studied, topotecan hydrochloride was stable for up to 24 h at room temperature and for up to 7 days at 5°C, in PVC and polyolefin infusion bags and glass bottles containing either 5% dextrose injection or 0.9% sodium chloride injection. The presence of topotecan hydrochloride did not contribute to leaching of DEHP in the PVC infusion bags.

The extraction of diethylhexylphthalate (DEHP) from polyvinyl chloride components of intravenous infusion containers and administration sets by paclitaxel injection

Paclitaxel injection (Taxol TM) contains cremophor and ethanol in equal proportions, two agents known to leach diethylhexylphthalate (DEHP) from polyvinyl chloride (PVC) infusion bags and administration sets. The manufacturers of paclitaxel therefore recommend the use of glass, polypropylene or polyolefin containers for storage. This recommendation poses a number of practical problems since the availability of these other types of containers is severely limited and as such staff may be unfamiliar in their handling. The aim of this study was to investigate the extent of DEHP extraction by paclitaxel injection contained in PVC infusion bags and administered by either PVC or non-PVC sets in a bid to verify the manufacturers' recommendations to avoid using PVC containers. The results indicated that during a 3 h infusion period, increasing amounts of DEHP were leached into the paclitaxel vehicle from both the PVC infusion bags and the standard PVC sets. The amounts of DEHP extracted depended on the concentration of the paclitaxel vehicle, the length of contact between the injection vehicle and the container and the type of administration set used. DEHP concentration was at its lowest when a non-PVC set was used to administer the infusate. The addition of 300 and 600 mg paclitaxel to the infusate, administered by non-PVC sets, led to no significant increase in DEHP extraction. Comparative total amounts of DEHP extracted for each dose were 10.0 and 30.3 mg for the paclitaxel vehicle infusion through non-PVC sets and 13 and 30.5 mg respectively for the formulated drug plus vehicle. These amounts of DEHP are substantially less than those delivered during a blood transfusion. Furthermore, the possibility of chronic exposure to DEHP from paclitaxel administered under these conditions is negligible in patients receiving the drug on four to six occasions. The study concludes that there is only minimal risk of DEHP exposure from paclitaxel infusion contained in PVC bags and administered through non-PVC administration sets.

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.

The effect of each of three physicochemical variables on solute uptake by polyvinylchloride infusion bags

The effect of each of three physicochemical variables, solute concentration, electrolyte concentration and temperature on the uptake of six model solutes by Polyvinylchloride (PVC) infusion containers has been investigated. It has been shown that the solute uptake is independent of the initial concentration of the solute and that both temperature and electrolyte concentration have significant effects on the extent of solute loss. The Arrhenius equation has been used to described the temperature effect on solute uptake into PVC bags. The extent of solute uptake from solution in the presence of electrolytes without large ions is a function of increasing ionic strength. It is suggested that the sorption number which can be used to predict solute uptake needs to be adjusted by the use of correction factors for temperature and for vehicle ionic strength, as appropriate.

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)