Xi Zhao, Yueli Chen, Hassen Hamzaoui, Xiaona Wen, Jing Song, Kaitlin Wang, Guangli Hu
{"title":"无硅油预充式玻璃注射器作为自动注射器的主容器。","authors":"Xi Zhao, Yueli Chen, Hassen Hamzaoui, Xiaona Wen, Jing Song, Kaitlin Wang, Guangli Hu","doi":"10.1007/s11095-024-03795-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2319-2329"},"PeriodicalIF":3.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Glass Silicone Oil Free Pre-filled Syringe as Primary Container in Autoinjector.\",\"authors\":\"Xi Zhao, Yueli Chen, Hassen Hamzaoui, Xiaona Wen, Jing Song, Kaitlin Wang, Guangli Hu\",\"doi\":\"10.1007/s11095-024-03795-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":20027,\"journal\":{\"name\":\"Pharmaceutical Research\",\"volume\":\" \",\"pages\":\"2319-2329\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11095-024-03795-y\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11095-024-03795-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/5 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Glass Silicone Oil Free Pre-filled Syringe as Primary Container in Autoinjector.
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.
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.
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