Long-term physicochemical stability of 5-fluorouracil at selected standardised rounded doses in polyolefin bags.

BACKGROUND: Chemotherapy doses are usually prescribed on the basis of body surface area but dose banding is emerging as an efficient alternative. Dose banding presents the possibility of in-advance preparation in a Centralized Intravenous Admixture Service. AIM OF THE STUDY: To evaluate the long-term stability of 5-fluorouracil at banded doses (700 mg and 800 mg) in polyolefin bags. MATERIALS AND METHODS: Ten polyolefin bags were prepared under aseptic conditions and stored at 23 ± 2°C for 24 days. Five of them were composed of 14 mL 5-fluorocuracil (700 g) in 100 mL 0.9% sodium chloride solution and the five other of 16 mL 5-fluorouracil (800 mg) in 100 mL 0.9% sodium chloride solution. At defined times, physical stability parameters were assessed: optical densities, pH measurements, visual and microscopical inspections. Solutions concentrations were measured using high-performance liquid chromatography coupled with a photodiode array detector. RESULTS: No change was observed on pH and optical density measurements during the study period. Visual and microscopical inspections remained free of colour change, precipitate, microagregate or crystal. The concentrations of 5-Fluorouracil in 800 mg bags remained stable for 24 days while the concentration in 700 mg bags showed a stability of at least 17 days. CONCLUSION: Five-fluorouracil at banded doses of 700 and 800 mg in polyolefin bags is physicochemically stable for at least 17 days at 23 ± 2°C. These results support the possibility of in advance centralised preparation.

Long term stability of an admixture of alizapride and ondansetron in 0.9% sodium chloride solution polyolefin bags stored at 5±3°C.

BACKGROUND: Patients undergoing chemotherapeutic treatment are currently treated by a concomittent infusion of alizapride and ondansetron. To optimise the procedure and to ensure patients' safety, the admixture could be prepared in advance by the Centralized Intravenous Additive Service (CIVAS) provided that the stability of the mixture has been proven beforhand to reduce nausea and vomiting.Aim of the study: to evaluate the long-term stability of an admixture of alizapride 0.926 mg/l and ondansetron 0.074 mg/ml in 0.9% sodium chloride polyolefin bags stored at 5 ± 3°C. MATERIAL AND METHODS: Five polyolefin bags containing 100 ml sodium chloride 0.9% added with 4 ml alizapride (100 mg) and 4 ml ondansetron (8 mg) were prepared in aseptic conditions and stored at 5 ± 3°C for 56 days. Periodically, physical stability tests were performed including: pH measurements, optical density measurements at 350, 410 and 550 nm to track turbidity appearance, visual and microscopical inspections to detect colour changes, precipitation, microaggregates or crystals. The concentrations of the solutions were measured by High Performance Liquid Chromatography coupled with an UV detector. RESULTS: There was no change in pH and optical densities during the study period. Visual and microscopical inspections didn't show any change of colour neither precipitation, microaggregate or crystal. The alizapride and ondansetron concentrations remained stable over the study. CONCLUSION: The admixture of alizapride and ondansetron in 0.9% sodium chloride solution polyolefin bags is physicochemically stable up to 56 days at 5 ± 3°C. These results support the possibility of preparing the solutions in advance by a CIVAS.

Stability and compatibility of vancomycin for administration by continuous infusion.

