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Automated compounding systems appeared on the market during these last 15 years as an alternative for manual compounding of intravenous (IVD) drugs. A literature review was conducted on reconstitution of IVD. 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. The number of compounding robots is increasing. A table describes the different features of each device. The ampuls cannot be supported by these robots. Large doses vials improve the time of reconstitution compared to current dosage vials. Advantages of automated preparation are: higher consistency of process and products, higher accuracy of products, Integrated digitized processing, precise, complete documentation, reduced effort and wrist injuries, reduced personnel requirement, increased worker satisfaction. Disadvantages of automated preparation are: risk of failure/down time, dependency on power supply, software (updates), high investment costs/high maintenance costs, specialized personnel with additional training, decreased worker satisfaction (early adopter), complexity when products are switched or added, potential for new errors. This review allows the potential user to know the current availability on the market.

Background Cefotaxime sodium is an antibiotic used to treat severe infections such as in intensive care units (ICUs). The recommended dose of cefotaxime sodium can vary from 3 grams (g) to 24 g per day and publications have demonstrated that continuous administration of cefotaxime sodium is the preferred mode of administration. In ICUs, a minimum volume is used for patients requiring fluid restriction, leading to high concentrations of cefotaxime sodium. The objective was to study the stability of cefotaxime sodium solutions at 83.3 mg/mL and 125 mg/mL, diluted in 0.9 % sodium chloride (0.9 % NaCl) or in 5 % glucose (G5 %), stored in polypropylene syringes, after the preparation and after a 6-hour and a 12-hour storage at 20–25 °C. Methods Three syringes for each condition were prepared. At each time of the analysis, three samples for each syringe were prepared and analysed by high performance liquid chromatography (HPLC) coupled to a photodiode array detector. The method was validated according to the International Conference on Harmonisation Q2(R1). Physical stability was evaluated by visual and subvisual inspection (turbidimetry by UV spectrophotometry at 350, 410 and 550 nm as recommended by the European Consensus Conference). pH and osmolality values were measured at each time of the analysis. Results For each solvent, cefotaxime sodium solutions at 83.3 mg/mL and 125 mg/mL retained more than 90 % of the initial concentration after 12 hours. During the stability study, pH values decreased slightly, the intensity of the yellow colour increased and values of absorbance increased progressively for each wavelength and each condition. An additional peak with a relative retention of 3.01 was also observed after the forced degradation gradually increased up to 4.01 % and 3.17 % of the total of surface area of the peaks present on the chromatogram after 12 hours in 0.9 % NaCl and in G5 % respectively. Conclusions In view of the results and despite the fact that solutions retained more than 90 % of the initial concentration after HPLC analysis, we propose to limit the stability of cefotaxime sodium in 0.9 % NaCl and G5 % at 83.3 and 125 mg/mL at 6 hours. These stability data of highly concentrated solutions provide an additional knowledge to assist ICUs in daily practice. This work also demonstrates that highly concentrated cefotaxime sodium solutions are physically unstable after a 6-hour storage and cannot be administered as a daily infusion.

