The Effect of Temperature, pH, and Different Solubilizing Agents on Stability of Taxol

Inabilities to attain adequate aqueous solubility and stability have made the preparation of a clinically suitable formulation of taxol difficult. Addition of nicotinamide (ND), 2-hydroxypropyl--cyclodextrin (HPßCD), polyethylene glycol, (PEG), bile salts (BS, 50:50 sodium cholate: deoxycholate), and cremophor EL can improve the solubility of taxol. Studies were undertaken to compare the stability of taxol in HPßCD (20%), ND (20%), PEG (20%), BS (20%), and cremophor EL (cremophor: ethanol 0.5% of each) solutions at 25, 37, 50, and 60 oC. Taxol concentration was measured by HPLC method. The rate of degradation proceeded in a Log-linear fashion and increased progressively with the elevation of temperature in all solutions except in HPCD which taxol had negligible degradation. In the absence of added agents, taxol exhibited the lowest and highest stability at pH 1.2 and 4.5, respectively. Taxol was most stable in HPCD followed by PEG and then ND. The stability of taxol increased linearly with the HPCD concentration (0-5% w/v). Due to the observed improved stability and solubility, HPCD may be considered for pharmaceutical studies as a suitable stabilizer for formulation of taxol.