Corredor Claudia C, Haby Thomas A, Young Joel D, Shah Pankaj A, Varia Sailesh A
Analytical Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 191, New Brunswick, NJ 08903, USA.
PDA J Pharm Sci Technol. 2009 Nov-Dec;63(6):527-36.
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.
使用三种不同的溶媒（含20% w/v磺丁基醚-β-环糊精的pH 3柠檬酸盐缓冲液、pH 8磷酸盐缓冲液以及50/50 v/v聚氧乙烯蓖麻油/无水乙醇），对五种常用的瓶塞配方进行了可提取物测试。这些瓶塞由丁基橡胶和卤化丁基橡胶制成，有涂层和无涂层的专有薄膜，在40℃/75%相对湿度（RH）下与每种溶媒接触储存长达6个月，或在25℃/60% RH下储存长达24个月。使用电感耦合等离子体原子发射光谱法、离子色谱法、高效液相色谱法和气相色谱法分析样品中可提取物的存在情况。在测试的五个瓶塞中，只有一个的可提取物含量超过了10 ppm。基于这些结果，制定了瓶塞可提取物测试的标准化方案。该方案已用于满足多种不同新型注射产品的瓶塞可提取物测试监管要求。