BACKGROUND: Vancomycin is increasingly used by continuous infusion, but few specific data are available about stability under practical conditions of preparation and use, and compatibility with other intravenous drugs commonly used in the routine hospital setting. METHODS: Vancomycin stability [defined as recovery ≥ 93% of the original content (validated HPLC assay)] was examined throughout the whole process of centralized preparation, storage and use in the ward by infusion for up to 48 h, with allowances for deviations from recommended practice [exposure to high temperature; use of concentrated solutions (up to 83 g/L)]. Compatibility was assessed by mimicking co-administration in a single line via Y-shaped connectors with contact of 1 h at 25°C, followed by visual inspection (professional viewer), detection of particulate matter (particle analyser) and HPLC assay of vancomycin. RESULTS: Vancomycin was stable during the whole process and also during 72 h exposure of concentrated solutions at temperatures up to 37°C. Major incompatibilities were seen with ß-lactams (temocillin, piperacillin/tazobactam, ceftazidime, imipenem, cefepime and flucloxacillin) and moxifloxacin, but not with ciprofloxacin, aminoglycosides and macrolides. Propofol, valproic acid, phenytoin, theophylline, methylprednisolone and furosemide were also incompatible, whereas ketamine, sufentanil, midazolam, morphine, piritramide, nicardipine, urapidil, dopamine, dobutamine and adrenaline were compatible. No effect or incompatibility with N-acetyl-cysteine or amino acid solutions was detected. CONCLUSIONS: Centralized preparation of vancomycin and its use by continuous infusion in wards is safe concerning stability, but careful attention must be paid to incompatibilities. Several drugs (including all ß-lactams) require distinct intravenous lines or appropriate procedures to avoid undue contact.

Doxorubicin-loaded drug-eluting beads (DC Bead®) for use in transarterial chemoembolization: a stability assessment.

PURPOSE: Evaluation of doxorubicin stability over time when stored into the DC Bead embolic agent, in various containers, which are used for the delivery of the doxorubicin-loaded beads to the patients for up to 14 days under refrigerated conditions. METHODS: The doxorubicin was loaded through the ionic exchange mechanism into the calibrated polyvinyl alcohol-based hydrogel beads (DC Bead), with the loading process carried out either in the original DC Bead glass vials or within a polypropylene plastic syringe. The loaded samples were eluted at given time points and the extracted doxorubicin was analysed by high-performance liquid chromatography for concentration and chromatographic area response purity. RESULTS: The variance on the doxorubicin concentration of the samples stored in the syringes under refrigerated conditions was less than 10% over the 14 days period. The chromatographic purity of doxorubicin eluted from the DC Bead in their primary glass vial packaging was measured at 99.7%. The dissolution test showed that the elution rate and amount recovered from samples stored in vials were statistically similar between Day 0 and Day 14. The chromatographic purity of the doxorubicin loaded into DC Bead in presence of non-ionic contrast medium was >99.0% for 7 days under refrigerated conditions. CONCLUSIONS: Doxorubicin-loaded DC Bead® are shown to have adequate physicochemical stability over a period of 14 days when stored in syringes or vials under refrigerated conditions for up to 14 days. The admixtures of doxorubicin-loaded beads with contrast medium are stable for up to 7 days under refrigerated conditions.

Evaluation of 30-days stability of morphine hydrochloride and clonidine at high and low concentrations in polypropylene syringes.

OBJECTIVES: Clonidine is an alpha-2 adrenoreceptor agonist and is frequently combined with opioids (ie, morphine hydrochloride (HCl)) for the management of chronic pain. In palliative care, the administration of clonidine and morphine HCl is recommended in case of tolerance effect. This study aimed to evaluate the physical and chemical stability of this admixture at high and low concentrations in 14 and 48 mL polypropylene syringes. METHODS: The stability of a low concentration admixture of clonidine (Catapressan 0.15 mg/mL, Boehringer Ingelheim, Germany) and morphine (morphine HCl 40 mg/mL, Sterop, Belgium) at 0.003 and 0.417 mg/mL, respectively, was evaluated by using five polypropylene syringes of 48 mL. The high concentration admixture consisted of 0.032 mg/mL clonidine and 4.286 mg/mL morphine HCl and was evaluated by using five polypropylene syringes of 14 mL. All syringes were stored for 30 days at 5°C±3°C. Periodic samples were visually and microscopically examined to observe any particle appearance or colour change. pH and absorbance at three wavelengths (350, 410 and 550 nm) were monitored. The concentrations were measured by ultra-high performance liquid chromatography-photodiode array detection. RESULTS: During the 30 days, there was no change in colour or appearance of opacity, turbidity or precipitation, and pH remained stable. The low and high concentration admixtures were considered chemically stable since the lower limit of the 90% CI remained superior to 90% of the initial concentration. Concentration measurements showed that the degradation rate was less than 1% over 10 days for each component in both admixtures. CONCLUSIONS: The admixture of clonidine and morphine HCl at low and high concentrations in polypropylene syringes appeared to be physically and chemically stable throughout the study period of 30 days at 5°C±3°C. In conclusion, the admixture can be prepared in advance under aseptic conditions by a centralised intravenous additive service in the pharmacy department.

