Solubility and stability of taxol: Effects of buffers and cyclodextrins

The degradation kinetics of taxol in aqueous solutions were investigated at 37 degrees C over a pH range of 1-9. The hydrolysis rates followed pseudo first-order kinetics with respect to residual taxol concentration. The pH-rate profile at 37 degrees C showed that a maximum stability of taxol occurred in the pH 3-5 region. The effect of gamma-cyclodextrin (gamma CD), hydroxypropyl-gamma-cyclodextrin (HP gamma CD) and hydroxypropyl-beta-cyclodextrin (HP beta CD) on the solubility and stability of taxol was also investigated. Taxol was more stable in cyclodextrin solution than in buffer solution of comparable pH. The solubility of taxol in water increased in the presence of cyclodextrins with HP beta CD giving the greatest increase in taxol solubility. Taxol (as received) was anhydrous and on suspension in water, it dissolved to form a supersaturated solution which recrystallized as a hydrate of lower solubility. Taxol formed predominantly second order complexes with the cyclodextrins. Complexes of taxol with HP beta CD were more stable than those of HP gamma CD or gamma CD. Further increase in the solubility of taxol was observed when ethanol was added as a co-solvent.