Long-term stability of ready-to-use 1-mg/mL midazolam solution

2020 ◽  
Vol 77 (9) ◽  
pp. 681-689
Author(s):  
Sixtine Gilliot ◽  
Morgane Masse ◽  
Frédéric Feutry ◽  
Christine Barthélémy ◽  
Bertrand Décaudin ◽  
...  
Keyword(s):  
High Performance ◽  
Detection Method ◽  
Degradation Products ◽  
Storage Conditions ◽  
Target Concentration ◽  
Long Term Stability ◽  
Ph Values ◽  
Particle Contamination ◽  
The Stability

Abstract Purpose Midazolam is a benzodiazepine derivative commonly used in intensive care units to control sedation. Its use requires dilution of a 5-mg/mL commercial solution to a target concentration of 1 mg/mL. A study was conducted to evaluate the stability of diluted ready-to-use 1-mg/mL midazolam solutions over 365 days when stored in cyclic olefin copolymer vials or polypropylene syringes. Methods A specific stability-indicating high-performance liquid chromatography coupled with UV detection method was developed for midazolam hydrochloride and validated for selectivity, linearity, sensitivity, precision, and accuracy. Three storage conditions were tested: –20°C ± 5°C, 5°C ± 3°C, and 25°C ± 2°C at 60% ± 5% relative humidity. Half of the vials were stored upside down to test for the absence of interaction between midazolam and the stopper. Particle contamination, sterility, and pH were assessed. Results The limit of stability was set at 90% of the initial concentration. After 1 year’s storage at –20°C and 5°C, concentrations remained superior to 90% under all storage conditions. At 25°C, stability was maintained up to day 90 in syringes (mean [SD], 92.71% [1.43%]) and to day 180 in upright and upside-down vials (92.12% [0.15%] and 91.57% [0.15%], respectively). No degradation products were apparent, no variations in pH values were detected, and containers retained their sterility and conformity with regard to any specific contamination during the study. Conclusion The evaluated 1-mg/mL midazolam solution was stable over a 1-year period when stored at a refrigerated (5°C) or frozen (–20°C) temperature in both vials and syringes; with storage at 25°C, the stability duration was lower. The preparation of ready-to-use midazolam solutions by a hospital pharmacy is compatible with clinical practice and could help to decrease risks inherent in dilution in care units.

scholarly journals The effect of concentration, reconstitution solution and pH on the stability of a remifentanil hydrochloride and propofol admixture for simultaneous co-infusion

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Emily Henkel ◽  
Rebecca Vella ◽  
Kieran Behan ◽  
David Austin ◽  
Peter Kruger ◽  
...  
Keyword(s):  
Sodium Bicarbonate ◽  
High Performance ◽  
Saline Solution ◽  
Degradation Products ◽  
Sodium Bicarbonate Solution ◽  
Ultrapure Water ◽  
Long Term Stability ◽  
Anaesthetic Agents ◽  
The Stability

Abstract Background There are scenarios where pre-mixing and infusing analgesic and anaesthetic agents as a single intravenous (IV) solution is highly desirable; however, it is important to ensure the agents are compatible when mixed. As such, the long-term stability of a remifentanil-propofol mixture, and means of improving this, were assessed across a range of remifentanil concentrations, diluents, and time points. Methods Remifentanil was reconstituted with ultrapure water, 0.9% saline, 20% saline, or 8.4% sodium bicarbonate solution (the latter two chosen for their pH characteristics, rather than their use in pharmaceutical reconstitution) and then mixed with propofol (1%) or further diluted with water to derive concentrations of 10–50 μg mL− 1. Remifentanil and propofol concentrations were determined initially and then periodically for up to 24 h using high performance liquid chromatography (HPLC). Mass spectrometry (MS) was used to detect degradation products in solutions containing 30 μg mL− 1 of remifentanil. Statistical analysis was performed using ANOVA and Student’s t-test, with a significance value of 0.05. Results Isolated remifentanil (pH < 4) and propofol (pH 7.35) did not degrade significantly when reconstituted with water or saline solution over 24 h, while remifentanil reconstituted with sodium bicarbonate degraded significantly (P < 0.001, pH 8.65). Mixing with propofol substantially increased the pH of the mixture and resulted in significant remifentanil degradation for all reconstitution solutions used, while propofol remained stable (pH 6.50). The amount of degradation product detected in samples containing isolated remifentanil and a mixture of the drugs was proportional to the remifentanil degradation observed. Conclusions Remifentanil stability is affected by both the reconstitution solution used and when mixed with propofol, with pH appearing to be a contributing factor to degradation. If the pH of the solution and concentration of remifentanil are correctly controlled, e.g. through the use of a more acidic diluent, an admixture of remifentanil and propofol may be useful clinically.

