Interaction of preservatives with contact materials during filling and storage of parenteral liquid formulations

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2024-11-26 DOI:10.1016/j.ejps.2024.106971
Paul Gottschalk , Patrick Schlossbauer , Lucas Schleicher, Katrin Lindner, Ingo Presser, Maximilian Wittmann
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Abstract

Silicone tubing is a frequently used material in pharmaceutical filling processes for parenteral formulations, as its characteristics like flexibility, chemical resistance and easy handling make it particularly suitable for these purposes. This study investigated the time-dependent interaction of phenol and m-cresol with silicone tubing and other broadly applied contact materials used during the filling and transport processes of parenteral formulations. Phenol losses could be observed after incubation in silicone tubing, depending on the inner diameter (ID). This has been demonstrated for process interruptions of up to 120 min. A loss of 40 % could be observed for a small ID of 3.2 mm which can be found close to filling needles, and up to 12 % for larger tubes with an ID of 9.5 mm commonly used for sterile filtration and transport processes. Analysis of tubes with varying ID revealed a linear relationship between the decrease of phenol and the surface-to-volume ratio. m-cresol showed an even more pronounced loss in silicone tubing. Fluorinated polymers and thermoplastic elastomers were also analyzed, and no loss of phenol and m-cresol was observed. Pumping tests revealed that shear forces in peristaltic pumps led to strong particle formation in selected tubing. A strong increase in particle concentration was observed in thermoplastic elastomers, particularly in PharMed® BPT tubing. In contrast, the C-Flex® tubing demonstrated minimal particle formation. Fluorinated polymers are not compatible with peristaltic pumps, which is why they were not analyzed regarding pumpability. Although silicone tubes are not impervious to preservatives such as phenol, they did not generate particles when pumped.

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肠外液体制剂在灌装和储存过程中防腐剂与接触材料的相互作用。
硅胶管是肠外制剂灌装过程中经常使用的一种材料,因为它具有柔韧性、耐化学腐蚀性和易于处理等特点,特别适用于这些用途。本研究调查了苯酚和间甲酚与硅胶管及其他广泛应用于肠外制剂灌装和运输过程的接触材料之间随时间变化的相互作用。根据硅胶管的内径(ID),在硅胶管中培养后可观察到苯酚的损失。这已在长达 120 分钟的工艺中断中得到证实。内径为 3.2 毫米的小硅胶管(可在灌装针头附近找到)的苯酚损失率为 40%,而内径为 9.5 毫米的大硅胶管(常用于无菌过滤和运输过程)的苯酚损失率则高达 12%。对不同内径的管子进行的分析表明,苯酚的减少量与表面体积比之间呈线性关系。对含氟聚合物和热塑性弹性体也进行了分析,没有发现苯酚和间甲酚的损失。泵送测试表明,蠕动泵中的剪切力导致选定管材中形成大量颗粒。在热塑性弹性体中,尤其是在 PharMed® BPT 管材中,观察到颗粒浓度大幅增加。相比之下,C-Flex® 管中的颗粒形成极少。含氟聚合物与蠕动泵不兼容,因此没有对它们的泵送性进行分析。虽然硅胶管不耐受苯酚等防腐剂,但在泵送时也不会产生颗粒。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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