Stability of paclitaxel with ondansetron hydrochloride or ranitidine hydrochloride during simulated Y-site administration.

The stability of paclitaxel with either ondansetron hydrochloride or ranitidine hydrochloride during simulated Y-site injection at room temperature was studied. Triplicate test solutions of paclitaxel 0.3 and 1.2 mg/mL were admixed 1:1 with ondansetron 0.03 and 0.3 mg/mL (as the hydrochloride salt) or ranitidine 0.5 and 2.0 mg/mL (as the hydrochloride salt). Also, paclitaxel 1.2 mg/mL was admixed 1:1:1 with ondansetron 0.3 mg/mL and ranitidine 2.0 mg/mL. The solutions were stored in glass containers at room temperature, and samples were removed at zero, one, two, and four hours for immediate assay. At the time of the assay and before any dilution, each sample was visually inspected for clarity, color, and precipitation, and the pH was determined. Drug concentrations were measured by stability-indicating high-performance liquid chromatographic procedures. Throughout the study, more than 90% of the initial concentrations of paclitaxel, ondansetron, and ranitidine remained in the solutions. No precipitates, color changes, or haziness was seen. The changes in pH were minor. Paclitaxel in concentrations of 0.3 and 1.2 mg/mL was stable when mixed with either ondansetron (0.03 or 0.3 mg/mL, as the hydrochloride salt) or ranitidine (0.5 or 2.0 mg/mL, as the hydrochloride salt) and stored in glass containers for four hours. Paclitaxel 1.2 mg/mL was also stable when mixed with both ondansetron 0.3 mg/mL and ranitidine 2.0 mg/mL and stored in glass containers for four hours.

Paclitaxel stability and compatibility in polyolefin containers.

OBJECTIVE: To determine the compatibility and stability of paclitaxel in polyolefin containers. DESIGN: The following paclitaxel concentrations were determined by a stability-indicating HPLC method: 0.3 and 1.2 mg/mL diluted in dextrose 5% for injection, USP (D5W) or sodium chloride 0.9% for injection, USP (NS). The solutions were prepared in polyolefin containers and the stability and compatibility were monitored for 48 hours when stored at ambient temperature (20-23 degrees C) and normal fluorescent lighting. A mixture of the drug carrier consisting of approximately 10% polyoxyethylated castor oil (Cremophor EL) and 10% ethanol in D5W and NS, without paclitaxel, was studied to differentiate the effect of paclitaxel from the effect of the drug carrier on the container. Paclitaxel concentrations, pH changes, and visual clarity were used as stability and compatibility indicators. RESULTS: Paclitaxel concentrations remained at 96-99 percent of the initial concentration for up to 48 hours when placed in the polyolefin containers. No changes in color or visual clarity were noted. Only minor changes in the pH of the admixtures were observed. CONCLUSIONS: Paclitaxel diluted in D5W or NS at concentrations of 0.3 and 1.2 mg/mL is stable and compatible in flexible, polyolefin containers for up to 48 hours.