M. De Bardi , R. Müller , C. Grünzweig , D. Mannes , P. Boillat , M. Rigollet , F. Bamberg , T.A. Jung , K. Yang
{"title":"插针式预充注射器的针头堵塞:液体进入针头的机理和凝固过程","authors":"M. De Bardi , R. Müller , C. Grünzweig , D. Mannes , P. Boillat , M. Rigollet , F. Bamberg , T.A. Jung , K. Yang","doi":"10.1016/j.ejpb.2018.05.006","DOIUrl":null,"url":null,"abstract":"<div><p>Staked-in-needle prefilled syringes (SIN-PFS) are widely used for the parenteral administration of drug product solutions. During stability studies, clogging of the injection needle was observed in syringes filled with concentrated antibody solution. A prerequisite for this phenomenon is that liquid has entered the needle. In this study, we characterized the mechanism causing the entry and movement of liquid in the needle using neutron imaging without manipulating the container closure integrity of the syringe. The gas pressure difference between inside and outside of the syringe was identified as the major cause of liquid movement. The influence of external factors, such as temperature fluctuation and physical pressure on the stopper, were tested and were confirmed to have a relevant impact on the processes of liquid entering and moving inside the injection needle. In a second step, the solidification process of the liquid segments inside the needle via solvent evaporation was further investigated, and the process was found to be dependent on storage time, environmental climate and interaction between the drug product solution and the needle surface. The presence of air/liquid segments was identified as a further factor for the stochastic behavior of needle clogging. For the first time, this fundamental mechanism behind the needle clogging issue was investigated in depth and the results will help to reduce the defect rate for clogged SIN-PFS products.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejpb.2018.05.006","citationCount":"9","resultStr":"{\"title\":\"On the needle clogging of staked-in-needle pre-filled syringes: Mechanism of liquid entering the needle and solidification process\",\"authors\":\"M. De Bardi , R. Müller , C. Grünzweig , D. Mannes , P. Boillat , M. Rigollet , F. Bamberg , T.A. Jung , K. Yang\",\"doi\":\"10.1016/j.ejpb.2018.05.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Staked-in-needle prefilled syringes (SIN-PFS) are widely used for the parenteral administration of drug product solutions. During stability studies, clogging of the injection needle was observed in syringes filled with concentrated antibody solution. A prerequisite for this phenomenon is that liquid has entered the needle. In this study, we characterized the mechanism causing the entry and movement of liquid in the needle using neutron imaging without manipulating the container closure integrity of the syringe. The gas pressure difference between inside and outside of the syringe was identified as the major cause of liquid movement. The influence of external factors, such as temperature fluctuation and physical pressure on the stopper, were tested and were confirmed to have a relevant impact on the processes of liquid entering and moving inside the injection needle. In a second step, the solidification process of the liquid segments inside the needle via solvent evaporation was further investigated, and the process was found to be dependent on storage time, environmental climate and interaction between the drug product solution and the needle surface. The presence of air/liquid segments was identified as a further factor for the stochastic behavior of needle clogging. For the first time, this fundamental mechanism behind the needle clogging issue was investigated in depth and the results will help to reduce the defect rate for clogged SIN-PFS products.</p></div>\",\"PeriodicalId\":12024,\"journal\":{\"name\":\"European Journal of Pharmaceutics and Biopharmaceutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2018-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/j.ejpb.2018.05.006\",\"citationCount\":\"9\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Pharmaceutics and Biopharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0939641118301929\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pharmaceutics and Biopharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0939641118301929","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
On the needle clogging of staked-in-needle pre-filled syringes: Mechanism of liquid entering the needle and solidification process
Staked-in-needle prefilled syringes (SIN-PFS) are widely used for the parenteral administration of drug product solutions. During stability studies, clogging of the injection needle was observed in syringes filled with concentrated antibody solution. A prerequisite for this phenomenon is that liquid has entered the needle. In this study, we characterized the mechanism causing the entry and movement of liquid in the needle using neutron imaging without manipulating the container closure integrity of the syringe. The gas pressure difference between inside and outside of the syringe was identified as the major cause of liquid movement. The influence of external factors, such as temperature fluctuation and physical pressure on the stopper, were tested and were confirmed to have a relevant impact on the processes of liquid entering and moving inside the injection needle. In a second step, the solidification process of the liquid segments inside the needle via solvent evaporation was further investigated, and the process was found to be dependent on storage time, environmental climate and interaction between the drug product solution and the needle surface. The presence of air/liquid segments was identified as a further factor for the stochastic behavior of needle clogging. For the first time, this fundamental mechanism behind the needle clogging issue was investigated in depth and the results will help to reduce the defect rate for clogged SIN-PFS products.
期刊介绍:
The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics.
Topics covered include for example:
Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids)
Aspects of manufacturing process design
Biomedical aspects of drug product design
Strategies and formulations for controlled drug transport across biological barriers
Physicochemical aspects of drug product development
Novel excipients for drug product design
Drug delivery and controlled release systems for systemic and local applications
Nanomaterials for therapeutic and diagnostic purposes
Advanced therapy medicinal products
Medical devices supporting a distinct pharmacological effect.