Original Research

Evaluation of injection force of

three insulin delivery pens
T Asakura†, H Seino, M Kageyama & N Yohkoh
†Department of Clinical Pharmacy, Niigata University of Pharmacy and Applied Life Sciences,
1. Introduction 265-1 Higashizima, Akiha-ku, Niigata, 956-8603 Japan
2. Methods
Objective: Reduced injection force is among the modifications to the Next
3. Results
Generation FlexPen® (NGFP). This force was compared with two other
4. Discussion
prefilled pens: SoloStar® (SS) and KwikPen® (KP). Research design/methods:
5. Conclusions The injection force of the pens was measured, with either a BD Micro-Fine™
Expert Opin. Pharmacother. Downloaded from informahealthcare.com by Selcuk Universitesi on 01/01/15

6. Expert Opinion 31G thin-wall needle, or a NovoFine® 32G Tip extra thin wall needle attached.
Pens of each type were tested with both needles, during injection of 20 U
insulin, at speeds 3.3, 5 and 8.3 mm/s. Results: NGFP had a significantly
(p < 0.05) lower mean injection force than SS or KP, at all injection speeds,
with both needles. Injection forces (mean ± s.d.) with NGFP and the BD Micro-Fine™
31G thin-wall needle were: 8.1 ± 0.7, 10.7 ± 1.4 and 15.6 ± 0.9 N at the three
speeds, respectively. For SS, the corresponding values were: 9.2 ± 0.5, 13.3 ± 0.8
and 20.7 ± 2.4 N. For KP they were: 12.5 ± 1.6, 16.9 ± 1.2 and 24.5 ± 2.6 N.
Attached to the NovoFine® 32G Tip extra thin wall needle, the NGFP injection
forces were: 5.7 ± 0.4, 8.2 ± 0.7 and 12.7 ± 0.5 N; with SS were: 6.7 ± 0.3,
10.4 ± 2.1 and 16.3 ± 1.1 N; and with KP were: 9.1 ± 1.3, 13.1 ± 0.8 and
For personal use only.

21.6 ± 2.0 N. The injection force with NGFP was 12 – 25% lower compared
with SS and 35 – 41% lower compared with KP. Conclusions: This study shows
that NGFP has a significantly lower injection force than SS or KP.

Keywords: injection force, insulin pen, KwikPen, Next Generation FlexPen, SoloStar

Expert Opin. Pharmacother. (2009) 10(9):1389-1393

1. Introduction

Insulin pens have several benefits over the more traditional vials and syringes for
insulin injection in people with diabetes; these include improved accuracy [1-7],
flexibility and convenience [8,9], patient preference [9-14] and increased adher-
ence [8,15-17]. Improved adherence could have benefits in the management of
diabetes by helping in achieving glycaemic control [18-20].
The flexibility and convenience of pens (along with their perceived clinical
efficacy and effect on quality of life) are important factors in user preference [14].
A wide variety of design features of pens contribute to patients’ perceptions of
these factors. The force required to inject insulin (injection force) is one factor
that can influence the perception of insulin pens, as many people with diabetes
have impaired manual dexterity [21-25].
Several pens are now available and different attributes of these pens may deter-
mine which pen is chosen. Next Generation FlexPen® (NGFP; Novo Nordisk
A/S, Bagsværd, Denmark) has been developed to improve the usability of this
prefilled pen [26], and in particular, to reduce the injection force, compared with
the ‘conventional’ FlexPen®. NGFP has an injection force ∼ 30% lower than the
injection force of FlexPen [27]. The low injection force of some marketed pens

