• Patchless Transdermal Drug Delivery ... - Ecn5.com ecn5

VOLUME 3 NUMBER 2 Exclusively for the delivery of pharmaceuticals through the skin
MARCH 2011
• Patchless Transdermal Drug Delivery
• Transdermal Formulation of Peptide and
Protein Drugs

www.transdermalmag.com March 2011 Volume 3 Number 2
FoRMulATioN TEchNiquES
DEPARTMENTS
On the cover: Dermal electroporation using a
minimally invasive device (MID-II) results in robust
green fluorescent protein (GFP) and red fluorescent
protein (RFP) expression following intradermal delivery
of GFP and RFP reporter plasmids. This device offers a
safe, tolerable, and efficient method to administer
DNA vaccinations in a prophylactic setting and
potentially represents an important new option for
improved DNA-vaccine delivery in vivo. Courtesy of
Inovio Pharmaceuticals, San Diego, California, USA.
www.inovio.com
Patchless Transdermal Drug Delivery (TDD) 5
Bozena B Michniak-Kohn, Rutgers-The State University of New Jersey
Kishore R Shah, Polytherapeutics, Inc
On the Transdermal Formulation of Peptide and Protein Drugs 12
Xiaorong Shen and David Jones
Primera Analytical Solutions
Industry news 2 Calendar 16
Research news 3 People news C3
Issue focus 5 Supplier news C3
Transdermal (ISSN 1948-5824 online ISSN 1948-3600 print) is published six times a year in January, March, May, July,
September, and November by CSC Publishing, Inc., 1155 Northland Drive, Saint Paul, MN 55120.

EdiTORiAl
Peggy Wright
Editor
pwright@cscpub.com
PROducTiOn And ART
Maria novak
Production Manager
mnovak@cscpub.com
harry Myers
Assistant Production Manager
hmyers@cscpub.com
linda Rost
Production Coordinator
lrost@cscpub.com
christopher Myers
Prepress Manager
cmyers@cscpub.com
ciRculATiOn
Aileen hough
Circulation Manager
ahough@cscpub.com
sarah highum
Assistant Circulation Manager
shighum@cscpub.com
Judie hadley
Circulation Assistant
jhadley@cscpub.com
BusinEss
Richard R. cress
Publisher
rcress@cscpub.com
heather fitch
Administrative Manager
hfitch@cscpub.com
Melinda cress
Acctg/Oper Manager
lcress@cscpub.com
PhilAdElPhiA OfficE
800 West State St., Suite 103
Doylestown, PA 18901
+1 215 340-6988
FAX: +1 215 340-6989
e-mail: segenolf@cscpub.com
w w w . t r a n s d e r m a l m a g . c o m
PuBlishing OfficE
1155 Northland Drive
St. Paul, MN 55120
+1 651 287-5600
FAX: +1 651 287-5650
e-mail: transdermal@cscpub.com
cindy fischer
Acctg/Oper Administrator
cfischer@cscpub.com
Michelle R. Robinson
Acctg/Mktg Coordinator
mrobinson@cscpub.com
liz dorry
Web site Coordinator
ldorry@cscpub.com
Kelly Weyandt
Web and Online Development
kweyandt@cscpub.com
AdvERTising
Marybeth stewart
West Coast & Mid-Atlantic Sales
Manager
mstewart@cscpub.com
+1 541 318-4657
Maggie Johnson
Midwest & Southeastern Sales
Manager
mjohnson@cscpub.com
+1 651 287-5600
steve Egenolf
Eastern Sales Manager
segenolf@cscpub.com
+1 215 340-6988
Jan lee
Midwest Sales Manager
jlee@cscpub.com
+1 513 583-9768
Kevin clohesey
Upstate New York, Canada,
& Western Sales Manager
kclohesey@cscpub.com
+1 651 287-5600
Bonnie Kaye
National Accounts Manager
bkaye@cscpub.com
+1 651 213-1400
cincinnATi OfficE
887 Murle Lane
Loveland, OH 45140
+1 513 583-9768
FAX: +1 513 583-9736
e-mail: jlee@cscpub.com
Transdermal • MARCH 2011
Editorial
Advisory Board
Ajay K. Banga,
Mercer University
James Birchall,
Cardiff University
Joke Bouwstra,
Leiden University
Somesh Choudhury,
Noven Pharmaceuticals, Inc.
Lawrence A. Hill,
Watson Pharmaceuticals
Bozena Michniak-Kohn,
Rutgers University and New
Jersey Center for Biomaterials
Reinhard Neubert,
Martin-Luther-University (MLU)
Halle-Wittenberg
Danyi Quan,
Xel Pharmaceuticals
Michael S. Roberts,
University of Queensland and
University of South Australia
Audra Stinchcomb,
University of Kentucky
Phillip Wertz,
University of Iowa
Thean Yeoh,
Pfizer Inc.
Technical
Advisory Board
Kishore R. Shah,
Polytherapeutics, Inc.
©2011 by CSC Publishing, Inc. All rights reserved.
Published six times per year. No part of
this publication may be reproduced or transmitted
in any form or by any means without
written permission from the publisher.
Transdermal assumes no responsibility for statements
or opinions of editorial contributors or
advertisers.
Go to www.transdermalmag.com to apply for
your free subscription.
1

2
MARCH 2011 • TransDermal
Industry news
Eisai finalizes
Japanese license
agreement
Tokyo, Japan — Eisai finalized an
exclusive license agreement with
Teikoku Seiyaku, which will re -
search, develop, and market a
new transdermal formulation of
Aricept for treatment of Alz -
heimer’s disease in Japan. Eisai
will supply the active pharmaceutical
ingredients for clinical and
nonclinical use.
Prosolus
Pharmaceuticals plans
to relocate
Philadelphia, Pennsylvania,
USA — According to the South
Florida Business Journal, Prosolus
Pharmaceuticals plans to relocate
to Doral, Florida in Miami-Dade
County. The company, only a year
old, has licensed a transdermal
system and wants to develop a
5,000-square-foot manufacturing
and product-development center
there.
Commercial launch of
Prelude is on track
Franklin, Massachusetts, USA —
Echo Therapeutics’ partner, Ferndale
Pharma Group, received
comments from the US FDA on
the 510(k) submission of the Prelude
SkinPrep System that both
companies deemed minor and
consistent with expectations. Echo
anticipates that the planned date
for commercial launch of the product
will remain on track, pending
FDA clearance.
Alcohol Monitoring
Systems files patent suit
Littleton, Colorado, USA — Alco-
hol Monitoring Systems (AMS)
has filed a lawsuit claiming that
BI, Incorporated has infringed
multiple patents with their TAD
(Transdermal Alcohol Detection)
system. AMS manufactures a
trans dermal alcohol monitoring
system, SCRAMx (Secure Continuous
Remote Alcohol Monitor),
which samples a subject’s perspiration
for the purposes of monitoring
alcohol consumption.
Rutgers University
launches center for
dermal research
Piscataway, New Jersey, USA —
On March 3, 2011, the Center for
Dermal Research at Rutgers University
held its inaugural meeting.
Dr Bozena Michniak-Kohn, PhD,
leads the center. The university
created the center to provide professional
networking opportunities
for its paid industrial members
as well as opportunities for
research collaborations with the
Laboratory for Drug Delivery,
which Michniak-Kohn heads.
Skinvisible signs
feasibility agreement
Las Vegas, Nevada, USA — Skinvisible
Pharmaceuticals signed an
agreement with Novartis Pharma
AG to assess the technical feasibility
of a topical formulation of an
undisclosed com pound using its
Invisicare polymer delivery system.
The agreement includes an
option for the two companies to
enter into a future, exclusive licen -
sing agreement that would in -
clude a licensing fee and royalties
based on sales.
Transdel
Pharmaceuticals
explores strategic
alternatives
La Jolla, California, USA —
Transdel Pharmaceuticals is ex -
ploring strategic alternatives
with two investment banks,
Amer ican Med Tech Advisors
and ESC Advisors, a division of
KEMA Partners. These alternatives
could include, but are not
limited to, partnering or other
collaborative agreements, a
merger, equity or debt financing,
or sale of the company.
Actavis voluntarily
recalls transdermal
Fentanyl
Hafnarfirdi, Iceland — Actavis
issued a voluntary recall of 18 lots
of its 25 mcg Fentanyl patch after
finding one defective lot that
caused the medicine to release
too quickly into the bloodstream.
Apogee Technology
resumes OTC trading
Norwood, Massachusetts, USA
— Apogee Technology resumed
trading on the Over-the-Counter
(OTC) board under the symbol
ATCS.OB.
NICE guidance
recommends Exelon
patch
Basel, Switzerland — The Na -
tional Institute for Health and
Clinical Excellence (NICE) guidance
TA1111 recommended
Novar tis Pharmaceuticals UK’s
Exelon transdermal patch as a
cost-effective option for treatment
of mild-to-moderate Alz -
heimer’s disease.
TransPharma changes
name of transdermal
system
Lod, Israel — TransPharma Medical
changed the name of its drug

