Physicochemical stability of Cabazitaxel Zentiva® solution in vials after opening and diluted solutions in three infusion bags

Abstract

Abstract 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.