Posts Tagged ‘TDD system’

Author, Editor: Tilda Barliya PhD

Transdermal drug delivery is a very exciting and challenging research area. It is defined 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 difficult 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 first understand the skin anatomy and it’s implication of drug-of choice and method of delivery.

The Anatomy of the skin

Human skin comprises of three distinct but mutually dependent tissues :

  •  The stratified, 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 flexible 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 difference 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) offers many advantages over conventional delivery systems yet has several limitations (3).


  • avoidance of hepatic first 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


  • Possibility of local irritation at the site of application (Erythema, itching, and local edema as well as severe allergic reaction).
  • Skin’s 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 benefit. Drugs with a lipophillic character, however, are better 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 significant resistance to permeation. This is because the drugs must cross the lipophilic membrane of each cell, then the 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 μm, the actual diffusional path of most molecules crossing the skin is on the order of 400 μm. 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 little 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 efficiency.

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) :

  1.  Matrix or Monolithic: The inert polymer matrix binds with the drug and controls it’s release from the device.
  2. 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.

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
  • Diffusion coefficient
  • Partition coefficient

To date, there are several approved TDD patches on the market (3) (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995530/table/T2/) and several other ongoing clinical Trials:clinical trials see link  (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995530/table/T3/)

As this topic is very complicated and requires a careful evaluation of the different products on the market, we’ll go dig deeper into the different TDD systems and analyze several examples, in the following post.


1. Nilkhil Sharma., Geta Agrawal.,  A. C. Rana., Zulfiqar 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.

Click to access File%20no%206%20Vol%203%20Issue%203.pdf

2. Yakov Frum – Bradford School of Pharmacy


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. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995530/

5. http://www.manufacturingchemist.com/technical/article_page/Liftoff_for_needlefree_delivery/39384.

6. http://www.ncbi.nlm.nih.gov/pubmed/21413905

7. Greg Russell Jones: http://www.mentorconsulting.net/News.htm

see detailed papers on this link no.7  with active PDF files.

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