delivery system from ViaDerm to
ViaDor. The change occurred in
part to break the association of
TransPharma’s drug delivery system
with other products carrying
the name ViaDerm.
BA Research acquires
Hill Top Research
Miamiville, Ohio, USA — BA
Research, part of the Cliantha
Group, acquired Hill Top Re -
search. All current clinical sites in
North America and India will continue
in full operation going forward.
Hill Top will continue as Hill
Top Re search in North America.
Echo Therapeutics
receives $5.5M
Franklin, Massachusetts, USA
— Echo received $5.5 million in
new financing in a deal that its
majority shareholder, Platinum
Montaur Life Sciences LLC, led.
The company will use the funds
to develop new products, move
clinical studies forward, and draw
upon for working capital and
general corporate purposes. The
agreement includes private stock
placements, netting the company
approximately $2.5 million, and a
binding commitment for another
$3 million.
Research news
FDA approves
Fentanyl patch
St. Louis, Missouri, USA — The
US FDA approved Covidien’s
ANDA for its Fentanyl Transdermal
System (FTS) patch. Its patch
is a generic alternative to Johnson
& Johnson’s branded Duragesic
patch. FTS is an opioid analgesic
indicated in opioid-tolerant pa -
tients for management of persistent,
moderate-to-severe chronic
Transdermal
Contract Manufacturing
cGMP
FDA - Drug, Device,
Food, Cosmetics
EU Compliant
Japanese Certified
ISO 9001:2008
ISO 13485:2003
DEA Registered
Schedule III – V
Manufacturer of
Controlled Substances
SoluStrip soluble film converting
for buccal transdermal delivery
TransDermal • MARCH 2011
Active and Passive transdermal
converting
�Finished patch or component
�Reservoir and matrix
Experience with ATDD technologies
�Iontophoresis
�Microneedles
�Heat-activated
�Dermabrasion
Snapplicator unit dose
packaging for transdermal
gels & ointments
Visit us at INTERPHEX Booth 1271
Tapemark
1-800-535-1998
www.tapemark.com
Write an article for
Transdermal
Technical professionals write our
articles for technical professionals.
See technical article guidelines at
www.transdermalmag.com for
information on the types of articles
we are looking for.
Contact:
Peggy Wright, Editor
Tel. +1 651 698-2760
E-mail: pwright@cscpub.com
3

4
MARCH 2011 • TransDermal
pain. Covidien expects to launch
the patch in the USA in 25mcg/
hr, 50mcg/hr, 75mcg/hr, and
100mcg/hr strengths.
PLEASE–FSH patch provides
first successful
IVF pregnancy
Ruggell, Liechtenstein — A
woman conceived successfully
after being implanted with a fertilized
oocyte (egg cell) and re -
ceiving treatment with Pantec
Biosolutions’ FSH (follicle stimulating
hormone) patch subsequent
to skin microporation with
the company’s proprietary
P.L.E.A.S.E. (Painless Laser Epidermal
System) device. The pregnancy
is the first to occur using
the technology.
Inovio and University
of Southampton begin
vaccine study
Blue Bell, Pennsylvania, USA
and Southampton, UK — Inovio
Pharmaceuticals obtained regulatory
approval for a Phase 2 clinical
trial that the University of
Southampton will run. The study
will use Inovio’s automated,
ELGEN 1000 vaccine-delivery
device and will evaluate a DNA
vaccine that the university developed
to treat chronic myeloid
leukemia and acute myeloid
leukemia. Leukaemia and Lymphoma
Research (LLR) and the
Efficacy and Mechanisms Evaluation
(EME) program, which the
UK Medical Research Council
funds and the UK National Institute
for Health Research manages,
will provide financial support.
Alvogen launches
transdermal delivery
system
Parsippany, New Jersey, USA —
Alvogen introduced an AB-1rated
nitroglycerin transdermal
delivery system. The hypoallergenic,
transparent patches are
available in 30-count cartons and
four dosage strengths, including
0.1, 0.2, 0.4, 0.6 mg/hr.
BioSante receives
orphan-drug status for
vaccine
Lincolnshire, Illinois, USA —
The US FDA granted orphandrug
status for BioSante Pharmaceuticals’
potential skin-cancer
vaccine. The company also has
received orphan-drug status for
other vaccines for pancreatic cancer,
acute myeloid leukemia, and
chronic myeloid leukemia.
Purdue Pharma
releases Butrans
transdermal system
Stamford, Connecticut, USA —
Purdue Pharma’s Butrans (bupre -
nor phine) Transdermal System
CIII is now available by prescription.
The drug is indicated for the
management of moderate-tosevere
chronic pain in patients
requiring an around-the-clock
opioid analgesic for an extended
period of time. Butrans is the first
opioid analgesic that continuously
releases buprenorphine for
seven days.
Alliqua completes
study for pain patch
New York, New York, USA —
Alliqua, formerly HepaLife Technologies,
successfully completed
an initial study for its transdermal
pain patch. In the comparative
dissolution study, its profile
was favorable when compared to
the current leading product for
treating postherpetic neuralgia
(PHN) pain. Alliqua now will
start the next developmental
stage, including in-vitro testing.
Foamix starts Phase 2
clinical trial
Rehovot, Israel — Foamix en -
rolled the first patient in a Phase
2 trial of its Topical Minocycline
Foam. The study aims to demonstrate
efficacy and safety in
patients suffering from Rosacea.
Skin-penetration studies demonstrated
a high occurrence of the
drug in the viable layers of the
skin and also revealed that the
drug is not delivered transdermally,
indicating that its topical
application will not involve any
systemic adverse effects.
FDA accepts Zelrix
NDA for filing
Conshohocken, Pennsylvania,
USA — NuPathe received notice
that the US FDA accepted the
company‘s Zelrix NDA, submitted
on October 29, 2010, for filing.
The company expects the FDA to
complete its review of the NDA
by August 29, 2011. Zelrix is the
first-ever submission to the FDA
of a transdermal patch for the
treatment of migraine.
FDA approves Fortesta
gel
Newark, Delaware, USA — The
US FDA approved Endo Pharmaceuticals’
Fortesta gel for treatment
of low testosterone, also
known as hypogonadism. The
gel comes in a metered-dose
pump that delivers the correct
dose per complete depression.
Endo ex pects to introduce the gel
in the USA in early 2011.

