Preparation of and drug release from W/O/W type double emulsions containing anticancer agents.

Abstract

Water-in-oil-in-water (W/O/W) type double emulsions were prepared by 2-step emulsification procedures. The structures of W/O/W type double emulsions and the release characteristics of cytarabine and 5-fluorouracil (5-FU) from W/O/W type double emulsions were studied. W/O/W type double emulsions were ruptured within 24 h when sorbitan monooleate (SO-10) or sorbitan sesquioleate (SO-15) was used as a lipophilic emulsifier. W/O/W type double emulsions prepared in a hydrogenated castor oil (HCO-10) in peanut oil were still intact after 24 h. Therefore, the release characteristics of drugs were studied in HCO-10 in peanut oil. The release of cytarabine from W/O/W type double emulsions was very prolonged. The release of cytarabine was enhanced with an increase in the volume of inner aqueous phase or an increase in the concentration of HCO-10. The concentration of cytarabine and the concentration of a hydrophilic emulsifier (HCO-60) had little effect on the release of cytarabine. Whereas the release of 5-FU from W/O/W type double emulsions was as fast as from a simple solution, the release was very prolonged when the pH of the inner aqueous phase was adjusted to 10.0. Thus, W/O/W type double emulsions are useful for sustained release preparations, and the control of drug release from W/O/W type double emulsions may be possible.