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 To the best of our knowledge, few studies have been published on the stability of cabazitaxel in infusion bags. Stabilis® database has selected a study demonstrating the stability of this molecule at 0.15 mg/mL for 28 days at 4 °C and 25 °C in polyolefin bags. The aim of this work was to study the physicochemical stability of Cabazitaxel Zentiva® solutions in vials after “opening” with a vented ChemoClave® Spike, at 25 °C, protected from light and in solutions diluted at 0.1 and 0.26 mg/mL in 0.9 % sodium chloride (0.9 % NaCl) or dextrose 5 % (D5W) in 3 types of infusion bags (Easyflex® and Viaflo® at 25 °C, Freeflex® between 2 and 8 °C, protected from light). Methods The chemical stability was analyzed after preparation and then after 14 and 28 days of storage by high performance liquid chromatography (HPLC), coupled to a diode array detector, at the analysis wavelength of 232 nm. The method has been validated according to ICH Q2 (R1) standards. For the study in infusion bags, three preparations were realised for each condition. At each time of analysis, for each bag, a sample was prepared and analyzed by HPLC. Two vials after “openings” were kept at 25 °C and three samples per vial were prepared and analyzed at the three analysis times (D0, D14 and D28). Physical stability was assessed by visual examination (change in colour, appearance of precipitate, gas formation). The pH of the solutions prepared in infusion bags was evaluated at each analysis time. Results Cabazitaxel solutions at 0.1 and 0.26 mg/mL diluted in 0.9 % NaCl or D5W in Easyflex® (polyolefin), Viaflo® (multilayer high density polyethylene, polyamide, polypropylene) bags retained more than 95 % of the concentration after 28 days at 25 °C. In the Freeflex® bag (polypropylene multilayers), cabazitaxel solutions at 0.1 and 0.26 mg/mL diluted in 0.9 % NaCl or D5W retained more than 95 % of the initial concentration between 2 and 8 °C for 28 days. In vials with a Spike, cabazitaxel solutions at 20 mg/mL retained more than 95 % of the initial concentration for 28 days at 25 °C. For all the conditions studied, no visual modification was observed. The pH of solutions in bags were constant during the stability study. Conclusions Cabazitaxel Zentiva® diluted at 0.1 and 0.26 mg/mL in 0.9 % NaCl or D5W was stable for 28 days at 25 °C and between 2 and 8 °C. These stability data allow preparations to be made in advance. The remainder of the cabazitaxel vial fitted with a Spike was stable for 28 days at 25 °C, allowing the remainder of the vial to be used over several days.
Objectives The measurement of osmolality is used by many authors as an additional stability criterion of a drug in solution. In the current state of knowledge, no scientific publication correlates the osmolality values and the stability of a solution. To study the relevance of this analytical technique by measuring the osmolality of injectable solutions whose instability has been chemically demonstrated by high performance liquid chromatography (HPLC). Methods Selection of 13 drug preparations whose chemical instability has been demonstrated in the literature. Realization of three identical samples per selected preparation and measurements of the osmolality of the freshly prepared solutions, then, at various storage times until a chemical degradation of the molecule validated by HPLC of at least 10% and possibly up to 40%. Results Measurements of the osmolality were performed on five antibiotics (amoxicillin/clavulanic acid, cefepime, cefoxitine, meropenem and temocillin and cefoxitin) and five anticancer drugs (azacitidine, bendamustine, busulfan, fotemustine and oxaliplatin). Osmolality varied from −6.30 to 11.10% for antibiotics and from 0.57 to 2.04%. Conclusions Among the preparations tested, only two formulations have a variation in osmolality in accordance with the chemical degradation. For the other 11 formulas, the variations in osmolality values where not correlated with the degradation measured by HPLC. In view of these results, osmolality does not seem to be a criterion of choice for the study of drug stability. In the majority of the unstable solutions studied, the variation of osmolality measurements does not correlate with the loss of concentration and the appearance of degradation products.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.