TransDermal • MARCH 2011
Patchless Transdermal Drug Delivery (TDD)
Bozena B Michniak-Kohn, Rutgers-The State University of New Jersey
Kishore R Shah, Polytherapeutics, Inc
We can trace the advent of transdermal
drug delivery to the FDA’s approval and
commercialization of scopolamine (1979)
and nitroglycerin (1981) patches. Since then, companies
have marketed many transdermal products
worldwide, and transdermals have become a multibillion-dollar
industry. Some of the advantages of
transdermal drug delivery include:
1. A reproducible and prolonged drug-delivery rate
2. Elimination of hepatic first-pass metabolism
3. Minimization of undesirable side effects
4. Increased convenience for and compliance by
patients
5. Rapid termination of drug therapy when desired
Despite these advantages, the barrier function of the
skin, and its irritation and sensitization by many
drugs and certain patch components, provide the
principal impediments to a wider use of transdermal
drug delivery. To some extent, patchless TDD in
the form of topically applied gels, creams, lotions, or
solutions can overcome the limitations of the skin
barrier by application of the drug formulation to a
much larger area of skin than is possible with plastic
patches.
Formulators can use patchless TDD to elicit a therapeutic
effect within tissues near the site of product
application and/or to distribute the drug throughout
the body using the circulatory system. Patchless
delivery may be suitable for treatment of various
indications, such as pain, hormone replacement therapy,
contraception, overactive bladder, CNS disorders,
male or female sexual dysfunction, and smoking
cessation.
Key advantages of patchless transdermal products
include:
• The potential for expanding the scope of trans-
dermal delivery to drugs requiring significantly
higher dosages than possible with patches
• Flexibility of dosing
• Reduction in skin irritation due to lack of
occlusion
• Lack of irritation from patch components such as
adhesives
• Ease of manufacture
• Cost effectiveness
• Cosmetic elegance
The deficiencies of the patchless TDD in contrast to
patches may include:
• Some variability in precision of dosing
• Lack of suitability for drugs having a high skinpermeation
rate, such as fentanyl and clonidine
• A narrow therapeutic window
• Lack of retention of the drug and enhancer at the
site of application
Formulation Considerations
Dosage forms for patchless TDD can be clear solutions,
gels, or emulsions. The formulator selects the
form with an emphasis on its spreadability on skin,
drying time, cosmetic feel, and acceptability to users.
A mixture of water and alcohol is often a good
medium for the preparation of a solution or gel. A
lower alkyl alcohol, such as ethanol or isopropanol,
helps to solubilize the drug. Polymeric thickeners
can adjust the viscosity of the solution for optimum
handling and spreadability. An emulsion (oil-inwater
or water-in-oil) is a useful medium for drugs
that are hydrophobic and poorly soluble in hydroalcoholic
medium. In an emulsion, the drug is solubilized
in the oil phase. Key ingredients for the preparation
of such emulsions include oils, waxes,
emulsifiers, and emollients.
5

6
MARCH 2011 • TransDermal
Excipients for TDD formulations should be nontoxic,
nonirritating, and nonsensitizing to skin, even upon
repeated application to the same site. The transdermal
composition may use different excipients
depending on the dosage form. Excipients may
include solvents for the drug, thickeners, preservatives,
anti-oxidants, chelating agents, fragrances, etc.
A key ingredient for a patchless TDD formulation is
the skin-permeation enhancer, which facilitates
delivery of a therapeutically required dosage of the
drug. Some of the common enhancers include oleic
acid, dimethyl isosorbide, lauryl lactate, dimethyl
sulfoxide, decyl methyl sulfoxide, ethoxydiglycol,
N-methyl 2-pyrrolidone, and isopropyl myristate. A
review by Danyi Quan, et al provides a detailed discussion
of enhancers for TDD [1, 2]. Many enhancers
cause skin irritation when used at higher concentrations.
Therefore, a balance between drug-permeation
enhancement and skin safety is important in optimizing
the formulation.
One of the key issues with patchless TDDs is retention
of the drug and enhancer at the site of application.
Lack of retention for the desired duration of
time is a common problem. Nature designed the
skin to shed materials adhering to it. Loss of an
applied dose also can occur by transfer to other
objects, such as articles of clothing, or other people.
The loss results in an inadequate therapeutic effect
and a shorter duration of pharmacological activity
for the drug. In addition, transfer of a drug, such as
testosterone, to others by touch is a particularly sensitive
issue pertaining to safety of the product.
An appropriate film-forming polymeric delivery system,
which can serve as a matrix for the drug and
enhancers, can address some of these issues; however,
the use of a polymer delivery system for TDD has its
own challenges. Skin is a living substrate; that is, it
breathes, perspires, stretches, and contracts. The
formed film must accommodate the various functions
of the skin during different activities and environmental
conditions, such as temperature and humidity.
It must be bioadherent and possess viscoelastic properties,
breathability, and moisture-vapor permeability
similar to skin. In the absence of such characteristics,
the film tends to feel uncomfortable or tight and peels
and flakes during use. The net result is inadequate
wear time and loss of efficacy.
Another consideration is possible crystallization of
the drug on the skin when the applied formulation
dries. Other critical issues that formulators need to
address in patchless TDD development include the
hydrolytic and oxidative stability of the drug in
aqueous or hydroalcoholic medium, pH effects, and
cosmetic acceptability.
Commercial Approaches to Patchless
TDD Products
Acrux, Vivus, Ther-Rx
Acrux (www.acrux.com.au) initially acquired its
technology — discovered by B Finnin, B Reid, and
T Morgan — from Monash University in Australia.
Sunscreens have used its ACROSS ® enhancer octisalate
for a long time at higher doses. It is a known,
safe, nonirritating formulation and allows the passage
of drugs across the barrier layer of the skin.
Acrux has placed the ACROSS enhancer in a
Metered Dose Transdermal System ® (MDTS), allowing
application of a pre-set dose of a drug. The system
also creates a patchless reservoir in the skin that
can deliver drugs for various indications for human
and veterinary use. Vivus (www.vivus.com) is the
licensee in the USA for Acrux’s testosterone spray
for women, trademarked as Luramist ® . Another
ACROSS product, Evamist ® , is a 1.7% estradiol topical
spray for systemic transdermal delivery of the
hormone (Ther-Rx, www.ther-rx.com).
Biosante, Antares Pharma, Azur Pharma
Biosante Pharmaceuticals (www.biosantepharma
.com) is a company specializing in products for
female sexual-health and oncology. The lead is
LibiGel ® , a transdermal testosterone gel for treatment
of female sexual dysfunction. Antares Pharma
(www.antarespharma.com), Biosante’s partner, is
developing it. It is in Phase 3 clinical development
under an FDA Special Protocol Assessment. Biosante
intends to submit the LibiGel NDA in 2011 for potential
approval by the FDA in 2012.
Azur Pharma (www.azurpharma.com) in Ireland is
a private pharmaceutical company focused on the
Central Nervous System (CNS) and the health of
women. Azur is marketing Elestrin ® , which they
acquired from Biosante, in the USA. It is an estradiol
gel for the treatment of menopausal vasomotor
symptoms.

