エトポシド注射用製剤の輸液ポンプ使用条件下における希釈後安定性の評価

抄録

Precipitation is one of the most serious incompatibilities of injections. To avoid drug precipitation in the clinical setting, pharmaceutical industries provide the physical compatibility data of their own products. However, these data were mainly obtained under a still standing condition, and therefore the effects of physical stress by infusion pump or of difference in the content of additives are largely unknown. To elucidate these problems, two different products of etoposide injection were subjected to the compatibility testing. After dilution by normal saline or 5％ glucose solution to give a final concentration of 0.2-1.0 mg/mL, diluted injections were pumped through a mid-press type peristaltic pump for 28 hours. Then, diluted injections before and after pumping (corresponding to without and with physical stress, respectively) were sampled over time. Compatibility was evaluated by the grading of insoluble particles by visual inspection, and the latest sampling time without visible insoluble particles was defined as the longest available time. In addition, the number of insoluble particles was counted using a particle counter. The longest available time was shortened by the increase of etoposide concentration, and was shorter when diluted with normal saline. In addition, the longest available time was shortened by pumping, and the magnitude of change was notably different between the two products, indicating that the additives contributed to the physical compatibility to some extent. Furthermore, the number of insoluble particles increased with the increase of the visual grading, indicating that the particle counter provides the objective criteria for the compatibility testing of injections in the clinical setting.