An ultra-high-performance chromatography method to study the long term stability of gemcitabine in dose banding conditions.

Gemcitabine is an analogue of cytidine arabinoside, used alone or in combination chemotherapy to treat various type of cancer. The dose-banding of gemcitabine provides the opportunity to anticipate the preparation of this anticancer drug on condition of carrying out stability studies. The aim of this study is to develop and validate a stability-indicating ultra-high-performance Liquid Chromatography (UHPLC) method for measuring the concentration of gemcitabine and to evaluate its stability at standardised rounded doses in polyolefin bags. The UHPLC with photodiode array (PDA) detector method was developed and validated (linearity, precision, accuracy, limits of detection and quantification, robustness and degradation test). Thirty polyolefin bags of gemcitabine (1600 mg/292 ml (n = 10), 1800 mg/297 ml (n = 10) and 2000 mg/303 ml (n = 10)) were prepared under aseptic conditions and stored at 5 ± 3 °C and 23 ± 2 °C for 49 days. Physical stability tests were periodically performed: visual and microscopic inspection and optical densities. The chemical stability was evaluated through pH monitoring and chromatographic assays. The results confirm the stability of Gemcitabine at selected standardised rounded doses of 1600 mg, 1800 mg and 2000 mg in NaCl 0.9% polyolefin bags for at least 49 days at 5 ± 3 °C and 23 ± 2 °C, allowing in-advance preparation.

Physical and Chemical Stability of Pharmaceutical Preparation of Bumetanide and Scopolamine.

Death rattle, which could often be associated with a pulmonary fluid overload, occurs in 25% to 90% of dying patients. The co-administration of scopolamine (anticholinergic drug) and bumetanide (loop diuretic) could be considered in order to avoid unnecessary fluid overload at end-stage of life. The objective of this study was to investigate the physical and chemical stabilities of the admixture bumetanide and scopolamine in order to prepare them in advance by a centralized intravenous additive service in-hospital pharmacy. The stability of the lowest (LOW) concentration was evaluated on five polypropylene syringes containing the admixture bumetanide (Burinex, 2 mg/4 mL) and scopolamine (0.25 mg/mL) at 41.67 µg/mL and 5.21 µg/mL. The highest (HIGH) concentration with 125 µg/mL of bumetanide and 31.25 µg/mL of scopolamine was evaluated on five polypropylene syringes. All syringes were stored for 18 days at 5°C ± 3°C. Periodic samples were visually and microscopically examined to observe any particle appearance or color change. The pH and absorbance at 3 wavelengths (350 nm, 410 nm, and 550 nm) were monitored. The concentrations were measured by ultra-high performance liquid chromatography-photodiode array detection, using a newly developed method. During the 18 days of test, there was no change in color or appearance of opacity, turbidity, or precipitation, and the pH remained stable. Mean concentrations of bumetanide and scopolamine at LOW and HIGH concentrations after 18 days remained statistically unchanged. The lower limits of the 95% confidence intervals of both molecules at LOW and HIGH concentrations remained higher than a 90% threshold of concentration, indicating the mixture was chemically stable. Degradation rates of bumetanide and scopolamine content at LOW and HIGH concentrations should not exceed a maximum of 0.70% every 10 days. This study was the first to show that the admixture of bumetanide and scopolamine is physically and chemically stable at two concentrations used in a palliative-care unit. This combination available in ready-to-use polypropylene syringes presents numerous advantages for patient's comfort and safety.

Compounding Robots for Intravenous Therapy in European Countries: A Review in 2020.

A literature review was conducted in 2019 on the reconstitution of intravenous drugs. The following methods were identified: manual, semi-automatic, and automatic. A classification was carried out in three categories: automatic syringes, peristaltic pumps, and compounding doses robots. Data concerning the robots described in the previous review and possible robots that have appeared in the meantime were collected. The robots have been classified into 2 categories: with or without arms. The objective of the present review focuses on an updated review of the availability of compounding robots for intravenous therapy that are currently on the market.