10.1517/14656560903018929 © 2009 Informa UK Ltd ISSN 1465-6566 1389

All rights reserved: reproduction in whole or in part not permitted
 Injection force of insulin pens
may be perceived as an advantage. NGFP has been shown to
have a lower injection force than one of these pens, the pre-
filled pen SoloStar® (SS; Sanofi-Aventis, Paris, France), at
several injection speeds [28]. Another prefilled pen with a low
injection force is KwikPen® (KP; Eli Lilly, Indianapolis, IN,
USA: also marketed as MirioPen). The aim of this study was
to make a head-to-head comparison with the three most
frequently used prefilled pens, NGFP, SS and KP.
2. Methods
2.1 Materials
The three pens used in this study were NGFP filled with
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Levemir® (Novo Nordisk) (insulin detemir) randomly
selected from a single lot (VP52202); SS filled with Lantus®
(Sanofi-Aventis) (insulin glargine) randomly selected from a
single lot (U002); and Humalog KP (insulin lispro) randomly
selected from a single lot (A421438DD). The needles used
were BD Micro-Fine™ 31G thin-wall 5mm needle (Becton
Dickinson, NJ, USA; lot 8094224A) and NovoFine® 32G
Tip extra thin wall 6 mm needle (Nipro-Novo Nordisk
Pharma; lot 07H19S). NGFP was imported from Denmark,
as it was not launched at the time of the study. SS and
KP were sourced through the hospital pharmacy. All
For personal use only.
injections were made into an injection cushion, which is
purported to simulate adipose tissue. All tests were performed
in a climate-controlled laboratory at 20 ± 2°C, with relative
humidity 45 ± 7.5%.
2.2 Measurement of injection force
All three pens were tested separately with both needles
(the same needle was used on each pen to avoid variation
in measured injection force caused by the flow stress of
different needles). Injection force was measured at three
different injection speeds: 3.3, 5 or 8.3 mm/s, and
10 measurements were made during the delivery of each 20
U dose. All pens were unused, and so before delivering each
dose the pen was prepared by mounting a needle and
expelling air at 2 U steps, until liquid appeared at the tip
of the needle, confirming the delivery of insulin. The
pen was then mounted on the testing machine (UTC-500:
A & D, Tokyo, Japan) to deliver the dose at the set
push-button speed.
Delivery of the first dose with each pen can require a
higher injection force owing to a running-in effect, caused
by siliconisation of the glass cartridge during its manufacture,
which causes friction between the rubber piston and the
cartridge. To allow for this, the measurement of the first
dose was excluded from the main calculations.
Mean and maximum injection force was measured for
each individual pen and means (± s.d.) were calculated for
each pen type at each injection speed. The injection force
was measured at the ‘plateau’ that occurs in the typical
injection force spectra at a displacement of 5 – 9 mm. The
1390 Expert Opin. Pharmacother. (2009) 10(9)
values for the SS and KP were compared with the NGFP
(the most widely used prefilled pen in Japan) and calculations
of significance were made using the Mann-Whitney U test
and Student t-test.
3. Results
With all three pens and with either needle, the injection
force increased with increased injection speed (Figures 1 and 2).
At all three injection speeds and with both needles, NGFP
had a significantly lower mean injection force than either
SS or KP, and KP had the highest mean injection force
(Figures 1 and 2). The injection force with all three pens was
lower when the NovoFine® 32G Tip extra thin wall needle
was used than when the BD Micro-Fine™ 31G thin-wall
needle was used.
The mean injection force (± s.d.) for NGFP, SS and KP
with the BD needle at an injection speed of 3.3 mm/s was
8.1 ± 0.7, 9.2 ± 0.5 and 12.5 ± 1.6 N, respectively; at
5 mm/s the values were 10.7 ± 1.4, 13.3 ± 0.8 and 16.9 ± 1.2
N, respectively; and at 8.3 mm/s the values were 15.6 ± 0.9,
20.7 ± 2.4 and 24.5 ± 2.6 N, respectively (Figure 1). The
maximum injection force (± s.d.) for NGFP, SS and KP with
the BD needle at an injection speed of 3.3 mm/s was 9.4 ±
0.5, 9.6 ± 0.4 N (p < 0.05 versus NGFP) and 13.0 ± 1.6 N
(p < 0.05), respectively; at 5 mm/s was 11.3 ± 1.5, 14.0 ± 0.7
N (p < 0.05) and 17.7 ± 1.1 N (p < 0.05), respectively; and
at 8.3 mm/s was 16.9 ± 0.4, 23.6 ± 1.0 N (p < 0.05) and
26.4 ± 2.4 N (p < 0.05), respectively.
The mean injection force (± s.d.) for NGFP, SS and KP
with the NovoFine® 32G Tip extra thin wall needle at
an injection speed of 3.3 mm/s was 5.7 ± 0.4, 6.7 ± 0.3
and 9.1 ± 1.3 N, respectively; at 5 mm/s the values were
8.2 ± 0.7, 10.4 ± 2.1 and 13.1 ± 0.8 N, respectively;
and at 8.3 mm/s the values were 12.7 ± 0.5, 16.3 ± 1.1
and 21.6 ± 2.0 N, respectively (Figure 2). The maximum
injection force (± s.d.) for NGFP, SS and KP with the
NovoFine® 32G Tip extra thin wall needle at an injection
speed of 3.3 mm/s was 6.6 ± 0.2, 7.1 ± 0.3 N (p < 0.05
versus NGFP) and 10.0 ± 1.7 N (p < 0.05), respectively;
at 5 mm/s was 9.1 ± 0.7, 10.9 ± 2.3 N (p < 0.05) and
13.9 ± 0.7 N (p < 0.05), respectively; and at 8.3 mm/s
was 13.2 ± 0.3, 18.0 ± 0.6 N (p < 0.05) and 23.6 ± 1.3 N
(p < 0.05), respectively.
4. Discussion
At three different injection speeds for the delivery of 20 U
insulin, using two different needle types, NGFP had a
significantly lower mean injection force than SS (by 12 – 25%)
and KP (by 35 – 41%). This confirms the low injection force
previously demonstrated with NGFP (when delivering 60 U
insulin) [27,28]. It has been reported that people with diabe-
tes prefer a lower injection force (which is particularly
important in people with impaired manual dexterity), but
 Asakura, Seino, Kageyama & Yohkoh

