Jenke Dennis, Liu Norman, Hua Yousheng, Swanson Steven, Bogseth Roy
Baxter Healthcare Corporation, Round Lake, IL
Baxter Healthcare Corporation, Round Lake, IL.
PDA J Pharm Sci Technol. 2015 May-Jun;69(3):366-82. doi: 10.5731/pdajpst.2015.01046.
Ethanol/water mixtures are frequently used as simulating solvents in extractables studies. However, the basis for determining and justifying the right ethanol proportion in a simulating solvent for a particular drug product or solution has not been previously established.A solvent strength model has been developed in this study, based on the correlation between the levels of a model compound, di-(2-ethylhexyl) phthalate (DEHP), extracted from a reference source material, plasticized poly-(vinyl chloride) (PVC) resin, and the proportion of ethanol in ethanol/water extractions solvents. This model was established by experimentally investigating DEHP leaching and takes the form: [Formula: see text] If the level of DEHP extracted from the standard source PVC resin by a drug product is measured, then the level can be input into the above equation and the proper ethanol content of the appropriate simulating solvent can be determined.The model has been applied to certain drug products and additives used in drug products, and the proper ethanol/simulating solvents for these products have been established. Additionally, the leaching behavior revealed in this study has been established to be consistent with previously published research and a mechanism for the observed behavior has been proposed.
Although ethanol/water mixtures are frequently used as simulating solvents in extractables studies, it is difficult to establish and justify what the right proportion of ethanol is for a particular drug product. A solvent strength model has been developed based on the leaching behavior of a model compound, di-(2-ethylhexyl) phthalate (DEHP), from a reference source material, plasticized poly-(vinyl chloride) (PVC). By measuring the level of DEHP leached into a drug product from the reference source material, one can use the model to calculate the correct ethanol proportion in the simulating solvent.Using this approach, ethanol/water proportions have been obtained for certain drug products. Additionally, the leaching profiles for DEHP obtained in this study were noted to be consistent with such profiles for other extractables from the PVC reference source material and with other investigations of ethanol/water as model stimulants.
乙醇/水混合物常用于可提取物研究中的模拟溶剂。然而，此前尚未确定并论证特定药品或溶液模拟溶剂中合适乙醇比例的依据。本研究基于从参考源材料增塑聚氯乙烯（PVC）树脂中提取的模型化合物邻苯二甲酸二（2-乙基己基）酯（DEHP）的含量与乙醇/水萃取溶剂中乙醇比例之间的相关性，开发了一种溶剂强度模型。该模型通过对DEHP浸出进行实验研究建立，形式为：[公式：见原文] 如果测量了药品从标准源PVC树脂中提取的DEHP含量，那么该含量可输入上述方程，从而确定合适模拟溶剂的恰当乙醇含量。该模型已应用于某些药品及药品中使用的添加剂，并确定了这些产品合适的乙醇/模拟溶剂。此外，本研究揭示的浸出行为已被确定与先前发表的研究一致，并提出了观察到的行为的机制。
尽管乙醇/水混合物常用于可提取物研究中的模拟溶剂，但难以确定并论证特定药品合适的乙醇比例。基于模型化合物邻苯二甲酸二（2-乙基己基）酯（DEHP）从参考源材料增塑聚氯乙烯（PVC）中的浸出行为，开发了一种溶剂强度模型。通过测量参考源材料中浸出到药品中的DEHP含量，可使用该模型计算模拟溶剂中正确的乙醇比例。采用这种方法，已获得某些药品的乙醇/水比例。此外，本研究中获得的DEHP浸出曲线被指出与PVC参考源材料中其他可提取物的此类曲线以及以乙醇/水作为模型刺激剂的其他研究一致。
