Physicochemical stability study of cabazitaxel Zentiva^® in vials after “opening” and in diluted solutions in 3 types infusion bags

Introduction
To our knowledge, few studies have been published on the stability of cabazitaxel in infusion bags. The 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.

Objectives
The aim of this work was to study the physicochemical stability of cabazitaxel Zentiva^® solutions in vials after “opening” with a Spike at 25°C, and in solutions diluted at 0.1 and 0.26 mg/mL in 0.9% NaCl or D5W (dextrose 5% in water) in 3 types of infusion bags (Easyflex^® and Viaflo^® at 25°C, Freeflex® between 2-8°C) for 28 days.

Materials and 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 ICHQ2(R1) standards. For the study in infusion bags, three preparations were made for each condition. At each analysis time, a sample for each infusion bag was prepared and analyzed by HPLC. Two vials after “openings” were stored at 25°C and three samples per vial were prepared and analyzed at the 3 analysis times. Physical stability was assessed by visual examination (change in colour, appearance of precipitate, gaz). The pH of the solutions in the bag 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^® bags (polyolefin), Viaflo^® bags (multilayer high density polyethylene (HDPE), polyamide, polypropylene) retained more than 95% of the concentration for 28 days at 25°C. In Freeflex^® bags (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 2-8 °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 the solutions in the bags were constant over time over the period analyzed. Additional peaks are present in very small proportions and vary little over time.

Conclusion
Cabazitaxel Zentiva^® solutions diluted at 0.1 and 0.26 mg/mL in 0.9% NaCl or D5W are stable for 28 days at 25°C and between 2-8°C. This stability data allows preparations to be made in advance. The cabazitaxel vial with a Spike is stable for 28 days at 25°C, allowing the remainder of the vial to be used over several days.

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