Compatibility and stability of paclitaxel combined with doxorubicin hydrochloride in infusion solutions.

Abstract

To evaluate the physical compatibility and chemical stability of paclitaxel at concentrations of 300 and 1200 micrograms/mL with doxorubicin hydrochloride 200 micrograms/mL in NaCl 0.9% injection and dextrose 5% injection over 7 days at 4, 23, and 32 degrees C. The test samples were prepared in polyolefin bags of the infusion solutions at the required drug concentrations. Evaluations were performed initially and after 4 hours, and 1, 3, 5, and 7 days of storage at 4, 23, and 32 degrees C for physical and chemical stability. Physical stability was assessed by using visual observation in normal fluorescent light and a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the two drugs was evaluated by using two stability-indicating HPLC analytic techniques. All samples were physically stable through 1 day. However, microcrystalline precipitation of paclitaxel occurred within 3 days in some samples and within 5 days in all samples. Paclitaxel concentrations remained at more than 97% in all samples throughout the study. Doxorubicin hydrochloride also was stable throughout the study period, remaining above 90% in all samples at all storage temperatures. Admixtures of paclitaxel 300 and 1200 micrograms/mL with doxorubicin hydrochloride are limited in their utility time by paclitaxel microcrystalline precipitation. All combinations were physically and chemically stable for at least 24 hours at 4, 23, and 32 degrees C.