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Introduction to Transdermal Drug Delivery (TDD) system
and nanotechnology
January 28, 2013 by tildabarliya






i
5 Votes
Author, Editor: Tilda Barliya PhD
Transdermal drug delivery is a very exciting and challenging research area. It is dened as the
administration of therapeutic drugs through the skin. The human skin is a readily accessible surface for
drug delivery (1). Skin of an average adult body covers a surface of approximately 2 m2 and receives
about one-third of the blood circulating through the body. Over the past decades, developing controlled
drug delivery has become increasingly important in the pharmaceutical industry.
The potential of using the intact skin as the port of drug administration to the human body has been
recognized for several decades, however the skin is a very dicult barrier to the ingress of materials
allowing only small quantities of a drug to penetrate over a period of time. In order to design a drug
delivery system, one must rst understand the skin anatomy and its implication of drug-of choice and
method of delivery.
The Anatomy of the skin
Human skin comprises of three distinct but mutually dependent tissues :
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The stratied, vascular, cellular epidermis (stratum corneum and viable
epidermis),
Underlying dermis of connective tissues
Hypodermis
The Epidermis: This is the outermost layer of skin also called as horney
layer. It is approximately 10mm thick when dry but swells to several
times this thickness when fully hydrated. It contains 10 to 25 layers of
dead, keratinized cells called corneocytes. It is exible but relatively
impermeable. The stratum corneum is the principal barrier for
penetration of drug.
The Dermis : Dermis is 3 to 5mm thick layer and is composed of a matrix of connective tissue, which
contains blood vessels, lymph vessels and nerves. Capillaries reach to within 0.2 mm of skin surface and
provide sink conditions for most molecules penetrating the skin barrier. The blood supply thus keeps the
dermal concentration of a permeant very low and the resulting concentration dierence across the
epidermis provides the essential concentration gradient for transdermal permeation.
The Hypodermis: The hypodermis or subcutaneous fat tissue supports the dermis and epidermis. It serves
as a fat storage area. The cutaneous blood supply has essential function in regulation of body
temperature.
For transdermal drug delivery, drug has to penetrate through all these three layers and reach
into systemic circulation while in case of topical drug delivery only penetration through stratum
corneum is essential and then retention of drug in skin layers is desired.
Transdermal drug delivery (TDD) oers many advantages over conventional delivery systems yet has
several limitations (3).
Advantages:
avoidance of hepatic rst pass metabolism,
The steady permeation of drug across the skin allows for more consistent serum drug levels
non-invasive nature of drug application
convenience
improved patient compliance and discontinuation of administration by removal of the system
Disadvantages:
Possibility of local irritation at the site of application (Erythema, itching, and local edema as well as
severe allergic reaction).
Skins low permeability limits the number of drugs that can be delivered in this manner (Many drugs
with a hydrophilic structure permeate the skin too slowly to be of therapeutic benet. Drugs with a
lipophillic character, however, are beer suited for transdermal delivery).
Two main routes of Traditional Transdermal Drug Penetration (3):
Transcellular pathway Drugs cross the skin by directly passing through both the phospholipid
membranes and the cytoplasm of the dead keratinocytes that constitute the stratum
corneum. Although this is the path of shortest distance, the drugs encounter signicant resistance to
permeation. This is because the drugs must cross the lipophilic membrane of each cell, then the
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hydrophilic cellular contents containing keratin, and then the phospholipid bilayer of the cell one more
time. This series of steps is repeated numerous times to traverse the full thickness of the stratum
corneum. Few drugs have the properties to cross via this method.
Intercellular (Paracellular) route - Drugs crossing the skin by this route must pass through the small
spaces between the cells of the skin, making the route more tortuous. Although the thickness of the
stratum corneum is only about 20 m, the actual diusional path of most molecules crossing the skin is
on the order of 400 m. The 20-fold increase in the actual path of permeating molecules greatly
reduces the rate of drug penetration.