Microwave Freeze-thaw Technique for Injectable Drugs: A Review Updated from 1980 to 2021.

The objective of this review was to collect information and results about the method of the microwave freeze-thaw treatment of injectable drugs and whether the method can support the development of Centralized Intravenous Admixtures Services. A systematic review of the scientific literature about injectable drug stability studies was performed. The data are presented in a table, which describes the name of the drug, producer, final concentration, temperature and time of freezing storage, type of microwave oven, thawing power, method of dosage, and the results after treatment or final long-term storage at 5°C ± 3°C. From 1980 to 2021, 60 drugs were studied by the microwave freeze-thaw treatment, and the results were presented in 49 publications. Forty papers were presented by 8 teams (2 to 18 by team). The temperatures of freezing storage varied from -70°C to -10°C, the time storage from 4 hours to 12 months, and the thaw from low to full power. Drug concentrations were mainly determined by high-performance liquid chromatography. Most of the 59 drugs were stable during and after treatment. Only three teams tested the long-term stability after the microwave freeze-thaw treatment, the first for ganciclovir after 7 days, the second for ceftizoxime after 30 days, and the third for 20 drugs after 11 to 70 days. This review can help Centralized Intravenous Additive Services take charge of the productions of ready-to-use injectable drugs.

Long-term physico-chemical stability of 5-fluorouracile at standardised rounded doses (SRD) in MyFuser® portable infusion pump.

Management of chemotherapies is a strategic issue for european healthcare. Dose-banding enables to reduce waiting time of patients in day care units and drug wastage. The aim of this study was to assess the stability of 5-Fluorouracile (5-FU) at standardised rounded doses of 4 and 5 g in MyFuser® portable infusion pump for in-advance preparation. Ten MyFuser® (4 and 5 gr 5-FU added to NaCl 0.9%) were prepared under aseptic conditions and stored at room temperature (23 ± 2 °C) for 28 days then at 30 °C for three days. Physical stability tests were periodically performed: visual and microscopic inspection, pH measurements and optical densities. The concentration of solutions was measured by High Performance Liquid Chromatography/UV detector. Results confirm the stability of 5-FU at selected SRD of 4 g and 5 g with NaCl 0.9% in MyFuser® for at least 28 days at room temperature and three days at 30 °C, allowing in-advance preparation.

Specification and Evaluation of Plasticizer Migration Simulants for Human Blood Products: A Delphi Study.

Potentially toxic plasticizers are commonly added to polyvinyl chloride medical devices for transfusion in order to improve their flexibility and workability. As the plasticizers are not chemically bonded to the PVC, they can be released into labile blood products (LBPs) during storage. Ideally, LBPs would be used in laboratory studies of plasticizer migration from the medical device. However, short supply (i.e., limited stocks of human blood in collection centres) has prompted the development of specific simulants for each type of LBP in the evaluation of new transfusion devices. We performed a Delphi study with a multidisciplinary panel of 24 experts. In the first (qualitative) phase, the panel developed consensus definitions of the specification criteria to be met by each migration simulant. Next, we reviewed the literature on techniques for simulating the migration of plasticizers into LBPs. A questionnaire was elaborated and sent out to the experts, and the replies were synthesized in order to obtain a consensus. The qualitative study established specifications for each biological matrix (whole blood, red blood cell concentrate, plasma, and platelet concentrate) and defined the criteria required for a suitable LBP simulant. Ten criteria were suggested: physical and chemical characteristics, opacity, form, stability, composition, ability to mimic a particular clinical situation, ease and safety of use, a simulant-plastic interaction correlated with blood, and compatibility with analytical methods. The questionnaire data revealed a consensus on the use of natural products (such as pig's blood) to mimic the four LBPs. Opinions diverged with regard to synthetic products. However, an isotonic solution and a rheological property modifier were considered to be of value in the design of synthetic simulants. Consensus reached by the Delphi group could be used as a database for the development of simulants used to assess the migration of plasticizers from PVC bags into LBPs.

