The use of continuous infusion to improve the therapeutic efficacy of time-dependent antibiotics has been demonstrated. There is still a lack of data to safely perform these continuous infusions. The objectives in this study were to evaluate the stability by using stability-indicating methods (High-Performance Liquid Chromatography) of 16 antibiotics in concentrated solutions, especially for administration in intensive care units and solutions in elastomeric diffusers at 37 °C for outpatient parenteral antimicrobial therapy. The solutions were considered stable if the percentage of the drug was ≥90%, and the colour and clearness remained unchanged. In syringes, the stability data vary from 4 to 8 h (h) for meropenem in Dextrose 5% (D5W) and Normal Saline (NS), respectively, 6 h for cefotaxime, 12 h for cefoxitin, and 24 h for aztreonam, cefazolin, cefepime, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam in NS and D5W, and in water for injection for cloxacillin. A stability period of 48 h has been validated for vancomycin (D5W), aztreonam, and piperacillin/tazobactam. Cefoxitin, cefazolin, cefepime, cefotaxime, cloxacillin, and piperacillin are unstable for diffuser administration. In diffusers, stability times vary from 6 h for cefiderocol, 8 h for ceftazidime, 12 h for ceftazidime/avibactam and ceftolozane/tazobactam (NS), 24 h for temocillin (NS) and piperacillin/tazobactam (D5W), up to 48 h for aztreonam and vancomycin. Solutions stored at 37 °C are less stable and allow the administration of seven antibiotics using diffusers.

Objectives Opioid-free anaesthesia is a treatment strategy of pain management based on the use of drugs such as lidocaine, ketamine and dexmedetomidine that do not interact significantly with opioid receptors. In particular, these drugs are used by anaesthesiologists to ensure adequate levels of analgesia during surgical procedures for burn patients such as daily wound dressings and graft surgeries. Furthermore, for hypothermia prevention and wound-healing purposes, ambient temperature must be kept high for these patients, usually between 27°C and 30°C. To facilitate the use of this technique, clinicians want to mix lidocaine and ketamine in the same syringe. No stability data is available to determine the feasibility of this admixture and at this temperature. The objective was to study the physicochemical stability of lidocaine 20 mg/mL with ketamine 2.5 mg/mL diluted with 0.9% sodium chloride (0.9% NaCl) stored at 28°C in polypropylene syringe for 48 hours. Methods Physical stability was evaluated by visual examination and by measuring turbidity with a spectrophotometer. Chemical stability was determined after preparation and after 6, 24 and 48 hours of conservation with a high performance liquid chromatography and pH measurements. The method was validated according to International Conference on Harmonisation Q2(R1) guidelines. results Both lidocaine (99.98%±1.44%) and ketamine (100.70%±0.95%) retained more than 95% of their initial concentration after 48 hours storage. pH measurements remained stable over the course of the study (less than 0.21 point of variation). No signs of physical instability were observed after visual and subvisual inspections. Conclusions The physicochemical stability of lidocaine 20 mg/mL and ketamine 2.5 mg/mL diluted with 0.9% NaCl in a polypropylene syringe stored at 28°C protected from light was demonstrated for 48 hours. This infusion technique is therefore feasible from a pharmaceutical point of view in burn-unit settings.

Introduction: In our centralized unit for the preparation of anticancer drugs, quality control is carried out by flow injection analysis (FIA) with detection by photodiode array detector. Criteria of concentration acceptance were established with ±10% of the theoretical concentration. The infusions were prepared with polyolefin infusions bags (Easyflex). However, due to an Easyflex shortage, Viaflo infusion bags were used and cyclophosphamide (CPM) concentrations showed a 10% increase despite a similar manufacturing process. The objectives of this work were to study the influence of different containers on CPM concentrations measured by FIA and to investigate the origin of this artificial increase in concentration. Methods: Thirty infusions were prepared using 3 different infusion bags: Viaflo multilayer container, Ecoflac, low-density polyethylene, and Easyflex polyolefin bags. Vials of CPM 1 g were reconstituted with 50 mL of 0.9% sodium chloride. CPM was injected into 0.9% sodium chloride 250-mL infusion bags. Then 1 mL samples were withdrawn to be analyzed by FIA, to determine CPM concentrations (ultraviolet detection at 205 nm). Results: Mean CPM concentration values (n = 10) were 3.52 mg/mL for Viaflo infusions, 3.12 mg/mL for Ecoflac infusions, and 3.16 mg/mL for Easyflex infusions. CPM concentrations were higher in Viaflo infusion bags. This difference could be explained by ε-caprolactam, a component released by the multilayer infusion bag. Conclusion: Viaflo infusion bags disturb outcomes of CPM dosage with a concentration artificially increased by about 10%. The FIA method cannot be used to quantify CPM at this concentration and at wavelength 205 nm.

ObjectivesIn intensive care units, the mixing of injectable drugs via Y-site administration is often necessary. However, some mixtures can lead to physical incompatibility or chemical instability. To assist healthcare professionals, several databases such as Stabilis compile compatibility and stability data. The objectives of this study were to update the online database Stabilis by adding physical compatibility data to the website and to characterise the incompatibility data already present in the database by specifying the phenomenon at the origin of the incompatibility and its time of occurrence.MethodsBibliographic sources referenced in Stabilis were evaluated using several criteria. After the evaluation, studies were rejected or the data they contain were added to the database. Data entries contained the following information: name of the two injectable drugs involved in the mixture and their concentration if available, the dilution solvent and the phenomenon at the origin of the incompatibility and its time of occurrence for incompatibility data. Three functions of the website were modified, including the ‘Y-site compatibility table’ function, which allows creation of customised compatibility tables.ResultsA total of 1184 bibliographic sources were evaluated, 77.3% (n=915) of which were scientific articles, 20.5% (n=243) were Summaries of Product Characteristics and 2.2% (n=26) were communications in a pharmaceutical congress. After evaluation, 28.9% (n=342) of the sources were rejected. From the 71.1% (n=842) sources selected, 8073 (70.2%) compatibility data entries and 3433 incompatibility data entries (29.8%) were made. With the addition of these data, the database contained compatibility and incompatibility data for 431 injectable drugs.ConclusionsSince the update, the ‘Y-site compatibility table’ function has seen its traffic increased by about 66% (∼1500 tables per month compared with ∼2500 tables per month). Stabilis is now more complete to offer significant help to healthcare professionals with their problems of drug stability and compatibility.