API characteristics for Transdermal Drug Delivery Systems

Alejandro Scasso – Pharmaceutical Technology Manager


In order for an IFA to be administered through the skin, it must meet certain characteristics.

Viewed from different angles, the administration of drugs through the skin offers incomparable advantages

  • Avoid first-pass hepatic metabolism which allows reducing the intake dose to achieve a therapeutic effect
  • Easy administration compared with injectables, intranasal, and even oral dosage forms when the swallowing process is altered
  • Accurate dosage metering, especially when referring to transdermal patches
  • Easy medication management for patients and caregivers
  • Wide administrations periods, ranked from hours to one a week
  • Non-invasive
  • Controlled drug release particularly useful in painkillers chronic administration and hormone replacement therapies
  • Faster dosage interruption compared to other extended-release medications


In this article, it is solely considered “Passive” transdermal dosage forms, where the drug, freely diffuses through the skin due to a chemical gradient acting as a “driven force”. Other “Active” dosage forms require additional energy to deliver the drug. Make sense to mention within this group, the iontophoretic devices where, an electric current, forces the ionized drug to pass through the skin. Microneedles and electroporation cause a mechanical or thermal alteration of stratum corneum porous to improve the passage of drugs.


In this article, we particularly are focused on patches rather than on gels and cremes. Nevertheless, should be recognized that semisolid dosage forms have been demonstrated to be safe and efficient to deliver hormones, corticoids and anti-inflammatories, becoming key medicines for the treatment of specific diseases.


Although the benefits of transdermal delivery appear to be outstanding for a large number of drugs and therapies, only a small number of transdermal products are available worldwide.


The main reason for the limited existence of drugs administered transdermally is a consequence of the characteristics of the APIs involved, specifically, the size of the molecule and the therapeutic dose. In fact, not all APIs are likely to be administered through the skin to produce a scientifically proven therapeutic effect.


The landscape for “Passive” transdermal administration suddenly drops into small-size molecules, dismissing from the scenario a lot of current, highly efficient therapies, involving medium and big size molecules.


In general terms, it is accepted that an API is feasible to be administered through the transdermal route if meets the following attributes:

  • Molecular weight < 400 D
  • Daily dose < 20 mg/day
  • Melting point < 200 ºC
  • log PO/W: –1.0 and 4.0
  • Slightly water soluble
  • Half-life < 10 h
  • No irritant and no sensitizing


Permeability of a drug is defined as the amount diffusing through one square centimeter of intact skin during a finite period of time. Thus, the dose delivered can be metered by adjusting the area of the skin affected and the involved period of time. Should be considered that there is a rational threshold, limiting, from the wear and comfortability of the patient, the acceptable size of a transdermal patch.

In line with the size, the patches offer and clear advantages over gels and cremes since the area of skin involved is very well defined by the patch size while in semi-solids, the area affected is more difficult to be limited either in single or in repeated dose administration.

The following table summarizes the most relevant characteristics of APIs marketed worldwide from transdermal patches


  • Highest transdermal dose approved/commercialized
  • Bigger patch size available in the market
  • Daily dose based on 9 hours of exposure. Extrapolated to 24 hours could reach 80 mg/day


As can be seen, not all the API successfully commercialized in the transdermal market, meets all theoretical attributes.

Buprenorphine has a molecular weight higher than 400, however, a well-formulated patch can reach the target doses.

Rotigotine exceeds the desirable lipophilicity, however, is a successful product, and nowadays, the only dosage form for rotigotine administration

Methylphenidate represents the patch with the highest daily dose delivered.

Capsaicin is far away the biggest patch and the one with the shorter wearing

Patch size varies from less than 10 sqcm to 280 sqcm centimeters. It is generally accepted that the desired size of a patch is less than 75 sqcm. Larger patches will be less comfortable to wear and more difficult to handle.

As there are no fixed rule and have been seen several exceptions, a short benchwork feasibility study is the making decision tool Amarin offer to identify transdermal drug candidates.

A feasibility study considers the elaboration of simple prototypes. It means combining the API of interest in selected adhesives and evaluating the penetration and stability of the drug to conclude whether the therapeutic doses of the API under consideration can be administered from a reasonably sized patch and also to predict future difficulties and limitations to carry out. a full development program.

There are dozens of relatively new APIs that have proved to be safe and efficient for several therapies and possess physicochemical characteristics to become ideal candidates for transdermal administration.

If you are interested in exploring a particular API for transdermal delivery, please do not hesitate to contact the Amarin team for a discussion of ideas and setting of feasibility activities.


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