Long-term stability of an infusion containing paracetamol, alizapride, ketorolac and tramadol in glass bottles at 5±3°C.

Background and objective: Infusion containing paracetamol, alizapride, ketorolac and tramadol is used after a general anaesthesia in order to limit pain, fever and nausea. Currently, these infusions are prepared according to demand in the anaesthesia unit, but the preparation in advance could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in glass bottles at 5°C ± 3 °C. Method: Five bottles of infusion were stored at 5°C ± 3 °C for 60 days. A visual and microscope inspection were performed periodically to observe any particle appearance or colour change. pH and absorbance at three wavelengths were measured. The concentrations were measured by ultra-high performance liquid chromatography - diode array detection. Results: Multiple verifications were performed during the first 35 days and no crystal, impurity or colour change were observed. At the next time point (42nd day), crystals were visible to the naked eye. pH and absorbance at 350 nm and 550 nm were stable. A slight increase in the absorbance at 410 nm was observed during the study, suggesting that a degradation product could be formed and absorb at this wavelength. The infusion was considered chemically stable while the lower one-sided prediction limit at 95% remains superior to 90% of the initial concentration. Concentration measurements demonstrated that ketorolac and alizapride remained stable in the infusion for 35 days. The stability of tramadol was 28 days. However, degradation of paracetamol was much faster given that concentration has fallen below 90% of the initial concentration after 7 days. Conclusion: Infusion of paracetamol, alizapride, ketorolac and tramadol remains stable for 7 days in glass bottles at 5°C ± 3 °C and could be prepared in advance with these storage conditions.

Long-term Physicochemical Stability of Concentrated Solutions of Isosorbide Dinitrate in Polypropylene Syringes for Administration in the Intensive Care Unit.

In order to avoid fluid overload, more concentrated drug solutions in intensive care units are commonly used. This study evaluated the physicochemical stability of concentrated solution of isosorbide dinitrate in polypropylene syringes during 28 days at 5°C ± 3°C with protection from light. Five syringes of 50 mL, containing 0.60 mg/mL of isosorbide dinitrate in sodium chloride 0.9% were prepared and stored at 5°C ± 3°C with protection from light during 28 days. Immediately after preparation and periodically during the storage, isosorbide dinitrate concentration was measured by an ultra-performance liquid chromatography. Spectrophotometric absorbance at different wavelengths, pH measurements, and microscopic observations were also performed. All solutions were physicochemically stable during the whole period storage at 5°C ± 3°C. No color change, turbidity, precipitation or opacity, significant pH variations, or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. The concentration of isosorbide dinitrate remained above 90% of the initial concentration during the 28 days of storage. Solutions of isosorbide dinitrate 0.60 mg/mL in syringe of sodium chloride 0.9 % injection can be considered physically and chemically stable for 28 days when stored in syringes at 5°C ± 3°C with protection from light and may be prepared in advance by a centralized intravenous additive service.

Long-term stability of tramadol chlorhydrate and metoclopramide hydrochloride in dextrose 5% polyolefin bag at 4 degrees C.

OBJECTIVES: Preparation of intravenous solution in advance could be efficient to improve quality assurance, security, time management, and cost saving of drug delivery. The purpose of this study was to investigate the stability of a mixture of tramadol chlorhydrate and metoclopramide hydrochloride in dextrose 5% polyolefin bags at 4 degrees C. METHODS: The stability of five bags of solution containing 100 mg tramadol and 10 mg metoclopramide per 100 mL dextrose 5% and stored at 4 degrees C was studied during 32 days and concentrations measured by high performance liquid chromatography-diode array detection. RESULTS: No degradation interference nor modification in retention times were observed throughout the study period. At day 32, tramadol concentration was 96.9% +/- 2.1 and metoclopramide 97.2% +/- 1.3 of the initial concentration. CONCLUSION: Based on a shelf-life of 90% residual potency, tramadol and metoclopramide were compatible and stable for at least 32 days at 4 degrees C and can be prepared in advance in a centralized intravenous additive service facility.