Novavax, Abbot, Auxilium
Researchers initially developed micellar nanoparticle
technology in the mid-1990s. Novavax (www.nova
vax.com ) further developed, patented, and marketed
the first product using this approach, Estrasorb ® , a
transdermal lotion launched in 2003 [3]. This technique
uses a multiphasic nanoemulsion consisting of
one or two active ingredients, a solvent (often
ethanol), a stabilizer (often a nonionic surfactant), oil,
and an aqueous medium. These emulsions can incorporate
both water-soluble and poorly water-soluble
drugs and can accommodate both crystalline and
amorphous drugs. Formulators have achieved drug
loading of up to 20% (w/w). These lotions behave like
patchless patches and are highly stable formulations;
for example, Estrasorb has a shelf life of three years
at room temperature.
Androsorb ® is a topical testosterone formulation
based on micellar nanoparticle technology
(Novavax, Inc.).
Other topical testosterone products include Androgel
® (Abbott, www.abbott.com), which is a regular
or metered-dose formulation [4], and Testim ® , a
hydroalcoholic gel (Auxilium Pharmaceuticals,
www.auxilium.com). These products do not use
micellar nanoparticle technology.
Antares Pharma
In early 2010, Antares Pharma and the Population
Council announced very promising outcomes from
a dose-finding, Phase 2 clinical trial for a contraceptive
gel that contains the new, synthetic progestin
nestorone and estradiol formulated in Antares
Pharma’s Advanced Transdermal Delivery (ATD)
gel system [5, 6]. They conducted the open-label,
crossover study on 18 women at three sites, evaluating
the effect of the gel on ovulation suppression in
normal women of fertile age. The ATD gel is a clear
formulation that dries quickly on the skin and leaves
no residue. The technology uses a combination of
permeation enhancers to achieve sustained transdermal
drug delivery.
Antares Pharma also developed a transdermal, oxybutynin
gel formulation, its Anturol ® gel, delivered
using a metered dose pump [5]. The drug has
antimuscarinic and antispasmodic effects on smooth
muscle and treats incontinence in overactive bladders.
Two dose strengths are under investigation, 56
TransDermal • MARCH 2011
and 84 mg, and the pump allows dose titration.
Studies have indicated that approximately 16% of
adults are affected by an overactive bladder, and it
is particularly a problem in women and the elderly.
Kennelly, who tested the ATD, reported that transdermal
delivery of oxybutynin (gel) significantly
improved cognitive tolerability when compared to
an orally administered drug [7].
BioChemics, Vaso Active Pharmaceuticals
BioChemics’ technologies (www.biochemics.com)
include VALE ® (Vaso-Active Lipid Encapsulated)
and PENtoCORE ® (intradermal delivery), which
Vaso Active Pharmaceuticals (www.vasoactive.us)
commercialized [8, 9]. Patients use VALE as a patchless
cream or gel with dose control for targeted and
systemic delivery of small molecules. When applied
to the surface of skin, the formulation vanishes in
about one minute. An example is Osteon ® , which
delivers menthol (analgesic) for the temporary relief
of minor aches and pains of muscles and joints associated
with arthritis, sprains, strains, and simple
back pain [10]. The inactive ingredients of the gel are
deionized water, isopropanol, olive oil, propylene
glycol, eucalyptus oil, sodium alginate, cetyl alcohol,
glyceryl stearate, kelp extract, marshmallow extract,
allantoin, and xanthan gum. AR Extreme ® Pain
Relieving Lotion provides temporary relief from
pain from minor sports injuries, and TERMIN8 ®
treats athlete’s foot and provides relief for burning,
cracked, and itchy feet. Both of these formulations
use the PENtoCORE technology.
Mika Pharma
Established in 1994 for development of products for
the dermal and buccal markets, in 1995 MIKA
Pharma (www.mika-pharma.de) was the first company
worldwide to introduce a stable, topical liposomal
product (liposomal MIKA heparin spray).
Brunner et al reported on a MIKA spray gel formulation
with diclofenac, comparing it to oral Voltaren
in 12 healthy males [11]. The spray gel consisted of
water, isopropyl alcohol, and propylene glycol as
basic solvents and soy bean lecithin, ethanol, disodium
phosphate dodecahydrate, sodium dihydrogen
phosphate dehydrate, peppermint oil, and
ascorbyl palmitate as excipients. Patients sprayed it
on the skin, and the alcoholic components slowly
evaporated, leaving behind a low viscous gel that
stuck to the skin. Using microdialysis to evaluate
7

8
MARCH 2011 • TransDermal
pharmacokinetic parameters, the authors concluded
that the MIKA formulation exhibited low systemic
availability and produced effective diclofenac concentrations
equivalent to or better than the oral
dosage form. Other researchers conducted studies
using the MIKA topical liposomal technology: a) a
heparin spray used to treat superficial venous
thrombosis [12, 13] and b) topical delivery of plasmid
DNA to skin [14].
NexACT, MacroChem
NexMed, a specialty CRO with a pipeline of products
based on the NexACT ® technology, recently
changed its name (September 2010) to Apricus Biosciences
(www.apricusbio.com) and moved from
New Jersey to California in the USA [15, 16]. Its technology
is based on permeation enhancers that affect
the fluidization of lipids in cellular membranes. An
example of one of the compounds is dodecyl 2-(N,
N-dimethylamino)-propionate. Formulators can use
this technology topically, but as a recent preclinical
study showed, also can deliver insulin and other
drugs with larger molecular weights, such as Taxol,
subcutaneously in a depot-like fashion (slow re -
lease). Delivery occurs over 24 hours from a singledose
formulation. Recent investigations by Michniak-Kohn’s
lab at Rutgers University have shown
the potential use of this technology in transbuccal
delivery [17].
MacroChem, which Access Pharmaceuticals
acquired (www.accesspharma.com), developed
SEPA (Soft Enhancer of Percutaneous Absorption)
based on dioxolane chemistry, which they have
shown improves drug permeation through the skin.
Diani et al published an example of the enhancement
of activity, showing that 2-n-nonyl-1, 3-dioxolane
augments hair-growth effects of topically
applied minoxidil in the balding stump-tail-macaque
model [18].
Watson Pharmaceuticals
Watson Pharmaceuticals (www.watson.com) markets
Gelnique ® (oxybutynin chloride) gel 10%, which
is indicated for overactive bladder. It is formulated in
an alcohol-based gel containing alcohol, glycerin,
hydroxypropylcellulose, sodium hydroxide and
purified water. The patient receives the formulation
in a sachet that must be used immediately upon
opening due to evaporation of the alcohol.
BHR Pharma
BHR Pharma (www.bhr-pharma.com) has developed
a transdermal estradiol gel for the palliative treatment
of vasomotor side effects in men undergoing androgen-deprivation
therapy (ADT) for pros tate cancer
and advanced androgen-sensitive carcinoma of the
prostate. Located in Herndon, Virginia, USA, BHR
Pharma is a wholly owned subsidiary of Besins
Healthcare (www.besins-healthcare.com), a Belgian
company, and an affiliate of Ascend Therapeutics
(www.ascendtherapeutics.com), Besins’ pharmaceutical
sales and marketing entity in the USA.
BHR’s technology involves the Enhanced Hydroalcoholic
Gel ® (EHG) that Besins pioneered and commercialized
in 1975. Other products include Estrogel
® (www.estrogel.com), which is a clear and
colorless topical gel containing estradiol 0.06% for
treatment of menopausal symptoms and which is
available in a dosing pump or tube, and Progestogel
® , a 1% progesterone hydroalcoholic gel used to
treat breast pain and tenderness.
Transdel Pharma
Ketotransdel ® is a novel cream containing 10% ketoprofen,
recommended for acute soft tissue injuries
(sprains and strains). A 2010 Phase 3 study in 364
patients suggested that Ketotransdel is effective over
placebo and did not produce any severe side effects.
Researchers detected only minimal levels of ketoprofen
in the blood of the volunteers, supporting the
fact that low concentrations were absorbed systemically
[19]. Transdel (ww.transdelpharma.com)
focuses primarily on topical drug delivery, and the
Transdel technology facilitates the dissolution of the
API and enhances the passage of the drug across the
barrier of the skin.
Novartis, Endo Pharmaceuticals
Voltaren ® is a diclofenac sodium gel that contains
10mg/g of drug with the following excipients:
ammonia, carbomer homopolymer Type C, isopropyl
alcohol, mineral oil, polyoxyl 20 cetostearyl
ether, propylene glycol, and water [20]. Endo Pharmaceuticals
(www.endo.com) markets Novartis
Consumer Health’s product for relief of pain caused
by osteoarthritis of joints, such as knees and hands
(www.novartis.com). Patients apply the gel using a
dosing card that is supplied with the medication to
ensure the correct dose of diclofenac.