A less important pathway of drug penetration is the follicular route. Hair follicles penetrate through
the stratum corneum, allowing more direct access to the dermal microcirculation. However, hair
follicles occupy only 1/1,000 of the entire skin surface area. Consequently, very lile drug actually
crosses the skin via the follicular route.
For thransdermal delivery , the skin condition (pH and temp, age, blood supply, hydration etc) is of major
impact on the eciency.
The basic components of any transdermal delivery system include the drug dissolved or dispersed in
an inert polymer matrix that provides support and platform for drug release. There are two basic designs
of the patch system that dictate drug release characteristics and patch behavior (1) :
Matrix or Monolithic: The inert polymer matrix binds with the drug and controls its release from the
device.
1.
Reservoir or Membrane: The polymer matrix does not control drug release. Instead, a
rate-controlling membrane present between the drug matrix and the adhesive layer provides the
rate-limiting barrier for drug release from the device.
2.
(hp://www.iontera.com/wp-content/uploads/2012/06/IonIQ-cross-
section.jpeg)
Example of a TDD system is a systems in which, the drug reservoir
is sandwiched between a drug-impermeable backing laminate and a rate
controlling polymeric membrane.
Along the biological aspect of the skin condition (pH and temp, hydration
etc) the chemical composition of the drug of choice and polyer martix are
also of crucial nature.
Drug type (lipid, protein, macromolecule etc)/ Molecular size and shape
Drug concentration
Diusion coecient
Partition coecient
To date, there are several approved TDD patches on the market (3) (hp://www.ncbi.nlm.nih.gov
/pmc/articles/PMC2995530/table/T2/ (hp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995530/table/T2/))
and several other ongoing clinical Trials:clinical trials see link (hp://www.ncbi.nlm.nih.gov/pmc/articles
/PMC2995530/table/T3/ (hp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995530/table/T3/))
As this topic is very complicated and requires a careful evaluation of the dierent products on the
market, well go dig deeper into the dierent TDD systems and analyze several examples, in the following
post.
Introduction to Transdermal Drug Delivery (TDD) system and nanotechno... http://pharmaceuticalintelligence.com/2013/01/28/introduction-to-transd...
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on January 28, 2013 at 8:28 PM | Reply
Ref:
1. Nilkhil Sharma., Geta Agrawal., A. C. Rana., Zulqar Ali Bahat., and Dinesh Kumar. A Review:
Transdermal Drug Delivery System: A Tool For Novel Drug Delivery System. Int. J. Drug Dev. & Res.,
Jul-Sep 2011, 3 (3): 70-84.
hp://ijddr.in/old/Dacuments/1/File%20no%206%20Vol%203%20Issue%203.pdf (hp://ijddr.in
/old/Dacuments/1/File%20no%206%20Vol%203%20Issue%203.pdf)
2. Yakov Frum Bradford School of Pharmacy
hp://www.gla.ac.uk/services/postgraduateresearch/scholarships/macrobertson
/macrobertsonscholarshipreports/2005-6awards/yakovfrum-bradfordschoolofpharmacy/
(hp://www.gla.ac.uk/services/postgraduateresearch/scholarships/macrobertson
/macrobertsonscholarshipreports/2005-6awards/yakovfrum-bradfordschoolofpharmacy/)
3. Eseldin Keleb, Rakesh Kumar Sharma2, Esmaeil B Mosa, Abd-alkadar Z Aljahwi. Transdermal Drug
Delivery System- Design and Evaluation. International Journal of Advances in Pharmaceutical Sciences 1
(2010) 201-211.
4. hp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995530/
5. hp://www.manufacturingchemist.com/technical/article_page/Lifto_for_needlefree_delivery/39384.
6. hp://www.ncbi.nlm.nih.gov/pubmed/21413905
7. Greg Russell Jones: hp://www.mentorconsulting.net/News.htm
see detailed papers on this link no.7 with active PDF les.
