Self-emulsifying O/W formulations of paclitaxel prepared from mixed nonionic surfactants

Nonionic self-emulsifying oil-in-water (O/W) formulations free of Cremophore® were developed as drug delivery vehicles for paclitaxel. The surfactants used included phosphatidylcholine purified from egg yolk (EPC), Tween, and Span. Oils phases were either pure components or blends from benzyl alcohol, 2-phenylethanol benzyl benzoate, and tributyrin. Among these surfactants, mixtures of EPC and Tween-80 gave really stable emulsions in proper sizes ranging from 70 to 200 nm, mainly depends on the ratio of EPC to Tween-80 and amount of oils. Paclitaxel could be well preserved without any loss in oily stocks, namely mixtures of oils and paclitaxel as well as surfactants, stored at 4°C for more than 8 months. Only gentle mixing on oily stocks with aqueous diluents is enough to make paclitaxel-contained emulsions. The optimum formulation contains oils from 1 to 3 wt%, Tween-80 and EPC from 0.4 to 1.2 wt%, respectively. Consequently, near 500 ppm of paclitaxel can be contained in emulsions. Moreover, these paclitaxel-containing emulsions are compatible with commonly used injection fluids. No precipitation is observed upon preparation of emulsion from dilution of oily stocks. Negligible cytotoxicity on these emulsions assessed with NIH/3T3 cells implied their good biocompatibility and promising applications as drug delivery carriers. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2320-2332, 2010