Nuvo Research, Covidien, King
Pharmaceuticals
Pennsaid ® contains diclofenac sodium 1.5 % w/w as
a topical solution with glycerin, propylene glycol,
ethanol, purified water, and a skin-penetration
enhancer, dimethyl sulfoxide [21, 22]. Nuvo Research
(www.nuvoresearch.com), formerly Dimethaid, manufactures
the product, and Covidien (www.covidien.com)
markets it in the USA under license from
Nuvo. In November 2009, the FDA approved Pennsaid
in the USA (originally launched in Canada),
where it is one of three products for osteoarthritis. The
other two are Voltaren ® gel (discussed previously) and
the Flector ® patch, which contains 1.3% diclofenac
sodium and is a product of King Pharmaceuticals
(www.kingpharm.com).
Esba Laboratories
Lidocaine hydrochloride topical gels are available
from various manufacturers. An example is Topicaine
® from Esba Laboratories (www.esbalabs.com)
[23]. This formulation contains 40 mg of lidocaine in
a gel composed of water, ethanol (35% w/w), glycerin,
jojoba oil, aloe vera oil, glyceryl monolaurate,
benzyl alcohol, carbomer 940, and EDTA-ethylenediaminetetraacetic
acid. Patients apply it topically
for relief of pain, and it provides analgesia in the skin
by reversibly blocking the flux of sodium ions
through the neuronal membranes.
AlphaRx
A Canadian company, AlphaRx (www.alpharx.com),
launched its Colloidal Lipid Dispersion (CLD) technology,
which provides percutaneous enhancement
of topically applied drugs. In addition, formulators
can combine this product with polymers and adhesives
for patch development and transdermal drug
delivery [24]. The Flexogan BCD ® (Bioadhesive Colloidal
Dispersion) series of products marketed in
Canada uses this technology for arthritis and muscle
and joint pain. The formulation consists of highly dispersed
oil droplets encapsulating natural menthol
and camphor. The droplet size is less than one micron,
and the formulation is nongreasy and allows a much
higher availability of the active ingredient.
Embil Pharmaceuticals
Embil Pharmaceuticals in Turkey (www.embil.com)
has patented a novel formulation, the Sulidin ® nime-
TransDermal • MARCH 2011
sulide LPS Gel [25]. The drug is indicated for osteo -
arthritis, rheumatoid arthritis, periarthritis, and posttraumatic
or acute musculoskeletal disorders. The
LPS (Lamellar Penetration System) is based on the
idea of using components of the skin structure as the
delivery system. The lamellar hydrophobic structure
both protects and facilitates the delivery of the API
into the skin.
Polytherapeutics
PharmaDur ® (www.pharmadur.com) is a graft
copolymer delivery system designed to address
issues with polymeric delivery systems discussed
above under “Formulation Considerations.” It has
been commercially available over the last few years
under that trade name. Kishore Shah first reported
on PharmaDur and related graft copolymers for
mucosal and skin applications [26]. PharmaDur
polymer combines hydrophilic and hydrophobic
structural moieties (Figure 1).
The copolymer exhibits a combination of bioadhesive
and controlled-release properties because of its
unique structural characteristics [27]. When a patient
applies a dermatological vehicle, such as a cream,
lotion, or gel formulated with the PharmaDur polymer,
the vehicle forms an imperceptible and invisible
hydrogel film, a virtual patch. The PharmaDur polymer
film is nontacky and nongreasy, has a very
smooth feel, does not exhibit flaking or skin stretchiness,
and is breathable. It is characterized by excellent
bioadhesion to skin and exhibits controlled
release of both hydrophobic and hydrophilic molecules.
Because PharmaDur polymer is very hydro -
Figure 1
PharmaDur Graft Copolymer
R – alkyl radical
n, m, x, y, & z – positive integers having unspecified different
large values
9

10
MARCH 2011 • TransDermal
philic, it also helps to moisturize the skin, an added
benefit.
PharmaDur film on the skin serves as a matrix for
the drug and other nonvolatile excipients for the
product formulation. The skin retains the polymer
film and the drug contained therein for 24+ hours,
and the film provides continuous release of the drug
by a process of diffusion for transdermal delivery to
the body (Figure 2). The formed polymer film is not
removed by perspiration or articles of clothing or
transferred by touch. Thus, it functions as a virtual
patch without the limitations of plastic patches.
Formation of an invisible hydrogel patch for time
release of medications is an attractive concept for the
Figure 2
Schematic Diagram of PharmaDur Virtual
Patch on Skin
Figure 3
Comparison of Flux of Caffeine with Oleic Acid
Formulations (controls) and with Added 2%
PharmaDur Polymer
consumer. A cosmetically elegant and invisible virtual
patch is a unique concept for transdermal delivery
of drugs, such as nonsteroidal, anti-inflammatory
drugs (NSAIDs) for systemic activity. The
virtual patch provides the following key advantages:
• Delivers drugs requiring a high dosage or those
with low skin permeability effectively since
patients can apply the product over a large area of
skin (~ 300 to 500 cm2).
• Provides all-day, sustained therapeutic efficacy
with a once-a-day application due to its long-lasting
retention on skin, which also improves convenience
for and compliance by consumers.
• Reduces undesirable side effects due to avoidance
of peaks and valleys in systemic drug concentrations
as are typically found with oral drug
administration.
• Delivers many drugs that are not suitable for
transdermal administration using conventional
plastic patches and semisolid dosage forms.
Furthermore, our studies have shown that the Pharma
Dur polymer acts synergistically with skin-penetration
enhancers in maximizing the rate of transdermal
drug delivery. For example, Michniak et al
(28) previously reported the effect of PharmaDur
polymer on transdermal permeation of caffeine in
the presence of the enhancer oleic acid. The re -
searchers studied the skin-permeation rate of caffeine
with and without the PharmaDur polymer,
using human cadaver skin and Franz diffusion cells.
The presence of the PharmaDur polymer almost
doubled the skin-permeation rate of caffeine compared
to that of the control formulation consisting of
caffeine and oleic acid (Figure 3).
The researchers postulate that the PharmaDur polymer
film provides controlled release of both caffeine
and the enhancer, thereby maximizing the enhancement
in the caffeine permeation rate.
Conclusion
Patchless TDD is emerging as a convenient and
patient-friendly means for extending the scope of
transdermal delivery of drugs. Several new products
and technologies using this approach for eliciting
both local and systemic therapeutic effects have
emerged in the last decade.

