title: Effect of unpurified Cremophor EL on the solution stability of paclitaxel.
abstract: Taxol for Injection Concentrate contains a solution of paclitaxel in a 50:50 v/v mixture of Cremophor EL (cleaned):ethanol. Cleaned, rather than unpurified, Cremophor EL is used as a cosolvent because paclitaxel was observed to be less stable in the presence of unpurified Cremophor. In order to understand the cause of this paclitaxel instability, various studies were performed. The results of these studies, coupled with the examination of degradation products, suggested that carboxylate anions present in the unpurified Cremophor catalyze the degradation of paclitaxel by general base catalyzed ethanolysis. Stabilization of Taxol for Injection Concentrate prepared with unpurified Cremophor can be achieved by addition of strong acids, resulting in neutralization of the carboxylate anions. Separately, a quality control test for the cleaning procedure of Cremophor is needed to insure stability of Taxol for Injection Concentrate. A colorimetric indicator test was identified which can distinguish between good and poor quality cleaned Cremophor as it pertains to paclitaxel stability.
authors.affiliation: Bristol-Myers Squibb Co., New Brunswick, NJ 08903-0191, USA. uday.gogate@bms.com
authors.forename: Uday S
authors.initials: US
authors.lastname: Gogate
authors.forename: Philip A
authors.initials: PA
authors.lastname: Schwartz
authors.forename: Shreeram N
authors.initials: SN
authors.lastname: Agharkar
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000378:metabolism; D001978:Bromphenol Blue; D002264:Carboxylic Acids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D003124:Colorimetry; D004340:Drug Contamination; D004355:Drug Stability; D005990:Glycerol / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007267:Injections; D015394:Molecular Structure; D017239:Paclitaxel / Q000737:chemistry* / Q000378:metabolism; D010602:Pharmacopoeias as Topic; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002264:Carboxylic Acids; D007202:Indicators and Reagents; D012996:Solutions; D001978:Bromphenol Blue; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol