Glass Silicone Oil Free Pre-filled Syringe as Primary Container in Autoinjector.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2024-12-01 Epub Date: 2024-12-05 DOI:10.1007/s11095-024-03795-y

Xi Zhao, Yueli Chen, Hassen Hamzaoui, Xiaona Wen, Jing Song, Kaitlin Wang, Guangli Hu

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引用次数: 0

Abstract

Objective: Pre-filled syringes (PFSs) have become popular as a convenient and cost-effective container closure system for delivering biotherapeutics. However, standard siliconized PFSs may compromise the stability of therapeutic proteins due to their exposure to the silicone oil-water interface. To address this concern, silicone oil-free (SOF) glass syringes coupled with silicone-oil free plunger stoppers have been developed. This study aims to compare the impact of silicone oil-free (SOF) and siliconized syringes as primary container on protein stability and device functionality of the combination products.

Methods: The stability of proteins with different modalities was assessed in SOF and siliconized 1 mL glass syringes for up to 6 months at 5℃, 25℃, and 40℃ with levels of subvisible particles and soluble aggregate determined by micro-flow imaging (MFI) and ultra performance size-exclusion chromatography (UP-SEC). The functionality of SOF glass syringes, including break loose force, extrusion force and delivery time in autoinjectors, was evaluated at different time points during the stability study. Additionally, SOF glass syringes were filled with viscosity surrogate ranging from 1 to 90 cP to understand the impact of solution viscosity on break loose force, extrusion force, and autoinjector delivery time.

Results: SOF demonstrates compatibility with proteins and exhibited significantly low particle counts compared to siliconized PFS. SOF syringes show significantly higher break-loose and extrusion forces. However, unlike siliconized syringes where silicone oil migration increases extrusion force, no significant change in functionality was observed in SOF glass syringe during stability testing. Overall, SOF glass syringes showed great potential as an alternative package for biologics with comparable performance on functionality as siliconized PFS.

Conclusions: The combination of SOF glass and its PTFE coated stopper presents a new primary container closure system with both adequate protein stability and desired functionality features.

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无硅油预充式玻璃注射器作为自动注射器的主容器。

目的：预充式注射器（pfs）作为一种方便、经济的容器封闭系统已成为生物治疗药物输送的热门工具。然而，由于暴露于硅油-水界面，标准硅化PFSs可能会损害治疗蛋白的稳定性。为了解决这个问题，无硅油（SOF）玻璃注射器与无硅油柱塞已经开发出来。本研究旨在比较无硅油（SOF）和硅化注射器作为主要容器对组合产品蛋白质稳定性和设备功能的影响。方法：在5℃、25℃和40℃条件下，采用微流成像（MFI）和超高效粒径隔离层析（up - sec）法测定不同形态蛋白在sofl和硅化1ml玻璃注射器中长达6个月的稳定性。在稳定性研究过程中，对soff玻璃注射器在不同时间点的功能进行了评估，包括自动进样器的断裂力、挤出力和给药时间。此外，在SOF玻璃注射器中填充1 ~ 90 cP的粘度替代物，以了解溶液粘度对断裂力、挤出力和自动进样器给药时间的影响。结果：与硅化PFS相比，sofs具有与蛋白质的相容性，并且具有显著的低颗粒计数。软注射器显示出明显更高的断裂和挤压力。然而，与硅油迁移增加挤出力的硅化注射器不同，SOF玻璃注射器在稳定性测试中没有观察到明显的功能变化。总的来说，SOF玻璃注射器作为生物制剂的替代包装显示出巨大的潜力，其功能性能与硅化PFS相当。结论：SOF玻璃及其PTFE涂层塞的组合提供了一种新的初级容器封闭系统，具有足够的蛋白质稳定性和理想的功能特征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.