Pressure and stress transients in autoinjector devices
- 162 Downloads
Spring-actuated autoinjectors delivering viscous drug solutions resulting from large drug concentrations require large spring forces which can create high peak pressures and stresses within syringes. The high peak pressures and stresses can lead to device failure. Measurements with a suite of novel instrumentation and analysis using numerical simulation explain the peak pressures and peak stresses as originating from mechanical impacts between moving components, the large acceleration of the components, and surprisingly, the production of tension waves in the liquid resulting in cavitation. The presence and intensity of cavitation depend on relative timing between the pressurization and the acceleration of the syringe, which, in turn, depend on the size and location of an air gap inside the syringe. We show that production of localized but very high pressures can result from shock wave focusing in the conical section of the syringe.
KeywordsAutoinjector Viscous drug solution High-concentration drug solution Pressure waves Stress waves Cavitation Shock focusing
We would like to thank Julian Jazayeri for his help in performing some of the experiments. We would also like to thank Julian Jazayeri and Dr. Bruce Eu for their support and fruitful discussions.
This work is sponsored by Amgen through the Caltech-Amgen Research Collaboration Agreement for Chem-Bio-Engineering Awards.
Compliance with Ethical Standards
J.C. Veilleux is listed as a co-author on a U.S. patent application related to the content of this work. J.E. Shepherd is listed as a co-author on a U.S. patent application related to the content of this work, and has consulted for Amgen in 2014 and 2015.
- 1.Lange J, Thompson I. Self-injection devices. Encyclopedia of pharmaceutical science and technology. 4th edn. Taylor & Francis; 2013. P. 3132–3143.Google Scholar
- 2.Akers MJ. Sterile drug products: formulation, packaging, manufacturing and quality. Drugs and the pharmaceutical sciences series. 1st edn. Boca Raton: CRC Press; 2010.Google Scholar
- 3.Adler M. Challenges in the development of pre-filled syringes for biologics from a formulation scientist’s point of view. American pharmaceutical review. 2012. http://www.americanpharmaceuticalreview.com/. Accessed 6 April 2018.
- 4.French D, Collins J. Advances in parenteral injection devices and aids. In: Nema S, Ludwig J, editors. Pharmaceutical dosage forms: parenteral medications. 3rd edn. Informa Healthcare; 2010. P. 71–85.Google Scholar
- 6.Stout D, Vilivalam V. Plastic prefilled syringes: a better fit for autoinjector systems. Pharmaceutical Technology 2009; 2009(6).Google Scholar
- 7.Fry A. Injecting highly viscous drugs. Pharm Technol. 2014; 38(11).Google Scholar
- 8.Kundu P, Cohen I, Dowling D. Fluid mechanics, 5th. Oxford: Academic Press; 2012.Google Scholar
- 9.Thompson I. Self-injection technology and trends. Journal of Innovations in Pharmaceutical Technology 2006;20:60–63.Google Scholar
- 10.Thompson I, Lange J. Pen and autoinjector drug delivery devices. In: Kohle P, Shah M, Rathore P, editors. Sterile product development: formulation, process, quality and regulatory considerations. AAPS advances in the pharmaceutical sciences series. American Association of Pharmaceutical Scientists; 2013. P. 331–356. https://doi.org/10.1007/978-1-4614-7978-9_13.
- 12.Wilkins J, Simpson I. Mathematical modeling for faster autoinjector design. (2012). http://www.drug-dev.com/. Accessed 6 April 2018.
- 13.Brennen C. Cavitation and bubble dynamics. Oxford engineering science series. Cambridge: Oxford University Press; 1995.Google Scholar
- 14.Franc J, Michel J. Fundamentals of cavitation. Fluid mechanics and its applications series. Netherlands: Springer; 2006.Google Scholar
- 16.Wylie E, Streeter V, Suo L. Fluid transients in systems prentice hall. 1993.Google Scholar
- 17.Veilleux JC, Shepherd J. Dampers and methods for performing measurements in an autoinjector. US Patent Application 20180015224. Filed July 2017. Published January 2018.Google Scholar
- 18.Jones N. Structural impact. Cambridge: Cambridge University Press; 1997.Google Scholar
- 19.Hibbeler R. Mechanics of materials. 8th edn. Singapore: Prentice Hall; 2011.Google Scholar
- 20.Kolsky H. Stress waves in solids. London: Oxford University Press; 1953.Google Scholar
- 22.Callister WD, Rethwisch DG. Materials science and engineering : an introduction. Hoboken: Wiley; 2014.Google Scholar
- 23.McLellan GW, Shand EB. 1984. Glass engineering handbook. 3rd edn. McGraw-Hill;Google Scholar
- 24.Hallquist JO. 2006. LS-DYNA : THEORY MANUAL. Livermore Software Technology Corporation, Livermore, California (USA). Latest edn. http://www.lstc.com/manuals.
- 26.Pierce A. Acoustics : an introduction to its physical principles and applications. 2nd edn. Acoustical Society of America; 1989.Google Scholar