Physical and chemical stability of paclitaxel infusions in different container types

Abstract

To determine the physicochemical stability of generic (Teva Pharmaceuticals) paclitaxel infusions (0.3 and 1.2 mg/mL) in 0.9% sodium chloride or 5% glucose in polyolefin (Viaflo), low-density polyethylene (Ecoflac), and glass containers at 2-8 and 25 degrees C. Paclitaxel infusions of various concentration/diluent/container combinations were prepared. Containers were light-protected and incubated at test temperatures with further analysis at predetermined intervals of 1-3 days for up to 30 days. Infusions were monitored for pH, weight loss, precipitation, colour change, and subvisual particulates as indicators of physical stability, and assayed for drug concentration to determine chemical stability. Precipitation was the limiting factor. Infusions of paclitaxel (0.3 mg/mL) in 0.9% sodium chloride remained stable for 13, 16 and 13 days at 2-8 degrees C in polyolefin, low-density polyethylene and glass containers, respectively; in 5% glucose for 13, 18, and 20 days, respectively. At 25 degrees C, paclitaxel infusions (0.3 mg/mL) remained stable for 3 days in all diluent/container combinations with the exception of 5% glucose in glass, where stability reached 7 days. Paclitaxel infusions (1.2 mg/mL) in 0.9% sodium chloride remained stable for 9, 12, and 8 days at 2-8 degrees C in polyolefin, low-density polyethylene and glass containers, respectively; in 5% glucose for 10, 12, and 10 days, respectively. At 25 degrees C, paclitaxel 1.2 mg/mL remained stable for 3 days in all diluent/container combinations with the exception of glass, where stability reached 5 days in 0.9% sodium chloride diluent, and 7 days in 5% glucose. Paclitaxel stability was influenced by storage temperature, with longer shelf-life at 2-8 degrees C, and also by drug concentration, where 0.3 mg/mL infusions were more stable than 1.2 mg/mL for all diluent/container combinations. Physical stability (precipitation) was the limiting parameter in each case.