References
1. Quan D, Hui X, and Maibach, H. Chemical enhancement
of transdermal drug delivery systems-Part I. Transdermal. March
2010, 2(2):5-10.
2. Quan D, Hui X, and Maibach H. Chemical enhancement
of transdermal drug delivery systems-Part II. Transdermal. March
2010, (2(3):15-20.
3. Lee, RW, Shenoy DB, Sheel R. Micellar nanoparticles:
Applications for topical and passive transdermal drug delivery.
Chapter 2 in Handbook of Non-invasive Drug Delivery. Toronto,
Canada: Elsevier, 2010, pp 37- 58.
4. Androgel information at
www.drugs.com/androgel.html, accessed 1/19/2011.
5. Information on Anturol gel at
antarespharma.com/pipeline/anturol-gel, accessed 1/19/2011.
6. Contraceptive gel study, www.popcouncil.org/mediacenter/newsreleases/2010_antarespharma/,
accessed 12/03/2010.
7. Kennelly, MJ. A comparative review of oxybutynin chloride
formulations: Pharmacokinetics and therapeutic efficacy in
overactive bladder. Reviews in Urology. 2010 Winter, 12(1):12-19.
8. Biochemics’ company information,
www.biochemics.com, accessed 1/19/2011.
9. Vasoactive product information, www. vasoactive.us,
accessed 1/19/2011.
10. Osteon lotion information, www.osteonlotion.com,
accessed 1/19/2011.
11. Brunner M, Dehghanyar P, Seigfried B, Martin W, Menke
G, Muller M. Favourable dermal penetration of diclofenac after
administration to the skin using a novel spray formulation. British J
Clin Pharmacol. 2005 Nov, 60(5):573-577.
12. Gorski G, Szopinski P, Michalak J et al. Liposomal
heparin spray: A new formula in adjunctive treatment of superficial
venous thrombosis. Angiology. 2005 Jan-Feb, 56, 9-17.
13. Katzenschlager R, Ugurluoglu A, Minar E, Hirschi M.
Liposomal heparin-spraygel in comparison with subcutaneous low
molecular weight heparin in patients with superficial venous
thrombosis: A randomized, controlled, open multicenter study. J
Kardiol. 2003, 10(9): 375-378.
14. Meykadeh N, Mirmohammadsadegh A, Wang Z, Basner-
Tschakarjan E, Hengge UR. Topical application of plasmid DNA to
mouse and human skin. J Mol Med, 2005 Nov, 83(11): 897-903.
15. NexACT technology, www.newsmedical.net/news/20100318/NexACT-technology-demonstratesability-to-deliver-Taxol-subcutaneously,
accessed 12/03/2010.
16. NexMed’s company information,
www.nexmed.com/nexact.html, accessed 12/03/2010.
17. Hu L, Damaj BB, Martin R, Michniak-Kohn BB. Enhanced
in vitro transbuccal delivery of ondansetron HCl. Int J Pharm. Epub,
2010 November 5, doi:10.1016/j.ijpharm.2010.10.052.
18. Diani AR, Shull KL, Zaya MJ, Brunden MN. The penetration
enhancer SEPA augments stimulation of scalp hair growth by
topical minoxidil in the balding stumptail macaque. Skin
Pharmacol. 1995, 8(5):221-228.
19. Ekman EF, Strepnik N, Lawson, Schupp JP. Efficacy and
safety of ketoprofen 10% cream in the treatment of pain associated
with acute soft tissue injuries (Phase 3 Study TDLP-110-001). 13th
TransDermal • MARCH 2011
World Congress on Pain, Montreal, Canada, Aug. 29-Sept. 2, 2010,
Poster # PH 420.
20. Voltaren gel information, www.drugs.com/pro/voltarengel.html,
accessed 12/03/2010.
21. Pennsaid information, www.progressive-medical.com,
accessed 12/04/2010.
22. Pennsaid information,
www.medisave.ca/DrugMoreInfo2391.aspx, accessed 12/04/2010.
23. Esba Laboratories’ information,
www.esbalabs.com/medical_information.htm, accessed
12/04/2010.
24. Colloidal lipid dispersion system, www.alpharx.com,
accessed 12/03/2010.
25. Information on Sulidin nimesulide LPS non-steroidal topical
anti-inflammatory gel at http://pharmalicensing.com/public/
outlicensing/view/1160/+, accessed 01/19/2011.
26. Shah K. Mucoadhesive compositions for administration
of biologically active agents to animal tissue. U.S. Patent 5,942,243
(24 August 1999).
27. Shah K, PharmaDur Bioadhesive Delivery System. In
Skin Delivery Systems; Transdermals, Dermatologicals, and
Cosmetic Actives. John J Wille, (ed). Ames, Iowa: Blackwell
Publishing, 2006, pp 211-222.
28. Michniak B, Thakur R, and Shah K. Evaluation of novel
polymer for transdermal permeation of caffeine in presence of different
concentrations of chemical enhancer. Poster # 323,
Proceedings of Controlled Release Society 32nd Annual Meeting,
Miami Beach, Florida, June 2005.
Dr Bozena Michniak-Kohn is a professor in pharmaceutics at the Ernest
Mario School of Pharmacy, Rutgers-The State University of New Jersey in
Piscataway, New Jersey, USA and is the director of the Center for Dermal
Research and Laboratory for Drug Delivery of the New Jersey Center for
Biomaterials (NJCBM). Her research focuses on topical, buccal, and transdermal
drug delivery. Michniak-Kohn has directed over 26 PhD students,
6 Master’s students, and 200+ undergraduates, and the work resulted in
over 350 abstracts, two books, and more than 100 papers and book chapters.
She is a Fellow of AAPS and is a reviewer for over a dozen pharmaceutical
and drug delivery journals.
Dr Kishore R Shah is president of Polytherapeutics, a research and development
company focused on topical mucosal and transdermal drug delivery.
He received his doctoral degree in organic chemistry from the
University of Maryland in College Park, Maryland, USA. He has over 25
years of research experience in the medical device and pharmaceutical
industry, including at Bristol-Myers Squibb and Johnson & Johnson. His
technical expertise includes development of polymeric biomaterials, their
applications, and controlled drug delivery technologies. Shah possesses
experience in taking products from concept to commercialization. He is an
author or co-author of more than 45 patents and technical publications,
several of which are in the field of transdermal drug delivery.
Contact Dr Shah at Polytherapeutics, Inc, 568 Cabot Hill Road,
Bridgewater, New Jersey 08807, USA; Tel: +1 908 393 9938; E-mail:
krshah@polytherapeutics.com.
www.transdermalmag.com
11

12
MARCH 2011 • TransDermal
On the Transdermal Formulation of Peptide
and Protein Drugs
Xiaorong Shen and David Jones, Primera Analytical Solutions
This short review covers some of the recent
approaches to transdermal formulations for
delivering proteins and peptides. These methods
may overcome some of the difficulties
associated with the delivery of those molecules.
Protein and peptide drugs offer powerful therapeutic
benefits to patients. While companies
have marketed them since the introduction
of insulin in the early twentieth century, the methods
for dosing patients usually have been limited
to administration by injection. This method not only
is inconvenient for patients but also causes other
difficulties, such as allergic reactions at the injection
site. For drugs with relatively short half lives, injection
methods — without the use of IV solutions —
do not afford maintenance of appropriate levels of
the drug without repeated dosing. The most convenient
type of dosing, oral, is generally not available
for peptide and protein drugs because proteolytic
enzymes in the alimentary canal hydrolyze the
peptides.
Peptides are widely used in skin-care products,
mostly in connection with the cosmetics industry,
although medical providers routinely apply antibiotic
peptides, such as polymyxin B, topically for
wound care and other dermatological infections.
While such topical use is important, the ability to
transport peptides and proteins into physiological
matrices in other organs is of vital importance.
Proteins incorporate four levels of structure:
• A primary structure that derives from the aminoacid
sequence
• A secondary structure that arrangements in
helices and sheets define
• A tertiary structure that refers to the way that the
secondary structures fit together as a whole
• A quaternary structure that is a representation of
protein-to-protein interactions; for instance, whether
the proteins are monomers, dimers, or oligomers of
single or multiple protein units.
Effects of Structure
All of these structures affect not only the transport of
these molecules but also their activity. To a lesser
extent, the problems with hydrolysis, absorption,
and stability also apply to peptides that, while
smaller, exhibit at least a primary and a secondary
structure. Both proteins and peptides also often
depend on intramolecular bonds that can rearrange
under some circumstances. Most often disulfide
linkages connect these bonds, but some peptides
are cyclic in nature. Again polymixin B is an example.
Any chemical exposure can affect molecular
rearrangement, racemization, and rearrangement of
disulfide bonds, further complicating attempts to
formulate and deliver them.
Nevertheless many approaches to transdermal
formulation are now under active investigation,
and some have reached the stage of clinical
development.
Approaches to Transdermal
Formulation
The dermis is the vascularized portion of the skin
where hair follicles originate, where lymph vessels
and sweat glands are found, and where drugs can

