Stability, compatibility and plasticizer extraction of miconazole injection added to infusion solutions and stored in...

The stability of miconazole in various diluents and polyvinyl chloride (PVC) containers was determined and the release of diethylhexyl phthalate (DEHP) from PVC bags into intravenous infusions of miconazole was measured. An injection formulation (80 ml) containing a 1% solution of miconazole with 11.5% of Cremophor EL was added to 250-ml PVC infusion bags containing 5% glucose injection or 0.9% sodium chloride injection, to give an initial nominal miconazole concentration of 2.42 mg ml-1, the mean concentration commonly used in clinical practice. Samples were assayed by stability-indicating high-performance liquid chromatography (HPLC) and the clarity was determined visually. Experiments were conducted to determine whether the stability and compatibility of miconazole would be compromised, and whether DEHP would be leached from PVC bags and PVC administration sets during storage and simulated infusion. There was no substantial loss of miconazole over 2 h simulated infusion irrespective of the diluent, and over 24 h storage irrespective of temperature (2-6 degrees C and 22-26 degrees C). All the solutions initially appeared slightly hazy. Leaching of DEHP was also detected during simulated delivery using PVC bags and PVC administration sets. There was a substantial difference between the amounts of DEHP released 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 visually 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 rather than by degradation. To minimize patient exposure to DEHP, miconazole solutions should be infused immediately after their preparation in PVC bags.