The syringe in a subcutaneous auto-injector may be subjected to internal pressure transients due to the normal operation of the injection mechanism. These transients are similar to transients in fluid-filled pipelines observed during water hammer events. In this paper, the effect of an air gap in the syringe and a converging section is studied experimentally and numerically in a model system which consists of a fluid-filled metal tube that is impulsively loaded with a projectile to simulate the action of the auto-injector mechanism operation. The air between the buffer and the water results in a complex interaction between the projectile and the buffer. Also, there are tension waves inside the tube due to the presence of a free surface and the motion of the buffer, and this causes distributed cavitation which, in turn, gives rise to steepening of the pressure waves. The converging section can amplify the pressure waves if the wave front is sharp, and it can enhance the collapse of bubbles. Pressures as high as 50 MPa have been measured at the apex of the cone with impact velocities of 5.5 m/s.

References

1.
Akers
,
M. J.
,
2010
,
Sterile Drug Products: Formulation, Packaging, Manufacturing and Quality
, 1st ed.,
CRC Press
,
Boca Raton, FL
.
2.
Limmroth
,
V.
, and
Gerbershagen
,
K.
,
2014
, “
Single-Use Autoinjector for Once-Weekly Intramuscular Injection of IFNβ-1a
,”
Expert Opin. Drug Delivery
,
11
(
12
), p.
1969
.
3.
Schiff
,
M.
,
Jaffe
,
J.
,
Freundlich
,
B.
, and
Madsen
,
P.
,
2014
, “
New Autoinjector Technology for the Delivery of Subcutaneous Methotrexate in the Treatment of Rheumatoid Arthritis
,”
Expert Rev. Med. Devices
,
11
(
5
), pp.
447
455
.
4.
Thompson
,
I.
, and
Lange
,
J.
,
2013
, “
Pen and Autoinjector Drug Delivery Devices
,”
Sterile Product Development: Formulation, Process, Quality and Regulatory Considerations
(AAPS Advances in the Pharmaceutical Sciences Series),
P.
Kohle
,
M.
Shah
, and
N.
Rathore
, eds.,
Springer-Verlag
,
New York
, pp.
331
356
.
5.
Lange
,
J.
, and
Thompson
,
I.
,
2013
, “
Self-Injection Devices
,”
Encyclopedia of Pharmaceutical Science and Technology
, 4th ed.,
J.
Swarbrick
, ed.,
CRC Press
,
Boca Raton, FL
, pp.
3132
3143
.
6.
Thompson
,
I.
,
2006
, “
Self-Injection Technology and Trends
,”
J. Innovations Pharm. Technol.
,
20
, pp.
60
63
.http://www.iptonline.com/articles/public/page60616263loresnonprint.pdf
7.
French
,
D.
, and
Collins
,
J.
,
2010
, “
Advances in Parenteral Injection Devices and Aids
,”
Pharmaceutical Dosage Forms: Parenteral Medications
, 3rd ed.,
S.
Nema
, and
J.
Ludwig
, eds.,
Informa Healthcare
, Boca Raton, FL, pp.
71
85
.
8.
Veilleux
,
J.-C.
, and
Shepherd
,
J.
,
2018
, “
Pressure and Stress Transients in Autoinjector Devices
,”
Drug Delivery Transl. Res.
,
8
(5), pp. 1238–1253.
9.
Fry
,
A.
,
2014
, “
Injecting Highly Viscous Drugs
,”
Pharm. Technol.
,
38
(
11
), epub.http://www.pharmtech.com/injecting-highly-viscous-drugs
10.
Stout
,
D.
, and
Vilivalam
,
V.
,
2009
, “
Plastic Prefilled Syringes: A Better Fit for Autoinjector Systems
,”
Pharm. Technol.
,
2009
(
Suppl. 6
), epub.http://www.pharmtech.com/plastic-prefilled-syringes-better-fit-autoinjector-systems
11.
