Intradermal Delivery
Innovations in Pharmaceutical Technology issue 50. © Samedan Ltd. 2014
Keywords
Intradermal injectors
Transdermal patch
Hollow microneedle delivery
Patient-centric benefits
Established via hypodermic syringe
in the 1850s, intramuscular and
subcutaneous injections have a
long-standing
history and are
still used today by
millions around the
world. However,
an estimated 10%
of all Americans
are needle-phobic,
and an even higher percentage of
individuals claim their dislike of
needles as the reason for foregoing
medical treatment (1). In addition,
conventional syringes are also
challenged by the potential of an
accidental needlestick injury to the
dose administrator, or limitations –
in some cases – of administration by
a clinician rather than in a patient’s
home setting.
A common alternative to
intramuscular and subcutaneous
injections for those looking to avoid
needles is transdermal delivery,
which uses an adhesive patch
to deliver medication. This form
of delivery presents advantages
over oral methods too, including
improved efficacy due to its ability
to avoid first-pass metabolism.
Additionally, it can reduce
By Lisa Dick at 3M Drug Delivery Systems
With the rapid growth of the biologics market, companies are researching new delivery methods to meet these products’ unique formulation requirements. Along with subcutaneous or intravenous methods, a growing number are considering intradermal administration as an alternative direction
Pointing the Way©
Fel
ix P
erga
nde
– Fo
tolia
.com
iptonline.com
consists of a drug reservoir and
flow path between the reservoir
and the hollow microneedles.
It also includes the means to
pressurise the drug reservoir
and insert the microneedles,
due to the microneedle density
(see Figure 2) (3).
Key PointsWhen considering intradermal
delivery, there are a few factors
pharmaceutical and biotech
companies should keep in mind:
● Formulation compatibility with
an intradermal delivery method
– this can be tested during early
feasibility studies
● Desired volume of the delivered
formulation – some intradermal
delivery systems can only
deliver between 0.5mL and
1mL of the liquid formulation,
although 3M's hollow
microneedle system is intended
for delivery up to 2mL
● Strength of the microneedles
upon delivery
● Required drug delivery
timeframe
● Overall performance and
additional benefits – such as
a pharmacokinetics profile
or improved bioavailability,
compared with subcutaneous
or intravenous routes of
administration
Competitive LandscapeThe expanded delivery range
of biologics has challenged
companies to be innovative
in developing new drug
administration methods. With the
advancements made thus far, it
is hard to believe that only a few
years ago, the first intradermal
injector to reach the market was
introduced by Becton Dickinson:
BD Soluvia™ Microinjection System.
It is a microinjection system for
intradermal delivery, consisting
of a single needle coupled with
a prefillable injection system for
vaccines or drugs (3). The device is
capable of injecting about 0.1mL
of flu vaccine.
side-effects in certain therapeutic
areas and maintain a steady blood
level of medication.
A number of advancements
have been made since the
transdermal patch’s introduction
in 1975, but this delivery method
still has limitations. The natural
barrier properties of skin can be
an issue itself. Most transdermal
drugs must be lipophilic, but also
possess some hydrophilic character,
in order to permeate through the
lipid cell layers and deeper into
the skin where interstitial fluid
is present.
Microneedle CapabilitiesIntradermal delivery via
microneedle technology may
expand the range of large molecules
that could otherwise prove difficult
to deliver. Microneedle technology
actively transports drugs through
the outer stratum corneum to the
dermis. The needles are narrower
and shorter than a pen injector,
putting them out of the range of
many nerve endings. The smaller
needles result in a more patient-
friendly administration method.
There are several technologies
in development intended for
intradermal delivery. 3M's hollow
microneedle delivery system, for
example, is designed for intradermal
delivery of liquid formulations,
including biologics and other
small molecules. This technology
has the flexibility to deliver up
to hundreds of milligrams of
high-value formulations of
proteins, resulting in direct
absorption of the drug into the
systemic circulation, by-passing
the digestive and hepatic portal
systems (2). Capable of holding
a high volume of formulation,
it should be supported by an
appropriate solution cartridge,
where the formulation sits prior
to delivery (see Figure 1).