scholarly journals Long-Term Stability Comparison between an Original and a Generic Version of Piperacillin/Tazobactam in Dextrose 5 % Infusion Polyolefin Bags at 5 ± 3 °C after Microwave Freeze-Thaw Treatment

2018 ◽  
Vol 3 (3) ◽  
pp. 143-151
Author(s):  
Sophie Huvelle ◽  
Marie Godet ◽  
Laurence Galanti ◽  
Mélanie Closset ◽  
Benoît Bihin ◽  
...  
Keyword(s):  
Generic Version ◽  
Generic Product ◽  
Brand Name ◽  
Term Stability ◽  
Long Term Stability ◽  
Ph Values ◽  
Lower Confidence ◽  
The Stability ◽  
Aseptic Conditions

AbstractBackgroundPiperacillin-Tazobactam is frequently infused in hospitals. The use of a generic version was considered after the out of stock of the brand name Tazocin®. The stability of 4 g of Tazocin®in 120 mL of dextrose 5 % (D5) was demonstrated during 35 days at 5 °C ± 3 °C after freezing (−20 °C) and microwave thawing (FMT). The aim of the study was to investigate and compare the long-term stability of Tazocin®and a generic product in the same conditions.MethodsFive polyolefin bags of 4 g of Piperacillin/Tazobactam®Sandoz and 5 bags of 4 g of Tazocin®were prepared under aseptic conditions in 120 mL of D5 and stored 3 months at 20 °C then thawed and stored 58 days at 5 ± 3 °C.Spectrophotometric absorbance at different wavelengths, pH measurement, visual and microscopic observations were also performed.The concentrations were measured by HPLC, at 211 nm for tazobactam and 230 nm for piperacilline.ResultsNo significant change in pH values or optic densities, no crystals were detected. The lower confidence limit at 95 % of the concentration for the solutions remains superior to 90 % of the initial concentration until 58 days of storage at 5 ± 3 °C.ConclusionUnder these conditions, 4 g/120 mL of Piperacillin/Tazobactam®Sandoz or Tazocin®in D5 infusion in polyolefin bags remains stable at least for 58 days at 5 ± 3 °C after FMT

scholarly journals Long-Term Stability of Lorazepam in Sodium Chloride 0.9% Stored at Different Temperatures in Different Containers

2019 ◽  
Vol 55 (3) ◽  
pp. 188-192
Author(s):  
M. L. Colsoul ◽  
A. Breuer ◽  
N. Goderniaux ◽  
J. D. Hecq ◽  
L. Soumoy ◽  
...  
Keyword(s):  
Time Management ◽  
High Performance ◽  
Room Temperature ◽  
Color Change ◽  
Storage Period ◽  
Term Stability ◽  
Long Term Stability ◽  
Glass Bottles ◽  
The Stability

Background and Objective: Infusion containing lorazepam is used by geriatric department to limit anxiety disorders in the elderly. Currently, these infusions are prepared according to demand by the nursing staff, but the preparation in advance in a centralized service could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in polypropylene syringes stored at 5 ± 3°C. Then, results obtained were compared with stability data of lorazepam in syringes stored at room temperature, glass bottles at 5 ± 3°C, and glass bottles at room temperature. Method: Eight syringes and 6 bottles of infusion were prepared by diluting 1 mL lorazepam 4 mg in 23 mL of NaCl 0.9% under aseptic conditions. Five syringes and 3 bottles were stored at 5 ± 3°C and 3 syringes and 3 bottles were stored at room temperature for 30 days. During the storage period, particle appearance or color change were periodically checked by visual and microscope inspection. Turbidity was assessed by measurements of optical density (OD) at 3 wavelengths (350 nm, 410 nm, 550 nm). The stability of pH was also evaluated. The lorazepam concentrations were measured at each time point by high-performance liquid chromatography with ultraviolet detector at 220 nm. Results: Solutions were physically unstable in syringes at 5 ± 3°C after 4 days: crystals and a drop of OD at 350 nm were observed. However, pH was stable. After 2 days, solutions were considered as chemically unstable because a loss of lorazepam concentration higher than 10% was noticed: the lower 1-sided confidence limit at 95% was below 90% of the initial concentration. To assess temperature and polypropylene influence, results were compared with those obtained for syringes at room temperature and bottles at 5 ± 3°C and room temperature. Precipitation, drop of OD at 350 nm, and chemical instability were observed in all conditions. Conclusion: Solutions of lorazepam were unstable after 2 days in syringes at 5 ± 3°C. Preparation in advance appears, therefore, not possible for the clinical use. Storage conditions (temperature and form) do not improve the stability.

