title: Comprehensive determination of extractables from five different brands of stoppers used for injectable products.
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.
authors.affiliation: Analytical Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 191, New Brunswick, NJ 08903, USA. claudia.corredor@bms.com
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Corredor
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Haby
authors.forename: Joel D
authors.initials: JD
authors.lastname: Young
authors.forename: Pankaj A
authors.initials: PA
authors.lastname: Shah
authors.forename: Sailesh A
authors.initials: SA
authors.lastname: Varia
mesh_terms: D002845:Chromatography / Q000379:methods; D004349:Drug Packaging / Q000592:standards*; D004355:Drug Stability; D004356:Drug Storage; D020724:Elastomers / Q000737:chemistry*; D006813:Humidity; D006863:Hydrogen-Ion Concentration; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D013054:Spectrophotometry, Atomic; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013997:Time Factors
chemical_list: D020724:Elastomers; D014677:Pharmaceutical Vehicles; C017098:butyl rubber