find their way into circulation in other tissues. To
reach the dermis, molecules — in this case large,
sensitive molecules — must penetrate the epidermis,
which generally is about a tenth of a millimeter
in thickness but nonetheless seals off the dermis [1].
Formulators have attempted to transport peptides
across membranes other than those represented by
the skin, such as recent efforts to formulate insulin
as an inhalable product. These efforts have proved
promising and have resulted in the investment of
much effort and money.
Iontophoresis
One transdermal approach that holds significant
promise for accomplishing the task is iontophoresis,
in which a small electrical potential is applied
across skin layers. Proteins and peptides often
exhibit well-defined polarities, deriving from the
location of acidic residues, such as glutamic acid
and aspartic acid, and of basic residues, such as histidine,
lysine, or arginine. Depending on the pH,
these residues can be charged and will migrate
across many matrices. Many laboratory procedures,
such as SDS PAGE, use electrical potentials to separate
and transport peptides and proteins, and iontophoresis
is not all that different except that the
matrix is the skin.
A typical system might consist of two electrodes,
placed in nearby areas of the skin, with a small
potential applied to each. The charged ions are
drawn into the skin
The use of a silver electrode and a silver chloride
electrode is one method that has generated much
interest for the delivery of peptides and proteins
transdermally. A peptide that has a suitable charge,
such as one having a number of arginines, moves in
the direction of the current flow and into the dermis.
After absorption into the tissues, the current maintains
the flow of other ions, such as peptide counterions
or physiological ions such as chloride.
Leutinizing Hormone Releasing Hormone (LHRH)
is a peptide that has been administered successfully
in various settings in this way. This peptide contains
three basic residues — histidine, arginine, and
lysine — and thus is charged [2]. Often researchers
must control the rate of migration carefully; for
TransDermal • MARCH 2011
example, by varying the voltage or the wave form
of the voltage. They can adjust the currents to render
the pro cess essentially painless. Other peptides
delivered transdermally using iontophoresis in -
clude salmon calcintonin [3] and human parathyroid
hormone [4].
Iontophoresis is just one approach and is clearly
only workable with peptides and proteins that are
highly charged and contain either basic or acidic
residues.
Chaperon Molecules
Another approach involves the use of chaperon
molecules to transport proteins across skin layers.
Peptides do affect skin pores, and under the right
conditions, can themselves be used as chaperones
that help transport other peptides across the stratum
corneum. For instance, researchers originally investigated
the peptide Magainin, which is isolated from
frog skin, in clinical trials as a potential anti-infective.
Although regulators ultimately did not
approve the drug for this application, Magainin is
considered a safe compound and is known to
increase pore size and porosity in skin. It works by
disrupting the bilayer structure of the stratum
corneum lipids, increasing porosity [5].
Researchers are investigating insulin delivery in this
way, and many ways to optimize chaperone-type
delivery exist. Samir Mitragotri and his coworkers
in the Chemical Engineering Department at the University
of California Santa Barbara used a combinatorial,
high-throughput-screening process to explore
the transdermal applications of delivering peptides.
Again, the peptide was LHRH [6]. The screening
involved the use of 34 penetration-enhancing
agents, with variable concentrations, allowing for
the screening of thousands of formulations.
Mitragotri was able to show a 100-fold increase in
LHRH delivered to hairless rats and an 80-fold
increase in delivery of macrosugar inulin through
use of the best chaperone formulations that they
developed.
Another approach to maximizing the effectiveness
of small peptides as transdermal chaperone molecules
involves the discovery, via phage display, of
peptides that can penetrate the skin. Wen and his
13

14
MARCH 2011 • TransDermal
coworkers applied a phage library to rat skin and
then collected phages that were isolated from the
animal’s blood stream [7]. They were able to isolate a
peptide with the sequence CSSSPSKHC. The re -
searchers synthesized a cyclized analogue of this
peptide and ultimately were able to show improved
insulin delivery.
Conclusion
The methods described in this article have shown that
it is possible to deliver peptides in vivo via transdermal
routes. This article, however, is not a comprehensive
discussion of such formulations. Many other
transdermal approaches are known, including techniques
such as painless microneedles [8].
References
1. Michniak, et al. European Journal of Pharmaceutics and
Biopharmaceutics. 2005, 60:179–191.
2. Raiman J, Koljonen M, Huikko K, Kostiainen R, Hirvonen
J. Delivery and stability of LHRH and Nafarelin in human skin: The
effect of constant/pulsed iontophoresis. Eur. J. Pharm. Sci. 2004,
21:371–377.
3. Chang SL, Hofmann GA, Zhang L, Deftos LJ, Banga AK.
Stability of a transdermal salmon calcitonin formulation. Drug
Deliv. 2003, 10:41–45.
4. Medi BM and Singh J. Electronically facilitated transdermal
delivery of human parathyroid hormone (1-34). Int. J. Pharm.
2003, 263:25–33.
5. Prausnitz, MR and Langer R. Nature Biotechnology. 2008,
26(11):1261-1268.
6. Karande P, Jain A, Mitragotri S. Nature Biotechnology
2004, 22(2):192-197.
7. Chen Y, Shen Y, Guo X, Zhang C, Yang W, Ma M, Liu S,
Zhang M, Wen L. Transdermal protein delivery by a co-administered
peptide identified via phage display. Nature Biotechnology.
2006, 24(4):455-460.
8. Daniel P. Wermeling et al. Proc Natl Acad Sci. USA 102,
4688–4693 (2005).
Xiaorong Shen received her bachelor’s and master’s degrees in biology at
Nanjing University in China and a PhD in genetics at Purdue
University in the USA. Before receiving her PhD, she worked for more
than eight years at the Chinese Jiangsu Institute on preformulations,
formulations, manufacturing processes, analytical methods, and development.
In 2007, she joined Primera Analytical Solutions where she
now heads its formulations group. She works primarily on advanced
material formulations, including bioresorbable polymers, large-molecule
formulations, and stability and compatibility issues with novel, cuttingedge
formulations.
David Jones joined Primera Analytical Solutions in 2007 and currently
is vice president of sales and marketing. With 25 years in the pharmaceutical
industry, he previously was director of pharmaceutical sales for
Isochem and vice president of development at Hopewell Laboratories. In
the past, he worked on the development of a novel class of peptide
reagents, urethane protected N-carboxyanhydrides (UNCAs), for
Professor Murray Goodman’s laboratories and managed a laboratory at
Multiple Peptide Systems that produced the first commercial peptide
libraries. He received his bachelor’s and master’s degrees in chemistry at
the State University of New York at Stony Brook
Contact David Jones at Primera Analytical Solutions, 259 Wall Street,
Princeton NJ 08534; Tel: +1 908 295 9011; E-mail: david.jones
@primera-corp.com. www.primera-corp.com
www.transdermalmag.com

ISSUE
FOCUS
pharmadur ®
Polytherapeutics has developed
patented transdermal technology
based on its proprietary PharmaDur
polymer. Drug formulation
in the PharmaDur vehicle, as
a gel or emulsion, forms an invisible
and imperceptible hydrogel
film that provides sustained drug
delivery through the skin for 24
hours.
The company’s lead product is
Pharmagesic Transdermal System,
comprising the NSAID diclo -
fenac in PharmaDur gel. Studies
have demonstrated the product to
be capable of producing effective
diclofenac concentrations in the
blood for eliciting systemic pharmacological
activity with once-aday
dosing. The key benefits of
Pharmagesic include sustained
therapeutic activity, minimization
of GI-tract irritation, and potentially
lower systemic-toxicity risks
ContraCt researCh
and development
Located in Princeton, New Jersey,
Primera Analytical Solutions is a
contract research organization
(CRO) founded in 2002. As a CRO,
Primera supports the research and
development of new drug substances.
Primera is FDA-registered
and audited, with no 483s issued.
The company provides a full range
of GLP bioanalytical LC/MS/MS
and immunochemistry services as
well as cGMP analytical services
for drug development — discov-
Formulation
Techniques
by avoiding high, peak diclofe -
nac blood concentrations and
hepatic first-pass metabolism.
Phar magesic and PharmaDur are
available as licensing or partnering
opportunities for use with
other drugs.
ery and preclinical and clinical
programs — and pharmaceutical
product and process development
for small and large molecules. Its
core cap abilities include method
development, validation, sample
analysis, formulation, stability and
release testing, and pharmaceutical
testing services.
Primera Analytical Solutions
Corp
Princeton, New Jersey, USA
Tel: +1 609 921 7715
TransDermal • marCh 2011
Polytherapeutics, Inc.
Bridgewater, New Jersey, USA
Tel: +1 908 393 9938
E-mail:
info@polytherapeutics.com
www.polytherapeutics.com
Fax: +1 609 921 7716
E-mail:
David.Jones@primera-corp.com
www.primera-corp. com
15