NGFP pens, the injection force with NGFP was 18 – 28% lower
SS than SS [28], a very similar difference to that measured in the
3.3 *
*
KP present study (despite the use of different injection speeds).
It may also have been of interest to capture data on overall
Speed (mm/s)

injection time as reported by Rissler et al. [28]. In this study,

5.0
the time to complete each dose delivery was measured with the
*
* SS and NGFP pens and showed that it took ∼ 2 – 3 s longer to
deliver a 60 U dose with SS than with NGFP at three different
injection speeds. This could be incorporated into the design
8.3 *
of any future studies.
* The study design incorporated the use of needles from two
different manufacturers because the manufacturers of insulin
0 5 10 15 20 25 30 pens recommend different needles. Both recommended needles
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Force (N) were, therefore, used on all pens. This methodology also allowed
a direct comparison of the three pens without the influence of
needle-related confounding factors.
Figure 1. Mean injection force with NGFP, SS and KP fitted
Three different injection speeds were tested, and
with BD Micro-Fine™ 31G thin-wall needle when delivering
NGFP had the lowest injection force at all three speeds.
20 U at three different injection speeds. Error bars correspond
to s.d.
It is a reasonable supposition that different patients will
* p < 0.05 compared with NGFP. depress the push-button on insulin pens at different
NGFP: Next Generation FlexPen®; SS: SoloStar®; KP: KwikPen®. speeds. Although we are not aware of published data on
the injection speeds commonly used by people with
diabetes, the lower injection force with NGFP across a
NGFP range of injection speeds from 3.3 to 8.3 mm/s suggests
For personal use only.