3M's hollow microstructured
transdermal system (hMTS)
Figure 1: An example of hollow microneedle technology
Image: © 3M Company 2014. 3M is a trademark of 3M Company
Figure 2: An example of polymer microneedles that are approximately 1,000 micron tall, used in hMTS
Image: © 3M Company 2014. 3M is a trademark of 3M Company
iptonline.com
or three-needle device with
silicon microneedle arrays, and
has a sharp tip with a side hole
for rapid injection of 0.5mL
volume (4)
● 3M’s hMTS is designed for
self-administration of liquid
formulations. The device is
comprised of 12 polymer
microneedles in an array that is
intended for delivery of between
0.5mL and 2mL of fluid
These options give biopharma
companies looking for the most
suitable intradermal delivery
method a basis of comparison to
determine which delivery option
best meets their needs.
Patient Preference In addition to formulation-design
advancements, microneedles
offer a patient-friendly alternative
for the administration of injectable
therapies. Easy handling for self-
administration may increase
the patient’s convenience and
potentially reduce associated
healthcare costs from the
necessity of administering a
drug in a clinical setting. As an
example, the hMTS features a
textured grip which is designed
for patients with dexterity issues.
For treatments suitable for
self-administration, switching
from intravenous administration
to intradermal delivery could
mean avoiding an extra trip to a
doctor’s office for an injection
or outpatient hospital facility
for intravenous therapy. This
provides convenience for the
patient, along with the potential
to offer additional pharmaco-
economic benefits.
New AlternativeAs pharma companies continue to
explore alternatives to traditional
injections, microneedle technology
is ideally suited for intradermal
delivery, addressing the need
for effective administration of
biologics, including proteins
and peptides.
NotesBD Soluvia is a trademark and product of Becton Dickinson.MicronJet is a trademark and product of NanoPass.HUMIRA is a registered trademark and product of AbbVie.
References1. Williams JP and Lednar W, The
American Journal of Managed Care 8, S145, 2002
2. Harvey A et al, Microneedle-based intradermal delivery enables rapid lymphatic update and distribution of protein drugs, Pharmaceutical Research 28: pp107-116, 2011
3. Burton S, Microneedle delivery systems, An Innovation Showcase: Advanced Drug Delivery Approaches for Small and Large Molecules, Lecture conducted from 3M Innovation Center, St Paul, Minnesota, June 2014
4. DebioJect: Successful and accurate ID injection, 2014. Visit: www.debiotech.com/newsite/page/index.php?page=product_01&id =1&id_prod=47
5. Dohmeier D, Microneedle-based drug delivery: Clinical data and manufacturing readiness, Lecture from the International Conference on Microneedles, Baltimore, Maryland, May 2014
Other companies are also continuing
to work towards developing and
commercialising hollow microneedle
technology, including NanoPass,
Debiotech and 3M:
● The Micronjet Needle™,
developed by NanoPass, is a
single-use microneedle-based
device that is intended for use
with a standard syringe and
may be compatible to inject
biologicals, vaccines or small
molecules
● The DebioJect, launched by
Debiotech, is a single needle
Put to the Test
To support the benefits of intradermal delivery, a human clinical study was recently conducted by 3M (2013), in which the performance of intradermal delivery via its hollow microneedle system versus a subcutaneous auto-injector for delivery of HUMIRA® (adalimumab) in a Phase 1 clinical study was determined (5). A full 40mg dose of the drug in 0.8mL volume was first given through hollow microneedles to a group of 12 women, aged 18-55, then the HUMIRA auto-injector was used to provide the same dose and volume to a second group of subjects.
The full dose of HUMIRA was successfully delivered via the hMTS, during which delivery time was monitored, skin tolerability was assessed, and blood samples were collected. When the blood samples for both groups of subjects were analysed, it was found that the pharmacokinetic profiles were a close match, validating hollow microneedle technology and its potential as an alternative drug delivery method.
For treatments suitable for self-administration, switching from intravenous administration to intradermal delivery could mean avoiding an extra trip to a doctor’s office for an injection or outpatient hospital facility for intravenous therapy
Dr Lisa Dick is the Microstructured Transdermal System Technical Manager for 3M Drug Delivery Systems in St Paul, Minnesota, US. She earned her PhD in Chemistry from Northwestern University and did postdoctoral research
at Princeton University, focusing on protein and peptide chemistry. Her research interests include development of inhalation and transdermal drug delivery systems. Email: [email protected]
Top Related