Long-term stability of 5-Fluorouracil in 0.9% sodium chloride after freezing, microwave thawing, and refrigeration.

OBJECTIVE: To investigate the stability of 5-fluorouracil diluted in 0.9% sodium chloride (normal saline [NS]) after freezing, microwave thawing, and storage for 28 days at 5°C ± 3°C. METHODS: Polyvinylchloride (PVC) infusion bags (n = 5) containing 5-fluorouracil 800 mg/100 mL were frozen for 79 days at -20°C. The bags were then thawed in a microwave oven and stored at 5°C ± 3°C for 28 days. The concentration of 5-fluorouracil was measured by high-performance liquid chromatography. Visual and microscopic inspections were performed and pH was measured periodically during storage. Solutions were considered stable if the lower limit of the 95% confidence interval of the concentration versus time profile remained greater than 90% of the initial concentration. RESULTS: No colour change or precipitation was observed in any of the solutions. Slight changes in pH were observed during refrigeration. 5-Fluorouracil solutions were stable during storage at 5°C ± 3°C for 28 days, as indicated by the results of high-performance liquid chromatography. CONCLUSION: 5-Fluorouracil 8 mg/mL in NS may be prepared in advance, frozen and stored in PVC bags, and thawed before use. The solutions remained stable after freezing at -20°C for 79 days followed by storage at 5°C ± 3°C for up to 28 days.

Long-term Physiochemical Stability of Concentrated Solutions of Salbutamol (Albuterol) in Polypropylene Syringes for Use in the Intensive Care Unit and in Obstetrics.

In order to avoid fluid overload, the use of more concentrated drug solutions in intensive care units and obstetrics is common. The objective of this study was to quantify the physicochemical stability of a concentrated solution of salbutamol (albuterol) in polypropylene syringes during 30 days of storage at 5°C ± 3°C with protection from light. Four 50-mL syringes containing 0.060mg/mL of salbutamol (albuterol) in 0.9% NaCl were prepared and stored at 5°C ± 3°C with protection from light during 30 days of storage. Immediately after preparation and periodically during the storage, salbutamol (albuterol) concentrations were measured by an ultra-performance liquid chromatography. Spectrophotometric absorbance at different wavelengths, pH measurement, and microscopic observations were also performed. All solutions were physicochemically stable during the entire period of storage at 5°C ± 3°C: no color change, turbidity, precipitation or opacity, significant pH variations, or optic densities were observed in the solutions. No crystals were seen by microscopic analysis. Concentrations of salbutamol remained stable during the storage period. Solutions of salbutamol (albuterol) 0.060 mg/mL in syringes of 0.9% NaCl are physically and chemically stable for at least 30 days when stored in syringes at 5°C ± 3°C with protection from light and may be prepared in advance by a centralized intravenous additive service.

Long-term Physicochemical Stability of Concentrated Solutions of Sodium Valproate in Polypropylene Syringes for Administration in the Intensive Care Unit.

In some situations, drug solutions in higher concentrations are used in intensive care units. The objective of this study was to evaluate the physicochemical stability of concentrated solutions of valproate sodium in polypropylene syringes during 30 days at 5°C ± 3°C. Five syringes of 40 mL containing 20 mg/mL of sodium valproate in 0.9% sodium chloride were prepared and stored at 5°C ± 3°C during 30 days. Immediately after preparation and periodically during the storage, valproate concentrations were measured by high-performance liquid chromatography. Spectrophotometric absorbance at different wavelengths, pH measurement, and microscopic observations were also performed. All solutions were physically stable during the study period storage at 5°C ± 3°C. No color change, turbidity, precipitation, or opacity at visual observation was noticed. No significant pH variations or optic densities were observed. No crystals were seen by microscopic analysis. Concentrations of valproate remained stable during the period of storage. Solutions of sodium valproate 20 mg/mL in syringes of 0.9% sodium chloride were physically and chemically stable for at least 30 days when stored in syringes at 5°C ± 3°C. These solutions may be prepared in advance by a centralized intravenous additive service.

Evaluation of the Physicochemical Stability of Amiodarone Hydrochloride in Syringes for the Intensive Care Unit.