Background Urea is recommended in the 2nd line treatment in moderate to severe hyponatraemia induced by syndrome of inappropriate antidiuretic hormone secretion (SIADH), when water restriction is insufficient. A posology of 0.25–0.5 g/kg daily is suggested. A usual but inadequate urea oral preparation, i. e. 10 g urea powder dissolved in 100 mL water before use, was classically compounded. Therefore the pharmacy has developed a 0.5 g/mL urea oral liquid solution in InOrpha ® with better organoleptic characteristics to improve treatment adherence and reduce the preparation time. The aim of this study was to determine physicochemical and microbiological stability of the urea oral liquid solution in order to establish a shelf life of the preparation. Methods The 0.5 g/mL urea solution was compounded using urea powder in a commercial suspending vehicle: Inorpha ® . A validated high-performance liquid chromatographic (HPLC) method with UV detection was performed for the assay of urea. The preparations were packaged in amber glass bottles and stored at fridge (5 °C±3 °C) or at room temperature (24 °C±1 °C). The physicochemical (urea concentration, macroscopic change) and microbiological stability of the preparation was tested over 90 days. Urea concentration measurement at day 0 was considered as the reference value (100 % stability) and urea concentration in subsequent samples greater than 90 % were definite stable without macroscopic changes. Results The developed HPLC-UV method was validated in terms of linearity, specificity, accuracy and fidelity (less than 5 % for relative standard deviation and relative error). After 90 days, no microbial growth was noted and urea concentrations were always higher than 90 % of the initial concentration. Macroscopic changes were observed for the samples stored at fridge (5 °C+/− 3 °C) with massive crystallization of urea solution. Conclusions Although, all the preparations retain more than 95 % of the initial concentration after 90 days in all storage conditions, macroscopic change and pH change (more than 1 unit after 15 days at room temperature) have to be taken into account. The 0.5 g/mL urea oral liquid solution in InOrpha ® remains stable for 15 days at room temperature (24 °C±1 °C) in amber glass bottles.

Background Propofol and remifentanil often need to be co-administered via the same intravenous catheter line, which predisposes to potential compatibility issues. Our aim was to determine and compare the emulsion stability of three propofol formulations, two with medium chain triglycerides and one with long chain triglycerides, when administered together with remifentanil hydrochloride. Methods Remifentanil hydrochloride ( Ultiva ® ) 50 µg/mL was mixed with two concentrations (10 and 20 mg/mL) of each propofol formulation in mixing ratios 10+1, 20+1, 1+1 and 1+20. Emulsion stability was assessed immediately after mixing and 4 hours later by measurements of pH, mean droplet diameter, polydispersity index, and calculating percentage of fat residing in globules>5 µm (PFAT5). Results High PFAT5 values were observed in certain mixing ratios. The correlation between elevated PFAT5 and high propofol concentration (20 mg/mL), when remifentanil was in abundance and for long contact time indicated that these factors influenced the stability of the propofol emulsions. Conclusions Stability differences between the propofol formulations were identified under extreme test conditions. Co-administration of remifentanil and propofol in the same i.v. line is safe when propofol is in abundance. Caution is advised when remifentanil is present in equal parts or in abundance when co-administered with propofol 20 mg/mL.

Background The preparation of many drugs intended for parenteral administration is centralized in the pharmacy of healthcare institutions. However, no data are available describing the range of drugs with centralized preparation. The objective was to establish a profile of centralization practices for the preparation of non-hazardous drug doses in the pharmacy departments of Quebec healthcare institutions. Methods For this cross-sectional descriptive study, an e-mail survey was distributed in March 2017 to the directors of the pharmacy departments of Quebec healthcare institutions. Respondents were asked to estimate the percentage of parenteral drug doses that were prepared centrally in the pharmacy, the name of each drug prepared this way, the criteria used to select drugs for central preparation, and the barriers to centralizing preparation of drug doses. Only descriptive statistical analyses were performed. Results Of the 30 directors of pharmacy departments invited to participate, 27 (90 %) responded, representing a total of 40 Quebec healthcare facilities. Overall, 232 individual drugs were centrally prepared in one or more of these facilities, for an overall median of 22 drugs per facility (min: 1, max: 101). Conclusions This is the first survey in Quebec and indeed all of Canada to identify the many medications that are centrally prepared in hospital pharmacies. The survey showed that the selection of drugs for central preparation differed widely across facilities. It would be desirable for pharmacy departments in this province to collaborate on standardizing practices for central preparations.

This opinion paper describes the discussions of the attendees of the last GERPAC European conference workshop on the question of chemical stability and container-content interactions. Pharmacists discussed the steps to implement to carry out those studies that are particulary important to asses the quality of the compounded preparations in hospital pharmacies.