ABSTRACT
Five commonly used stopper formulations were tested for extractables using three different vehicles (pH 3 citrate buffer with 20% w/v sulfobutylether-beta-cyclodextrin, pH 8 phosphate buffer and 50/50 v/v polyoxyethylated castor oil/dehydrated alcohol). The stoppers, made from butyl and halobutyl rubbers, coated and uncoated with proprietary films, were stored in contact with each vehicle for up to 6 months at 40 degrees C/75% relative humidity (RH) or for up to 24 months at 25 degrees C/60% RH. Samples were analyzed for the presence of extractables using inductively coupled plasma-atomic emission spectroscopy, ion chromatography, high-performance liquid chromatography, and gas chromatography. Extractables were observed at greater than 10 ppm for only one of the five stoppers that were tested. Based on these results, a standardized protocol for stopper extractable testing was developed. This protocol has been used to satisfy stopper extractable testing regulatory requirements for a number of different new injectable products.
