Band 7, Heft 1

Objectives Fungal keratitis is a rare but severe cause of infectious keratitis and can lead to blindness. To cure fungal keratitis, antifungal like voriconazole eye drops must be immediately administered. As no brand is available on the market, voriconazole ophthalmic solution is compounded in hospital pharmacies using voriconazole powder for intravenous infusion. The aims of our study were to both assess the physico-chemical and microbiological stability of eye drop solutions stored at +2 to 8 °C. Two different High-Density-Polyethylene (HDPE) eye drop dispensing containers were assessed, one with a sterility preserving cap Novelia ® (Nemera) and the other without sterility preserving cap both provided by CAT laboratory. In addition microbiological quality was assessed during 15 days simulated patient use. Methods Multiple batches of voriconazole 10 mg/mL eye drops were prepared and stored at +2 to 8 °C to study their stability over 90 days. All analyses were performed in triplicate. Physical stability was determined, pH determination, osmolarity measurement, and a particle count test was also performed. A high performance liquid chromatography (HPLC-UV) stability indicating method was used to determine chemical stability of the ophthalmic solution over 90 days of storage. For microbiological stability, a sterility test was performed using closed membrane filtration method (Steritest ® , Merck Millipore) at D0, D90 and D90+15 days after simulated administration of eye drops (D90+15). Results For both containers, no variation of visual aspect, pH, osmolality, particle count and final concentration were observed. No microbiological growth was observed after 90 days of storage. At the end of the simulated administration period (D+15), unconstant microbiological growth was only observed in HDPE vials without sterility preserving cap, whereas HDPE vials with a sterility preserving cap Novelia ® (Nemera) remained sterile. Conclusions Voriconazole 10 mg/mL ophtalmic solution was stable during 90 days at +2 to 8 °C in lightproof HDPE vials without sterility preserving cap and HDPE vials with a sterility preserving cap Novelia ® (Nemera). However, vials with classical cap which are not airtight systems, may microbiologically contaminated during patient’s use than vials with Novelia ® cap thanks to their innovative valve system.

Objectives The compounding and administration of hazardous drugs present a potential risk to healthcare worker and patient safety. This study sought to evaluate the HD surface contamination in multiple pharmacy and nursing areas that include standardized cleaning techniques and utilization of closed system transfer devices. Methods This study was conducted at six different areas in the pharmacy and nursing areas. Each area was assessed three times for five different HD’s surface contamination at an initial, 3 month, and 6 month follow up. Hazardous drug surface testing was performed for five most compounded HDs. A total of 90 individual samples were taken and analyzed during the study. Results A total of 30 samples were collected at three different timepoints for a total of 90 individual samples and analysis results. All 90 samples were negative (below the lower limit of detection; 0.01 ng/cm 2 ), for their respective drug residue. Conclusions The method and design described in this evaluation may offer a way to determine if a facility’s current HD work practices and controls retain reduced HD surface contamination based upon published threshold values. Adoption and utilization of standardized work, including use of a closed system transfer device, and cleaning practices, described in this study, may present an option for facilities to retain reduced HD surface contamination, based upon previously determined threshold values.