scholarly journals Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Brittany K. Chavez ◽  
Cyrus D. Agarabi ◽  
Erik K. Read ◽  
Michael T. Boyne II ◽  
Mansoor A. Khan ◽  
...  
Keyword(s):  
High Performance ◽  
Storage Conditions ◽  
Size Exclusion ◽  
Worst Case ◽  
Long Term Storage ◽  
Improved Stability ◽  
Bioreactor System ◽  
The Stability ◽  
Storage Buffer

Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potential storage buffer due to significant visible precipitate formation. An additional 24full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Thus, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules.

Long-term stability of ganciclovir in polypropylene containers at room temperature

2017 ◽  
Vol 25 (2) ◽  
pp. 303-308 ◽  
Author(s):  
Nicolas Guichard ◽  
Pascal Bonnabry ◽  
Serge Rudaz ◽  
Sandrine Fleury-Souverain
Keyword(s):  
High Performance ◽  
Physical Stability ◽  
Significant Loss ◽  
Stability Indicating ◽  
Long Term Stability ◽  
Stability Indicating Method ◽  
All Solutions ◽  
Different Temperatures ◽  
The Stability

Purpose Ganciclovir is increasingly provided by hospital pharmacy production unit in a ready-to-use form, in order to improve the safety of healthcare workers and the efficiency of the organisation. The objective of this study was to develop a stability-indicating method to assay ganciclovir and determine the stability of ganciclovir in syringes (5 mg/mL) and infusion bags (0.25 and 5 mg/mL) at two different temperatures. Method Ganciclovir solutions (0.25 mg/mL and 5 mg/mL) in 0.9% sodium chloride were prepared in 50 mL polypropylene syringes or 100 mL polypropylene infusion bags and stored at 2–8℃ and 23–27℃. The chemical stability was measured using a stability-indicating Ultra High Performance Liquid Chromatography coupled to mass spectrometry method. Physical stability was assessed by visual inspection. Results No significant loss of ganciclovir under any of the tested conditions was observed in this study. All solutions remained clear through the study period. Conclusion All tested formulations remained stable for at least 185 days independently of container type, temperature or concentration studied.

scholarly journals Isolation and Thermal Stabilization of Bacteriocin Nisin Derived from Whey for Antimicrobial Modifications of Polymers

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Pavlina Holcapkova ◽  
Zuzana Kolarova Raskova ◽  
Martina Hrabalikova ◽  
Alexandra Salakova ◽  
Jan Drbohlav ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Polyethylene Glycol ◽  
High Performance ◽  
Thermal Stabilization ◽  
Nisin Production ◽  
Long Term Stability ◽  
Long Term Storage ◽  
The Stability ◽  
Term Storage

This work describes novel alternative for extraction of bacteriocin nisin from a whey fermentation media and its stabilization by using polyethylene glycol as matrix with high practical applicability. This product was compared with commercially available nisin product stabilized by sodium chloride and nisin extracted and stabilized by using ammonium sulfate and polysorbate 80. The stability of samples was tested by means of long-term storage at −18, 4, 25, and 55°C up to 165 days. The nisin content in the samples was determined by high-performance liquid chromatography and electrophoresis. In addition, effect of whey fortification with lactose on nisin production and antibacterial activity studied against Staphylococcus aureus was tested. Results show that stabilization by polyethylene glycol provides enhanced nisin activity at 55°C after 14 days and long-term stability at 25°C with keeping antibacterial activity.

scholarly journals Physicochemical Stability of Reconstituted Decitabine (Dacogen®) Solutions and Ready-to-Administer Infusion Bags when Stored Refrigerated or Frozen

2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Sun Hee Kim ◽  
Rita Marina Heeb ◽  
Irene Krämer
Keyword(s):  
High Performance ◽  
Degradation Products ◽  
Reversed Phase ◽  
Photodiode Array Detection ◽  
Ph Values ◽  
Physicochemical Stability ◽  
Colour Changes ◽  
Photodiode Array ◽  
Array Detection ◽  
The Stability

