Leaching of Diethylhexyl Phthalate from Polyvinyl Chloride Containers by Selected Drugs and Formulation Components

Abstract

The extent of leaching of diethylhexyl phthalate (DEHP) from polyvinyl chloride (PVC) bags by several organic solvents and surfactants used as formulation components and by 12 drug products containing these solvents and surfactants was studied. The organic solvents ethanol, polyethylene glycol, and propylene glycol, the surfactants polysorbate 80 and polyoxyethylated castor oil, and the 12 drugs were admixed separately in PVC bags of 5% dextrose injection. At the time of preparation and after 4, 8, and 24 hours at 24 degrees C, the concentration of DEHP in duplicate samples was determined in duplicate by high-performance liquid chromatography. Ethanol, polyethylene glycol, and propylene glycol at concentrations of 25% and the drugs containing these components did not leach DEHP within the study period. Polysorbate 80 1% to 25% leached detectable amounts of DEHP in as little as one hour at the high concentration and within four hours at the lower concentrations; at 24 hours, DEHP concentrations ranged from 36 micrograms/mL for 1% polysorbate 80 to 237 micrograms/mL for 25% polysorbate 80. Similar results were observed for polysorbate 80 plus ethanol and for polyoxyethylated castor oil plus ethanol. Drug products containing surfactants, including cyclosporine, miconazole, and teniposide, and the vehicles used in formulating taxol and taxotere, leached relatively large amounts of DEHP in 24 hours. Smaller amounts were leached by chlordiazepoxide hydrochloride and etoposide. DEHP was leached from PVC containers by a variety of surfactants and drug products containing these surfactants. Drugs that leach DEHP should be prepared in non-PVC containers and administered through non-PVC tubing.