Objectives Amiodarone hydrochloride is a class III antiarrhythmic drug indicated for the treatment of ventricular and supraventricular tachycardias. Oral amiodarone is only available in a tablet dosage form, which is not suitable for pediatric use. The stability of amiodarone hydrochloride suspension at 5 mg/mL was assessed in SyrSpend ® SF PH4 (liquid) but oral amiodarone is typically given as a loading dose of 10–15 mg/kg/day for 4–10 days and then reduced to a maintenance dose of 5 mg/kg/day, making the 20 mg/mL concentration a better option. A hospital preparation of 20 mg/mL amiodarone hydrochloride oral suspension was developed. The purpose of this study was to determine the physicochemical stability of a 20 mg/mL amiodarone hydrochloride oral multidose suspension in a commercial compounding excipient, SyrSpend ® SF PH4 (liquid) at ambient temperature and under dark conditions. Methods Three batches of oral suspension were prepared using amiodarone hydrochloride powder and SyrSpend SF PH4 (liquid). The suspensions were stored at room temperature and protected from light (amber glass vials). A sample was withdrawn from each bottle immediately after preparation and at 1, 2, 5, 10, 15, 30, 60, and 90 days. After additional dilution to an expected concentration of 100 μg/mL with methanol, the samples were assayed in triplicate using a stability-indicating high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. The physicochemical properties (pH, osmolality, amiodarone concentration, macroscopic changes) were assessed over 90 days at each day of analysis. Stability was determined by evaluating the percentage of the initial concentration remaining at each time point and defined as retention of at least 95% of the initial concentration of amiodarone hydrochloride. Results After 90 days, the study showed that amiodarone hydrochloride concentrations did not go below 95% of the initial drug concentration. Neither degradation products nor changes of physicochemical properties were detected. Conclusions Compounded oral suspensions of 20 mg/mL amiodarone hydrochloride in SyrSpend ® SF PH4 (liquid) were stable for at least 90 days when stored in amber glass bottles at room temperature.

Objectives Azacitidine is a pyrimidine nucleoside analogue whose stability is temperature dependent. Numerous publications have studied the stability of this drug with discordant results. The purpose of this work is to study the stability of azacitidine suspensions under different conditions to allow preparation in advance: vials stored at room temperature or between 2 and 8 °C, reconstituted with refrigerated water for injection (WFI) or frozen/thawed WFI, azacitidine suspensions stored at room temperature, 2–8 °C or at −20 °C. The feasibility of a vented ChemoClave ® Spike vial was also tested to reconstitute and collect azacitidine to aid the preparation stage. Methods The stability study was performed by HPLC coupled to a photodiode array detector. The method was validated according to ICH Q2(R1). Two syringes were prepared for each analysis condition and two samples were realised for each syringe at each time of the analysis. For a storage at 2–8 °C, analyses were performed for up to 168 h. The stability was studied after 2 h at room temperature. For frozen storage, the stability was studied after 28 days. Results Azacitidine 25 mg/mL suspensions stored between 2 and 8 °C, prepared with refrigerated WFI or frozen/thawed WFI, retained more than 90% of the initial concentration for 96 h and then for 2 h at room temperature. Prepared with frozen/thawed WFI, azacitidine 25 mg/mL suspensions stored at −20 °C for 28 days and then 72 h between 2 and 8 °C after thawing, retained more than 90% of the initial concentration. When using a Spike system compared to using a needle for reconstitution and collection of the suspension, the results obtained by HPLC showed a decrease of 1.47% in the concentration of azacitidine. The comparisons of the volumes withdrawn after reconstitution were similar when using a Spike system or a needle. Conclusions Azacitidine 25 mg/mL suspensions reconstituted with refrigerated WFI were chemically stable for 4 days when stored at 2–8 °C whatever the storage of vials (refrigerator or room temperature), and 2 h at room temperature. A storage of azacitidine 25 mg/mL suspensions in syringes prepared with frozen/thawed WFI at −20 °C has been validated for up to 28 days, leading to the possibility to prepare in advance. A Spike device can be used to reconstitute and collect azacitidine.

Objectives Patients hospitalized in intensive care units often require multiple drug infusions. Due to limited intravenous accesses, concomitant administration of drugs in the same infusion line is often necessary. Compatibility studies of Y-site administration are available in the literature, but data of several combinations are lacking. Previous work from d’Huart et al. have performed an observation of the administration of injectable drugs in three adults ICUs and identified a list of Y-site administration without compatibility data. The objective of this study was to test the physical compatibility of the main drugs of this list used in pairs in Y-site infusions in critical care units, in order to provide new compatibility data to the literature, and to secure the administration of intravenous drugs. Methods The physical compatibility in Y-site of nine drugs with other drugs commonly used in intensive care units has been tested. Examinations were performed on 75 mixtures after their preparation, after 1 and 4-h storage. This evaluation included a visual examination with a search for precipitation formation, color change, gas formation, and a subvisual evaluation: absorbance measurements by UV-visible spectrophotometry at 350, 410 and 550 nm, and Light Obscuration Particle Count Test. The pH evaluation was performed at each time of analysis. Results Laboratory tests led to an overall compatibility of 68.0% for all mixtures obtained in this study. Nefopam was found to be quite compatible with other drugs (95.0%). Amiodarone hydrochloride (84.6%), acetylsalicylic acid (80.0%), clonidine hydrochloride (75.0%) and insulin (71.4%) were compatible with other drugs too. Atenolol (42.9%), furosemide (25.0%), heparin sodium (25.0%) showed less compatible results. Pantoprazole sodium (0.0%) was not at all compatible with the other drugs analyzed. Conclusions By the results of these laboratory tests, missing compatibility data are now available, providing additional information to the literature.