In some emergency clinical situations, the injection of a more concentrated drug solution in the intensive care units is common. The purpose of this study was to evaluate the physicochemical stability of concentrated solutions of amiodarone hydrochloride in polypropylene syringes during 28 days of storage at 5°C ± 3°C, with protection from light. Five syringes of 50 mL, containing 25 mg/mL of amiodarone in dextrose 5%, were prepared and stored at 5°C ± 3°C with protection from light during 28 days. Immediately after preparation and periodically during the storage, amiodarone hydrochloride concentrations were measured by ultra-performance liquid chromatography. Spectrophotometric absorbance at different wavelengths, pH measurement, and microscopic observations were also performed. All solutions were physicochemically stable during the study period when stored at 5°C ± 3°C. No color change, turbidity, precipitation, opacity, significant pH variations, or optic densities were observed in the solutions. No crystals were seen by microscopic analysis. The concentration of amiodarone did not decrease during the 28 days of storage. Solutions of amiodarone 25 mg/mL in syringes of dextrose 5% are physically and chemically stable for at least 28 days when stored in syringes at 5°C ± 3°C with protection from light and may be prepared in advanced by a centralized intravenous additive service.

Long-term Physicochemical Stability of Concentrated Solutions of Noradrenaline Bitartrate in Polypropylene Syringes for Administration in the Intensive Care Unit.

Intensive care units use drug solutions within higher concentrations to avoid fluid overload. The purpose of this study was to evaluate the physicochemical stability of concentrated solutions of noradrenaline bitartrate in polypropylene syringes during 30 days of storage at 5°C ± 3°C. Five 50-mL syringes containing 0.240 mg/mL of noradrenaline bitartrate in 0.9% sodium chloride were prepared and stored at 5°C ± 3°C during 30 days. Immediately after preparation and periodically during the storage, noradrenaline concentrations were measured by high-performance liquid chromatography. Spectrophotometric absorbance at different wavelengths, pH measurement, and microscopic observations were also performed. The results showed that all solutions were physicochemically stable during the entire storage period at 5°C ± 3°C, and no color change, turbidity, precipitation, opacity, significant pH variations, nor optic densities were observed. Microscopic analysis was used to determine if there was any formation of crystals. The concentration of noradrenaline was not found to decrease during the 30 days of storage. Solutions of noradrenaline bitartrate 0.240 mg/mL in syringes of 0.9% sodium chloride were physically and chemically stable for at least 30 days when stored in syringes at 5°C ± 3°C and may be prepared in advanced by a centralized intravenous additive service.

Analysis of particulate exposure during continuous drug infusion in critically ill adult patients: a preliminary proof-of-concept in vitro study.

BACKGROUND: In critically ill patients, drug incompatibilities frequently occur because of the number of drugs to be administered through a limited number of infusion lines. These are among the main causes of particulate contamination. However, little data is available to quantify particle exposure during simultaneous IV-drug infusion. The objective of this study was to evaluate the particulate matter potentially administered to critically ill patients. METHODS: The particulate matter (between 1 µm and 30 mm) of infused therapies used in ICUs for patients suffering from either septic shock or acute respiratory distress syndrome was measured in vitro over 6 h using a dynamic image analysis device, so that both overall particulate contamination and particle sizes could be determined. Data is presented according to the recommendations of the European Pharmacopoeia (≥ 10 and 25 µm). RESULTS: For the six experimental procedures (continuous infusion of norepinephrine, midazolam, sufentanil, heparin, 5% glucose, binary parenteral nutrition and discontinuous administrations of omeprazole, piperacillin/tazobactam and fluconazole), the overall number of particles over the 6-h infusion period was 8256 [5013; 15,044]. The collected values for the number of particles ≥ 10 and 25 µm were 281 [118; 526] and 19 [7; 96] respectively. Our results showed that discontinuous administrations of drugs led to disturbances in particulate contamination. CONCLUSIONS: This work indicates the amount of particulate matter potentially administered to critically ill adult patients. Particulate contamination appears lower than previous measurements performed during multidrug IV therapies in children.