Wiggert
,
D. C.
, and
Tijsseling
,
A.
,
2001
, “
Fluid Transients and Fluid-Structure Interaction in Flexible Liquid-Filled Piping
,”
ASME Appl. Mech. Rev.
,
54
(
5
), pp.
455
481
.
12.
Wylie
,
E.
, and
Streeter
,
V.
,
1993
,
Fluid Transients in Systems
,
Prentice Hall
,
Englewood Cliffs, NJ
.
13.
Watters
,
G. Z.
,
1984
,
Analysis and Control of Unsteady Flow in Pipelines
, 2nd ed.,
Butterworths
,
Stoneham, MA
.
14.
Bergant
,
A.
,
Simpson
,
A.
, and
Tijsseling
,
A.
,
2006
, “
Water Hammer With Column Separation: A Historical Review
,”
J. Fluids Struct.
,
22
(2), pp. 135–171.
15.
Inaba
,
K.
, and
Shepherd
,
J. E.
,
2010
, “
Dynamics of Cavitating Flow and Flexural Waves in Fluid-Filled Tubes Subject to Axial Impact
,”
ASME
Paper No. PVP2010-25989.
16.
Shepherd
,
J. E.
, and
Inaba
,
K.
,
2010
, “
Shock Loading and Failure of Fluid-Filled Tubular Structures
,”
Dynamic Failure of Materials and Structures
,
G.
Ravichandran
and
Y.
Rajapakse
, eds.,
Springer-Verlag
, Boston, MA, pp.
153
190
.
17.
Hallquist
,
J. O.
,
2016
,
LS-DYNA: Theory Manual
,
Livermore Software Technology Corporation
,
Livermore, CA
.
18.
Wu
,
Z.
,
Zong
,
Z.
, and
Sun
,
L.
,
2014
, “
A Mie-Grüneisen Mixture Eulerian Model for Underwater Explosion
,”
Eng. Comput.
,
31
(
3
), pp.
425
452
.
19.
Kojima
,
T.
,
Inaba
,
K.
,
Takahashi
,
K.
,
Triawan
,
F.
, and
Kishimoto
,
K.
,
2017
, “
Dynamics of Wave Propagation Across Solid-Fluid Movable Interface in Fluid-Structure Interaction
,”
ASME J. Pressure Vessel Technol.
,
139
(
3
), p.
031308
.
20.
Liepmann
,
H. W.
, and
Roshko
,
A.
,
2001
,
Elements of Gasdynamics
,
Dover Publications
,
Mineola, NY
.
21.
Bitter
,
N. P.
, and
Shepherd
,
J. E.
,
2013
, “
On the Adequacy of Shell Models for Predicting Stresses and Strains in Thick-Walled Tubes Subjected to Detonation Loading
,”
ASME
Paper No. PVP2013-97148.
22.
Sturtevant
,
B.
, and
Kulkarny
,
V. A.
,
1976
, “
The Focusing of Weak Shock Waves
,”
J. Fluid Mech.
,
73
(
4
), pp.
651
671
.
23.
Veilleux
,
J.-C.
,
Maeda
,
K.
,
Colonius
,
T.
, and
Shepherd
,
J. E.
,
2018
, “
Transient Cavitation in Pre-Filled Syringes During Autoinjector Actuation
,”
Tenth International Symposium on Cavitation
(
CAV
), Baltimore, MD, May 14–16.http://shepherd.caltech.edu/EDL/publications/reprints/CAV2018_Veilleux_et_al.pdf
24.
Brennen
,
C. E.
,
2013
,
Cavitation and Bubble Dynamics
,
Cambridge University Press
,
Cambridge
, Cambridge, UK.
25.
Veilleux
,
J.-C.
, and
Shepherd
,
J.
, 2018, “
Dampers and Methods for Performing Measurements in an Autoinjector
,” U.S. Patent No. 20180015224.
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