|
Etoposide, a semisynthetic epipodophyllotoxin derivative, is a cytotoxic drug widely used in cancer chemotherapy. Etoposide has low aqueous solubility and is administered by slow intravenous infusion in the concentration of 0.2 to 0.4㎎/㎖. The effects of modified β-cyclodextrins (β-CDs) on the water solubility of etoposide and in vitro precipitation of etoposide upon dilution with human plasma were studied, and their effects on the physical and chemical stability of etoposide were observed. Chemical stability was measured by a stability-indicating reversed-phase high-performance liquid chromatographic assay. Physical stability was checked by visual and microscopic inspection. The aqueous solubility of etoposide in the presence of CDs was increased in the rank order of β-CD < 2-hydroxypropyl-β-cyclodextrin (HPCD) < sulfobutyl ether β-cyclodextrin (SBCD). In the presence of 2％ SBCD or HPCD, etoposide(0.4㎎/㎖) in 5％ dextrose injection was not precipitated, and chemically stable for 72 hr at 4℃. With the addition of 5％ SBCD, etoposide(0.5 and 0.6㎎/㎖) in 5％ dextrose and normal saline infusion fluids was physically and chemically stable over 48 hr at room temperature. Dilutions(1：1 to 1：20) of etoposide(0.6㎎/㎖) in normal saline containing 5％ SDCD with human plasma resulted in no precipitation for 24 hr. In conclusion, SBCD was effective in the prevention of precipitation of etoposide in the infusion fluid.
|