Particulate contamination from siliconized rubber closures for freeze drying.
It can be shown that siliconized closures for freeze drying may cause the opalescence and turbidity observed in freeze-dried products after reconstitution. Closures of different rubber composition show different intensities of turbidity when treated identically with the same quantity and type of silicone oil. Clear solutions are obtained after reconstitution if ETFE-coated closures are used instead of siliconized closures. Samples stored at 4 degrees C for up to 6 months show no change in the intensity of turbidity, while the turbidity of samples manufactured with siliconized closures and stored at higher temperatures increase with time. Samples with ETFE-coated closures show clear solutions when stored at 25 degrees C and 37 degrees C for up to 6 months and at 45 degrees C for 3 months. After 6 months only a very weak opalescence could be observed in these samples.
Gebhardt
U
U
Parke-Davis Pharmaceutical Research, Freiburg, Germany.
Grumbridge
N A
NA
Knoch
A
A
D004340:Drug Contamination; D004349:Drug Packaging; D005612:Freeze Drying; D009391:Nephelometry and Turbidimetry; D012826:Silicone Elastomers / Q000737:chemistry*
D012826:Silicone Elastomers