Removal of Residual Toluene and Methyl Tertiary Butyl Ether from Amorphous Paclitaxel by Simple Rotary Evaporation with Alcohol Pretreatment

In this study, a drying method was developed for effective removal of residual solvents from toluene- or methyl tertiary butyl ether-induced amorphous paclitaxel. By simple rotary evaporation with alcohol pretreatment, there was sufficient removal of the residual toluene, methyl tertiary butyl ether, methanol, and ethanol concentrations of paclitaxel to bring them below the ICH-specified values (890, 5000, 3,000, and 5,000 ppm). In addition, SEM analysis and ultrasonic treatment revealed that residual solvent removal was associated with the formation of pores on the surface of the sample because of the high vapor pressure of the toluene-alcohol mixture or the methyl tertiary butyl ether-alcohol mixture and hydrogen bonding between the solvent and the alcohol.