Objectives In adult intensive care patients, epinephrine is mostly administered by continuous injection with syringe pumps. The objective of this study was to investigate the physicochemical stability of pharmacy prepared ready-to-use epinephrine (E) 0.02 mg/mL injection solutions (total volume 50 mL) for assigning shelf-life. Methods E 0.02 mg/mL injection solution in 50 mL amber type l glass vials was produced batch-wise in the pharmacy department. Stability of the refrigerated (2–8 °C) product was investigated in real time over a period of 36 months by analyzing E concentrations, osmolality, pH, and sub-visible particles at predefined time-points. For E concentration measurements a stability-indicating, validated reversed-phase HPLC-PDA assay was used. Results The autoclaving process of E 0.02 mg/mL injection solution in 50 mL amber type I glass vials caused 5% loss of the active substance. The finished product remained stable over the study period of 36 months when stored refrigerated. Conclusions Batch-wise production of ready-to-use E injection solution 0.02 mg/mL in 50 mL amber glass vials was successfully implemented in our pharmacy department. According to the stability tests, a shelf-life of 36 months can be assigned to the finished product stored refrigerated. Studies concerning stability at room temperature would be useful.

Objectives The objective of this study was to investigate the physicochemical stability of ready-to-adminster human insulin (HI) 1 I.U./mL injection solutions of two different brand products diluted with 0.9% NaCl solution under different storage conditions either in 50 mL disposable plastic syringes or as bulk solution in infusion bags. Methods HI test solutions 1 I.U./mL were prepared with Huminsulin ® Normal 100 and Actrapid ® Penfill ® , diluted with 0.9% sodium chloride infusion solution, and filled in Original-Perfusor ® syringes or BD ® Perfusion syringes. Test solutions were stored for 90 days at 2–8 °C/dark or at 20–25 °C/diffuse room light. Bulk solutions 1 I.U./mL prepared with Huminsulin ® Normal 100 were stored in two different 3 L infusion bags (Ecobag ® click and ExactaMix ® EVA bag) at 2–8 °C/dark for five days. HI concentrations were determined by reversed-phase high-performance liquid chromatography at predefined time points. Beside regular visual inspection, subvisible particles and pH values were measured. Results Ready-to-adminster Huminsulin ® Normal and Actrapid ® Penfill ® injection solutions 1 I.U./mL prepared in 50 mL Original-Perfusor ® syringes or BD ® Perfusion syringes remained physicochemically stable for up to 90 days when stored at 2–8 °C/dark and for at least 14 days when kept at 20–25 °C/diffuse room light. Prefilled 3 L polyolefin infusion bags (Ecobag ® click) are suitable for the preparation of Huminsulin ® 1 I.U./mL bulk solutions. In ethylene vinyl acetate (EVA) bags, HI concentrations decreased rapidly. Conclusions Ready-to-administer Huminsulin ® Normal and Actrapid ® Penfill ® injection solutions 1 I.U./mL can be prepared in advance by dilution with 0.9% sodium chloride infusion solution and filled into 50 mL Original-Perfusor ® syringes or BD ® Perfusion syringes; subsequent storage at 2–8 °C/dark is possible for up to 90 days. For preparation of bulk solutions, the prefilled polyolefin infusion bag is appropriate.