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Assessment of Forces in Intradermal Injection Devices: Hydrodynamic Versus Human Factors

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Stijn Verwulgen
Stijn Verwulgen
Stijn Verwulgen
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Koen Beyers
Koen Beyers
Koen Beyers
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Timothi Van Mulder at University of Antwerp
Timothi Van Mulder
Thomas Peeters at University of Antwerp
Thomas Peeters
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Abstract and Figures

PurposeThe force that has to be exerted on the plunger for administering a given amount of fluid in a given time, has an important influence on comfort for the subject and usability for the administrator in intradermal drug delivery. The purpose of this study is to model those forces that are subject-independent, by linking needle and syringe geometry to the force required for ejecting a given fluid at a given ejection rate. Material and Methods We extend the well-known Hagen-Poiseuille formula to predict pressure drop induced by a fluid passing through a cylindrical body. The model investigates the relation between the pressure drop in needles and the theoretic Hagen-Poiseuille prediction and is validated in fifteen needles from 26G up to 33G suited for intradermal drug delivery. We also provide a method to assess forces exerted by operators in real world conditions. ResultsThe model is highly linear in each individual needle with R-square values ranging from 75% up to 99.9%. Ten out of fifteen needles exhibit R-square values above 99%. A proof-of-concept for force assessment is provided by logging forces in operators in real life conditions. Conclusions The force assessment method and the model can be used to pinpoint needle geometry for intradermal injection devices, tuning comfort for subjects and usability for operators.
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RESEARCH PAPER
Assessment of Forces in Intradermal Injection Devices:
Hydrodynamic Versus Human Factors
Stijn Verwulgen
1
&Koen Beyers
2,3
&Timothi Van Mulder
2,4,5
&Thomas Peeter s
1
&Steven Truijen
6
&Francis Dams
1
&
Vanessa Vankerckhoven
2,5
Received: 28 December 2017 / Accepted: 26 March 2018 / Published online: 18 April 2018
#Springer Science+Business Media, LLC, part of Springer Nature 2018
ABSTRACT
Purpose The force that has to be exerted on the plunger for
administering a given amount of fluid in a given time, has an
important influence on comfort for the subject and usability
for the administrator in intradermal drug delivery. The pur-
pose of this study is to model those forces that are subject-
independent, by linking needle and syringe geometry to the
force required for ejecting a given fluid at a given ejection rate.
Material and Methods We extend the well-known Hagen-
Poiseuille formula to predict pressure drop induced by a fluid
passing through a cylindrical body. The model investigates the
relation between the pressure drop in needles and the theo-
retic Hagen-Poiseuille prediction and is validated in fifteen
needles from 26G up to 33G suited for intradermal drug
delivery. We also provide a method to assess forces exerted
by operators in real world conditions.
Results The model is highly linear in each individual needle
with R-square values ranging from 75% up to 99.9%. Ten out
of fifteen needles exhibit R-square values above 99%. A proof-
of-concept for force assessment is provided by logging forces in
operators in real life conditions.
Conclusions The force assessment method and the model can
be used to pinpoint needle geometry for intradermal injection
devices, tuning comfort for subjects and usability for
operators.
KEY WORDS flow rate model .human factors .injection
devices .injection force .needle geometry
ABBREVIATIONS
ID Intradermal
IM Intramuscularly
SC Subcutaneously
INTRODUCTION
The skin represents the largest organ of the human body (1). It
consists of three layers: the epidermis, preventing chemicals
and micro-organisms entering the body, the dermis playing a
role in immunological surveillance, and the hypodermis or
sub-cutis that consists mainly of subcutaneous fat providing
insulation, restoring trauma and providing energy reserve
(2–4). The skin is considered of particular interest for drug
delivery due to its unique immunogenic properties and en-
hanced pharmacokinetics. To date vaccines are mainly ad-
ministered intramuscularly (IM) with syringe and needle.
Literature reports non-inferior immunogenic responses upon
intradermal (ID) delivery (5,6). Comparison of ID and SC
administration in type 1 diabetes showed a significant reduc-
tion of pain and superior pharmacokinetics. A more than 40%
reduction in onset and 24% reduction in offset time could
support closed loop therapy based on ID insulin administra-
tion (7,8).
Traditionally, ID injections are mainly achieved via the
Mantoux technique: a hypodermic needle is inserted almost
parallel, at 5–10 degrees, into the subject’s skin to assure that
*Stijn Verwulgen
Stijn.verwulgen@uantwerpen.be
1
Department of Product Development, Faculty of Design Sciences
University of Antwerp, Campus Mutsaard, Ambtmanstraat 1
2000 Antwerpen, Belgium
2
Novosanis, Wijnegem, Belgium
3
Voxdale, Wijnegem, Belgium
4
Department of Nursing and Midwifery, University of
Antwerp, Wilrijk, Belgium
5
Vaccine & Infectious Disease Institute, University of
Antwerp, Wilrijk, Belgium
6
Department Rehabilitation Sciences and Physiotherapy, University of
Antwerp, Wilrijk, Belgium
Pharm Res (2018) 35: 120
https://doi.org/10.1007/s11095-018-2397-2
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Finally, the characterization of the injection process would not be complete without a measurement of the pressure generated during and after the injection. While previous reports have measured injection forces and pressures under various conditions (Allmendinger et al., 2015;Verwulgen et al., 2018), these measurements have never been paired with images of the injection site itself to fully characterize the injection process. The goals of this study, therefore, were to develop simultaneous CT imaging and pressure measurement methods to characterize largevolume subcutaneous injections and to assess the effects of HLN on these injections. ...
... This could also be due to differences in the viscosity of the injection as well as differences in the strain of minipig used, along with the small difference in injected volumes. Our injection pressure measurements were performed using an inline sensor split off from the injection line via 3-way stopcock which is different than those previously reported (Allmendinger et al., 2015;Verwulgen et al., 2018) where a force sensor attached to the syringe pump was used. While this resulted in a slower rise of pressure early in the part of the injection (cf Allmendinger et al., 2015; Figure 2), the maximum pressure values we observed were still consistent with those reported after converting to force (Newtons), and when comparing similar injection rates and viscosities. ...
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