earticle

영어

The solvent evaporation process is a convenient method for controlling the morphologies of paclitaxel. Amorphous paclitaxel was simply made by dissolving paclitaxel in methylene chloride/methanol (98/2, v/v) and in relatively non-polar solvents (t-butyl methyl ether, pentane, acetonitrile/hexane (1/2, v/v), methylene chloride, chloroform, toluene). On the other hand, crystalline paclitaxel was made by dissolving paclitaxel in a special polar solvent containing a small amount of water. However, when we used only methanol, we got mixed morphologies of paclitaxel made of both the crystalline and amorphous forms. Their physicochemical properties were investigated by X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and high performance liquid chromatography (HPLC). The initial water content of amorphous paclitaxel and crystalline paclitaxel was determined for 0.65 wt% and 5.85 wt%, respectively. The hygroscopic property of crystalline paclitaxel was very changeable in all given humidity (15, 60, 95 RH%) during storage. Dissolution profiles for paclitaxel showed that amorphous paclitaxel measured the highest solubility in water and its solubility held most stable during the measurements. The residual solvent could be reduced to the maximum allowed value (600 ppm for methylene chloride, 3,000 ppm for methanol) of guidance for the International Conference on Harmonization (ICH) by spray drying.