Posted in Bio Instrumentation in Experimental Life Sciences Research, BioSimilars, CANCER BIOLOGY
& Innovations in Cancer Therapy, Disease Biology, Small Molecules in Development of Therapeutic
Drugs, Drug Delivery Platform Technology, Nanotechnology for Drug Delivery, Pharmaceutical R&D
Investment | Tagged Intercellular (Paracellular) route, skin, TDD system, Transcellular pathway,
Transdermal Drug Delivery System | 5 Comments
5 Responses
larryhbern
Right on.
I just found this, very much consistent with your thesis.
Rethink Transdermal
Anne M. Roush, Business Development Director, Transdermal and Inhalation Technologies, 3M Drug
Delivery Systems
In the face of a signicant patent cli, many companies in the pharmaceutical industry are seeking
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on January 29, 2013 at 6:14 AM | Reply
on January 29, 2013 at 6:22 AM | Reply
on January 29, 2013 at 4:58 PM | Reply
new ways to protect their brands as long as possible, and reformulation presents one of the most
obvious ways to do this. Historically, these endeavors were undertaken on a reactionary basis, for
example, when a drug product has enjoyed a successful run but is facing new competitive threats from
generics. Contemporary product life-cycle management is more strategic, and employs a proactive
approach to reformulation earlier in the product development cycle. In other cases, reformulation can
be undertaken for product dierentiation as a means to give patients and their caregivers more
options, which beer suit their needs.
Transdermal delivery oers a number of competitive advantages for pharmaceutical companies. For
many, the oral route is the default delivery method when creating a new pharmaceutical product.
Unfortunately, in hewing to this mindset, many companies are missing out on the valuable
opportunity presented by transdermal delivery. By starting life-cycle management earlier and including
transdermal as a parallel path during development, a pharmaceutical company is beer positioned to
strategically introduce various formulations to boost the original products brand and consumer
preference.
Transdermal is not only underutilized for life-cycle management purposes, but also in initial screening
of compounds. We have seen that it is not uncommon for a pharmaceutical company to reject
candidate molecules after screenings show they are not a good t for oral delivery when, in fact, these
molecules could be a very good t for transdermal delivery. By including transdermal delivery in the
initial consideration, companies open up the number of viable candidates to pursue.
Transdermal delivery has the potential to oer improved safety (e.g, gastrointestinal related side
eects), and ecacy by avoiding rst pass metabolism and maintaining more constant drug levels
(versus the peak and trough eect seen with oral delivery), as well as increased compliance through
sustained release for up to 7 days. These benets can ultimately translate to a dosage form that is more
patient and caregiver friendly.
2012pharmaceutical
Great post, enjoyed reading it very much.
In next posts, please
A. Provide a classication of TDD, along your own plan, I.e.
By Indication:
1. smoking cessation assists nicotin patch
1.2. Pain management
1.2.1. Dilaudid, controlled distance
1.2.2. LIdoderm, capsicum,
2. Psychotropic drugs
3. Nitroglicerin
4. Antibiotics
B. Elaborate activity in the clinical trials space
2012pharmaceutical
Dr. Larry,
Great comment, we are on the sme page, here.
Gregory Russell-Jones
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on January 31, 2013 at 12:05 AM | Reply
I am sure that Tilda will deal with this later, but there is the obvious advantage of local
application of drugs, particularly for the many skin complaints that keep dermatologists in
business, particularly psoriasis, ezcema, etc. There is also a potential to avoid the highly
proteolytic environment that oral delivery presents. In addition good trandermal delivery systems aim
to avoid the pain and discomfort that occurs with traditional injectables
Arun Kedia
VAV Life Sciences oers puried Soya Phospholipids, the ideal membrane friendly carrier of
drugs across the skin. We are happy to oer free samples to researchers.
Arun Kedia
arun@vav.in
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