Microparticles and Nanoparticles Delivered in Intravenous Saline and in an Intravenous Solution of a Therapeutic Antibody Product
Microparticles and Nanoparticles Delivered in Intravenous Saline and in an Intravenous Solution of a Therapeutic Antibody Product
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DOI：
10.1016/j.xphs.2016.09.028
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发表时间：
2017-02-01
影响因子：
3.8
通讯作者：
Carpenter, John F.
中科院分区：
文献类型：
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作者：
Pardeshi, Neha N.;Qi, Wei;Carpenter, John F.
静脉(IV)输液用于很大比例的生物治疗药物的给药，包括大多数单抗产品。在这项研究中，我们测定了静脉给药溶液中的亚可见颗粒水平，以及在模拟典型临床给药方法的静脉给药设置处理后的溶液中的可见粒子水平。赫士睿和百特生产的袋装静脉盐水溶液中含有1600-8000微粒子/毫升和4-73×10(6)纳米粒子/毫升。当将免疫球蛋白稀释到静脉盐水中时，检测到3700-23,000微粒子/毫升和18-240×10(6)纳米粒子/毫升。在通过静脉注射系统处理溶液的过程中，串联过滤器去除了大部分微粒。然而，在生理盐水中仍有1-21×10(6)纳米粒/毫升，在生理盐水中稀释的免疫球蛋白中仍有7-83×10(6)纳米粒/毫升。最后，在通过在线过滤器处理的样品中，我们发现相对较大的微粒(20-60毫米)由蛋白质或聚碳酸酯组成。这些颗粒是由于聚碳酸酯的脱落和滤膜下游蛋白质膜的脱落造成的。总体而言，结果表明，即使安装了在线过滤器，也会向患者提供高水平的亚可见颗粒物，需要改进的、更有效的过滤器和低颗粒物水平的静脉注射解决方案。(C)2017年美国药剂师协会(R)。爱思唯尔公司出版，版权所有。
Intravenous ( IV) infusion is used for administration of a large proportion of biologic therapeutics, including most monoclonal antibody products. In this study, we determined the subvisible particle levels in IV solutions and after the solutions were processed with an IV administration setup that mimicked the typical clinical method of administration. IV saline in bags manufactured by both Hospira and Baxter contained 1600-8000 microparticles/mL and 4-73 x 10(6) nanoparticles/mL in solution. When IV immunoglobulin was diluted into the IV saline, 3700-23,000 microparticles/mL and 18-240 x 10(6) nanoparticles/mL were detected. During processing of the solution through the IV system, in-line filters removed most microparticles. However, there were still 1-21 x 10(6) nanoparticles/mL in IV saline and 7-83 x 10(6) nanoparticles/mL in IV immunoglobulin diluted in saline. Finally, in samples processed through in-line filters, we found relatively large microparticles ( 20-60 mm) that were composed of protein or polycarbonate. These particles resulted from shedding of polycarbonate and sloughing off of protein films downstream from the filter membrane. Overall, the results document that even with in-line filters in place, high levels of subvisible particles are delivered to patients and there is a need for improved, more effective filters and IV solutions with lower particle levels. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.