STABILITY, COMPATIBILITY AND PLASTICIZER EXTRACTION OF MICONAZOLE INJECTION ADDED TO INFUSION SOLUTIONS AND STORED IN PVC CONTAINERS

The stability of miconazole in various diluents and polyvinyl chloride (PVC) containers was determined and the release of diethylhexyl phtha late (DEHP) from PVC bags into intravenous infusions of miconazole was measured. An injection formulation (80 mi) containing a 1% solution o f miconazole with 11.5% of Cremophor EL was added to 250-ml PVC infusi on bags containing 5% glucose injection or 0.9% sodium chloride inject ion, to give an initial nominal miconazole concentration of 2.42 mg ml (-1), the mean concentration commonly used in clinical practice. Sampl es were assayed by stability-indicating high-performance liquid chroma tography (HPLC) and the clarity was determined visually. Experiments w ere conducted to determine whether the stability and compatibility of miconazole would be compromised, and whether DEHP would be leached fro m PVC bags and PVC administration sets during storage and simulated in fusion. There was no substantial loss of miconazole over 2 h simulated infusion irrespective of the diluent, and over 24 h storage irrespect ive of temperature (2-6 degrees C and 22-26 degrees C). All the soluti ons initially appeared slightly hazy. Leaching of DEHP was also detect ed during simulated delivery using PVC bags and PVC administration set s. There was a substantial difference between the amounts of DEHP rele ased from PVC bags and from administration sets, and also between the amounts released in solutions stored in PVC bags at 2-6 degrees C and 22-26 degrees C over 24 h. At the dilution studied, miconazole was vis ually and chemically stable for up to 24 h. The storage of miconazole solutions in PVC bags seems to be limited by the leaching of DEHP rath er than by degradation. To minimize patient exposure to DEHP, miconazo le solutions should be infused immediately after their preparation in PVC bags.