AbstractBackgroundProfound knowledge about the physicochemical stability is necessary in order to determine the “beyond-use-dates” of ready-to-administer preparations after reconstitution and dilution. This is especially true for unstable azanucleoside drugs like decitabine. The aim of this study was to determine the physicochemical stability of decitabine after reconstitution and dilution of DacogenMethodsTo determine the stability of frozen DacogenTo determine the stability of reconstituted DacogenDiluted DacogenDecitabine concentrations were determined at 0, 5, 8, 12, 24 and 48 hours after preparation. The pH-values were determined at 0, 8, 24 and 48 hours. Each sample was assayed by a validated stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay with photodiode array detection.ResultsWhen test solutions of reconstituted DacogenIn reconstituted test solutions in glass vials and in diluted test solutions in infusion bags stored under refrigeration decitabine concentrations remained above 90 % of the initial concentration for 12 hours and 24 hours, respectively. Several peaks of degradation products were observed which explicitly increased over time.In all test solutions the pH-values amounted to pH 7 and remained unchanged. No particulate matter and no colour changes were observed over the test period.ConclusionsReconstituted decitabine solution (Dacogen

The Stability of the WHO Reference Thromboplastin NIBS & C 67/40

1979 ◽  
Vol 42 (04) ◽  
pp. 1135-1140 ◽  
Author(s):  
G I C Ingram
Keyword(s):  
Human Brain ◽  
Collaborative Study ◽  
Calibration Constant ◽  
Long Term Stability ◽  
Freeze Dried ◽  
Show Evidence ◽  
Human Material ◽  
Reference Preparation ◽  
The Stability

SummaryThe International Reference Preparation of human brain thromboplastin coded 67/40 has been thought to show evidence of instability. The evidence is discussed and is not thought to be strong; but it is suggested that it would be wise to replace 67/40 with a new preparation of human brain, both for this reason and because 67/40 is in a form (like Thrombotest) in which few workers seem to use human brain. A �plain� preparation would be more appropriate; and a freeze-dried sample of BCT is recommended as the successor preparation. The opportunity should be taken also to replace the corresponding ox and rabbit preparations. In the collaborative study which would be required it would then be desirable to test in parallel the three old and the three new preparations. The relative sensitivities of the old preparations could be compared with those found in earlier studies to obtain further evidence on the stability of 67/40; if stability were confirmed, the new preparations should be calibrated against it, but if not, the new human material should receive a calibration constant of 1.0 and the new ox and rabbit materials calibrated against that.The types of evidence available for monitoring the long-term stability of a thromboplastin are discussed.

scholarly journals Using MoS2/Fe3O4 as Ion-Electron Transduction Layer to Manufacture All-Solid-State Ion-Selective Electrode for Determination of Serum Potassium

Chemosensors ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 155
Author(s):  
Yan Su ◽  
Ting Liu ◽  
Caiqiao Song ◽  
Aiqiao Fan ◽  
Nan Zhu ◽  
...  
Keyword(s):  
High Performance ◽  
Accurate Determination ◽  
Water Layer ◽  
Ion Selective Electrode ◽  
Potential Response ◽  
Selective Electrode ◽  
Response Measurement ◽  
Long Term Stability

As an essential electrolyte for the human body, the potassium ion (K+) plays many physiological roles in living cells, so the rapid and accurate determination of serum K+ is of great significance. In this work, we developed a solid-contact ion-selective electrode (SC-ISE) using MoS2/Fe3O4 composites as the ion-to-electron transducer to determine serum K+. The potential response measurement of MoS2/Fe3O4/K+-ISE shows a Nernst response by a slope of 55.2 ± 0.1 mV/decade and a low detection limit of 6.3 × 10−6 M. The proposed electrode exhibits outstanding resistance to the interference of O2, CO2, light, and water layer formation. Remarkably, it also presents a high performance in potential reproducibility and long-term stability.

High-performance humidity sensors from Ni(SO4)0.3(OH)1.4 nanobelts

Nanoscale ◽  
2014 ◽  
Vol 6 (12) ◽  
pp. 6521-6525 ◽  
Author(s):  
Ming Zhuo ◽  
Yuejiao Chen ◽  
Tao Fu ◽  
Haonan Zhang ◽  
Zhi Xu ◽  
...  
Keyword(s):  
High Performance ◽  
Humidity Sensor ◽  
High Sensitivity ◽  
Fast Response ◽  
Humidity Sensors ◽  
Term Stability ◽  
Long Term Stability

Ni(SO4)0.3(OH)1.4 nanobelts are utilized in a humidity sensor by a facile method. The nanobelt based sensor shows a high sensitivity, fast response and long-term stability in the sensing process.

Sign in / Sign up

Export Citation Format

Share Document