Design and evaluation of an emulsion vehicle for paclitaxel. II. Suppression of the crystallization of paclitaxel by freeze-drying technique

Although paclitaxel is soluble in vitamin E up to 40 mg per g, crystallization was detected at loadings higher than 15 mg per g. Water appeared to be an important factor causing the observed crystallization, and therefore, a freeze-drying technique was investigated to produce reconstitutible vitamin E emulsions, to increase drug loading without crystal formation after reconstitution. The emulsion was freeze-dried using a laboratory freeze-drier and the droplet size was measured using dynamic light scattering. The freeze-dried emulsions using sucrose as a cryoprotectant could be easily reconstituted. The loading of paclitaxel in the freeze-dried emulsions could be increased to 25 mg per g of vitamin E without crystal formation, and the mean emulsion droplet size remained smaller than 0.2 mu m over 430 days (4 +/- 2 degrees C). The previously observed surfactant-enhanced crystallization could also be suppressed using the freeze-drying technique.