3.3
SS that most injections in practice would require less force
*
KP with NGFP than with SS or KP. It is interesting to note
*
that at the medium speed (5 mm/s) the injection force
Speed (mm/s)

with the NGFP was similar to that recorded with the SS

5.0 *
* force with the NGFP at the highest speed (8.3 mm/s)
8.3
0 5 10 15
Force (N)
Figure 2. Mean injection force with NGFP, SS and KP fitted
with NovoFine® 32G Tip extra thin wall needle when
delivering 20 U at three different injection speeds. Error bars
correspond to s.d.
* p < 0.05 compared with NGFP.
NGFP: Next Generation FlexPen®; SS: SoloStar®; KP: KwikPen®.
it is not known how significant these differences in injec-
tion force (as measured here) would be to the pen-user [22,23,25].
It is clear that further studies to investigate patients’
perceptions of these differences, in a clinical context, would
be beneficial.
The only previous comparison of the injection force of
NGFP and SS measured a significantly lower injection force
of 18 – 45% with NGFP [28]. However, when the same
NovoFine® 32G Tip extra thin wall needle was used on both
at the lower speed (3.3 mm/s). Likewise, the injection
was similar to that recorded for the KP at the medium
speed. It is possible that in terms of patient preference,
* the speed of injection would be a deciding factor, rather
* than injection force, by itself.
The injections were all made into an injection cushion,
20 25 which is purported to simulate adipose tissue. However, in
patients the thickness and distribution of adipose tissue
varies from one individual to another. The use of this
standardised injection medium may be considered to be one
of the limitations of this study.
We cannot draw any conclusion on the effects of injection
force on patient perception, preference and adherence from
this technical report. Future studies could assess the role of
injection force on preference. The significant patient prefer-
ence for NGFP compared with FlexPen may be a result
of this reduced injection force (because this is the main
difference between these two pens) [26,27].
5. Conclusions
There is good evidence that NGFP offers some improvements
to ‘conventional’ FlexPen, such as reduced injection force [27]
and improved colour-coding of the different insulins [26], and
overall patients prefer NGFP [26]. The proven accuracy of
FlexPen [4,6,7] is also maintained in NGFP [27]. Furthermore,

Expert Opin. Pharmacother. (2009) 10(9) 1391

 Injection force of insulin pens

this study and others show that NGFP has advantages used for insulin injection. The impact of improvements to
over SS and KP in terms of improved accuracy and reduced NGFP on outcomes of insulin therapy would be an interesting
injection force [28,29]. area for future research.

6. Expert Opinion Declaration of interest

As well as the low injection force, NGFP has a number of
attributes that could potentially drive user preference, such
as a high level of accuracy and precision [27,29], simplicity
and comfort of use [26], and a clear differentiation between
insulin types [26]. With patient preference for the method of
insulin injection being an important aspect of adherence in
diabetes management [15], the attributes of NGFP could have
an impact on adherence and, therefore, on the choice of pen
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This study was supported by an unrestricted research grant
from Novo Nordisk to Niigata University of Pharmacy. The
publication was supported by Novo Nordisk A/S (Bagsværd,
Denmark) with editorial assistance from ESP Bioscience
(Sandhurst, UK). The authors are wholly responsible for the
study design, technical measurements, analysis and scientific
evaluation, and all authors were responsible for the content
of this manuscript and approved the submitted draft.

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Affiliation
T Asakura†1, H Seino2, M Kageyama1 &
N Yohkoh1
†Author for correspondence
1Department of Clinical Pharmacy,
Faculty of Pharmaceutical Sciences
Niigata University of Pharmacy and
Applied Life Sciences,
265-1 Higashizima, Akiha-ku,
Niigata, 956-8603 Japan
Tel: +81 (0)250 25 5287; Fax: +81 (0)250 25 5287;
E-mail: asa-mac@m7.dion.ne.jp
2Seino Clinic
6-192-2 Kaisei,
Koriyama, 963-8851, Japan
1393
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For personal use only.