On the needle clogging of staked-in-needle pre-filled syringes: Mechanism of liquid entering the needle and solidification process
| Autor: | Kewei Yang, Pierre Boillat, Robert K. Müller, Mathieu Rigollet, Christian Grünzweig, David Mannes, Frank Bamberg, M. De Bardi, T.A. Jung |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Time Factors
Materials science Drug Storage Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Clogging 03 medical and health sciences 0302 clinical medicine Pressure Composite material Drug Packaging Syringe Physical pressure Syringes Temperature Process (computing) General Medicine 021001 nanoscience & nanotechnology Mechanism (engineering) Pharmaceutical Preparations Solubility Solvent evaporation Gas pressure Needles Drug product 0210 nano-technology Biotechnology |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 128:272-281 |
| ISSN: | 0939-6411 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect