Zdravkovic Steven A
Pharmaceutical Product Development, Inc., Middleton, WI, USA
PDA J Pharm Sci Technol. 2017 Nov-Dec;71(6):488-501. doi: 10.5731/pdajpst.2016.007468. Epub 2017 Sep 19.
Lyophilization is commonly used to extend the shelf life of pharmaceutical products that are otherwise unstable when stored as a liquid formulation. However, the ability of a lyophilized drug, or other solid medium, to leach or extract substances from a pharmaceutical packaging material is not well characterized. To provide insight into this area of uncertainty, the extraction properties of a lyophilized drug product, the lyophilized drug product reconstituted in water, and several other solid and liquid media of varying polarity were determined using a glass vial with a butyl rubber stopper as a representative pharmaceutical packaging system. The results obtained in this study show that the extracting power of a medium, whether solid or liquid, was primarily a function of polarity. Thus, the amount of each extractable observed for the lyophilized and reconstituted drug product were in trend with the other solid and liquid media, respectively. Nevertheless, it was notable that the lyophilized drug product was able to leach substances from the stopper in quantifiable amounts, whereas the reconstituted drug product contained no detectable leachables. Using a mathematical relationship, it was determined that the extraction power of the lyophilized drug product was equivalent to a 50/50 isopropanol/water solution. Freeze drying is commonly used to extend the shelf life of pharmaceutical products that are otherwise unstable when stored as a liquid formulation. However, the propensity for substances to migrate from a pharmaceutical packaging material and into a solid drug formulation is not well characterized. To provide insight into this area of uncertainty, the migration of substances from a glass vial with a butyl rubber stopper and into a lyophilized drug product, the drug product reconstituted with water, as well as several solid and liquid media of varying polarity were assessed. The results obtained in this study show that the extracting power of a medium, whether solid or liquid, was primarily a function of polarity and thus could be related to one another. Furthermore, the results for the freeze-dried and reconstituted drug products were in trend with the other solid and liquid media tested, respectively, and showed that the freeze-dried drug was able to leach substances from the stopper in measureable amounts, whereas the reconstituted drug product contained no substances that had originated from the stopper.
冻干法通常用于延长那些以液体制剂形式储存时不稳定的药品的保质期。然而，冻干药物或其他固体介质从药品包装材料中浸出或提取物质的能力尚未得到充分表征。为了深入了解这一不确定领域，使用带有丁基橡胶塞的玻璃瓶作为代表性药品包装系统，测定了冻干药品、在水中复溶的冻干药品以及其他几种不同极性的固体和液体介质的提取特性。本研究获得的结果表明，一种介质（无论是固体还是液体）的提取能力主要是极性的函数。因此，冻干药品和复溶药品中观察到的每种可提取物的量分别与其他固体和液体介质的趋势一致。然而，值得注意的是，冻干药品能够从瓶塞中浸出可量化的物质，而复溶药品中未检测到可浸出物。通过数学关系确定，冻干药品的提取能力相当于50/50的异丙醇/水溶液。冷冻干燥通常用于延长那些以液体制剂形式储存时不稳定的药品的保质期。然而，物质从药品包装材料迁移到固体药物制剂中的倾向尚未得到充分表征。为了深入了解这一不确定领域，评估了物质从带有丁基橡胶塞的玻璃瓶迁移到冻干药品、用水复溶的药品以及其他几种不同极性的固体和液体介质中的情况。本研究获得的结果表明，一种介质（无论是固体还是液体）的提取能力主要是极性的函数，因此它们之间可以相互关联。此外，冻干药品和复溶药品的结果分别与测试的其他固体和液体介质的趋势一致，并且表明冻干药品能够从瓶塞中浸出可测量量的物质，而复溶药品中不含有源自瓶塞的物质。
