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

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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

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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: ladick@mmm.com