16
MARCH 2011 • TransDermal
Calendar
March 2011
12th Skin Forum Annual Meeting.
March 28th and 29th at Campus
Westend, Goethe Universität
in Frankfurt, Germany. Organized
by the International Association
for Pharmaceutical Technology
in partnership with Skin
Forum. www.apv-mainz.de/
index.php?id=277
April 2011
Drug Delivery and Formulation
America 2011. April 27th and
28th at the Hyatt Regency La
Jolla in San Diego, California,
USA. Organized by World Trade
Group (WTG). www.ddfsum
mit.com
July 2011
The 38th Annual Meeting and
Exposition of the Controlled Re -
lease Society. July 30 to August 3
at the Gaylord National Resort
and Convention Center, National
Harbor, Maryland, USA; Tel: +1
651 454 7250 (Minnesota, USA).
www.controlledrelease.org/
main/meetings/default.cfm
August 2011
Barrier Function of Mammalian
Skin. August 7 to 12 at the Waterville
Valley Resort, Waterville
Valley, New Hampshire, USA; Email:
gmenon@ispcorp.com
(New Jersey, USA) or juergen.l
ademann@charite.de (Germany).
www.grc.org/programs.aspx?
year =2011&program=barrier
For less than 2 minutes of your
time, you can receive 6 free issues
of TRANSDERMAL in 2011
anywhere in the world.
www.transdermalmag.com
October 2011
AAPS Annual Meeting and
Convention. October 23 to 27 at
the Washington Convention Center,
Washington, DC, USA; Tel: +1
703 243 2800 (Virginia, USA).
www.aapspharmaceutica.com/
meetings/annualmeet/am11/
exhibit.asp
November 2011
The 1st Annual Symposium of
Drug Delivery Systems. November
3 to 5 in Shenzhen, China.
Organized by Dalian BIT Life Sciences,
Inc, 26 Gaoneng Street,
R401, Dalian Hightech Zone
Dalian, LN 116025, China; Tel:
+0086 411 84799609 821; e-mail:
grace@bitlifesciences.com.
www.bitlifesciences.com/sdds20
11/default.asp
Do you qualify? It’s easy!
Just visit our web site at www.transdermalmag.com
Fill out the form completely.
Make sure all information is correct.
Click on the submit button, and you’re done!
www.transdermalmag.com

January 2012
Drug Delivery Partnerships
2012. January 25 to 27 at Caesers
Palace in Las Vegas, Nevada,
USA. Tel: 1 888 670 8200 (toll free);
+1 941 951 7885 (International); Email:
register@iirusa.com. www
.iirusa.com/ddp/welcome.xml
People news
Corium International
adds two board
members
Menlo Park, California, USA —
Corium International appointed
Dr Bhaskar Chaudhuri and
David L Greenwood to the board
of direc tors. Chaudhuri most
recently served as president of
Valeant Phar maceuticals International
and previously was president
and CEO of Dow Pharmaceutical
Services. Greenwood is
executive vice president and CEO
of Geron Corporation.
Aveva hires alliance
management director
and marketing
manager
Miramar, Florida, USA — Aveva
Drug Delivery Systems hired Paul
Davis as director, alliance management,
and Jared Hahn as marketing
manager, both reporting
directly to Robert J Bloder, vice
president. With over eight years of
experience at Beckman Coulter,
Davis spent the last four years in
business development and
alliance management. Jared Hahn
most recently worked for over
eight years at Technology Catalysts
Inter national (TCI), managing the
company’s pharmaceutical and
drug-delivery services, including
the marketing of TCI’s services to
pharmaceutical companies.
Avantor names new
CEO
Phillipsburg, New Jersey, USA
— Avantor Performance Materials
named Jean-Marc Gilson as
chief executive officer. Gilson was
previously executive vice president
and general manager of
Dow Corning’s specialty chemicals
business.
Alliqua appoints five
directors to board
New York, New York, USA —
Alliqua, previously Hepalife
Technologies, appointed five
mem bers to its board of directors.
Joseph M Leone is an expert in
commercial lending to small and
midsized businesses. Michael
Goldberg, MD, currently is a
managing partner at the investment
firm Montaur Capital Partners.
Nochum Stein currently
serves as Chairman and CEO of
American European Group
(AEG), a New-York-based in surance
holding company focusing
on supporting small to mid-sized
businesses. Kenneth Pearsen,
MD currently is the CEO of Western
New York Radiology Associates.
Jeffrey Sklar is the managing
partner of Sklar, Heyman,
and Company, a re gional accounting
firm.
Alliqua retains
strategic consultant
New York, New York, USA —
Alli qua, previously Hepalife
Tech nologies, appointed Dr
Ronald S Harland as a strategic
consultant. Harland has worked
in the field of product development
and studied advanced drug
delivery systems and applications
for over 20 years. Previously,
Harland was founder and
CEO at PharmSolv.
Supplier news
Adhesives Research
receives ISO 13485
certification
Glen Rock, Pennsylvania, USA
— Adhesives Research received
ISO 13485 certification for its North
American manufactur ing facility
in Glen Rock. This certification
supplements the company’s existing
ISO 9001 standards.
NuSil introduces
thermally conductive
silicones
Carpinteria, California, USA —
NuSil Technology introduced two
thermally conductive, health care
silicone elastomers that can be
used as a cure-in-place adhesive
or potting compound between
electrical components and heat
sinks to keep medical devices
operating at optimal levels. With
a two-part configuration, MED-
2980, a 1.6 W/(mK) silicone, is
good for larger devices. With low
volatility and low ionic con tent,
MED-2955 serves more sensitive
electronic devices or processes.
IDEX acquires Microfluidics
International
Lake Forest, Illinois and Newton,
Massachusetts, USA —
IDEX will acquire Microfluidics
International for $1.35 per share,
net to the seller in cash and subject
to adjustment as defined in
the merger agreement. The companies
expect the transaction to
close in the first quarter of 2011.
Advertiser index
Aveva Drug Delivery
Systems •••••••••••••••• Cover 4
TapeMark•••••••••••••••••••••••3

T R A N S D E R M A L T R A N S C E N D E N C E
A h i g h e r l e v e l o f p e r f o r m a n c e D e l i v e r s n e w p o s s i b i l i t i e s
That’s the promise of Aveva Drug Delivery Systems,
combining innovation and unparalleled industry
experience to advance drug delivery and pioneer
new frontiers in transdermal drug delivery for new
chemical entities and life cycle management
opportunities to enhance existing products.
As one of the world’s largest manufacturers
of transdermal patches offering a full range
of research, development and manufacturing
capabilities, Aveva transcends traditional limitations
of patch technology and business partnerships to
achieve new levels of product and corporate
performance.
© Copyright 2005. Aveva Drug Delivery Systems. All rights reserved.
> Customizing solutions to the unique characteristics
of each drug
> Masterfully balancing the patch properties of
adhesion reliability and gentleness that lead to
an enhanced patient experience.
> Managing a higher drug concentration in a
smaller patch
A flexible, customer-oriented business philosophy
that adds value to projects and exceeds customer
expectations.
To license a product or to see how we can add value
to your project, call Robert J. Bloder, Vice President
Business Development, at 954.624.1374 or visit
www.AvevaDDS.com