qps on Transdermal Delivery Systems

Introduction
human-skin

Whereas dermatologic topical formulations (foams, creams, lotions, ointments, gels, etc.) target skin diseases, topical transdermal delivery systems (TDDS) are designed to treat systemic medical conditions or localized joint or muscle conditions, using the skin as the route of drug delivery. Transdermal drug delivery offers important advantages over other routes of administration. It is particularly useful for circumventing liver first-pass metabolism, as an alternative to oral products, for non-invasive localized muscle and joint treatments, to improve and simplify patient compliance, and to allow for discontinuation of drug delivery by removing the patch in the event of adverse drug reactions. TDDS have become successful alternatives for delivering medications to young children, the elderly and the infirm.

From the first transdermal patch - for motion sickness (Scopolamine; Transderm Scop®; Novartis Consumer Health, Inc.) - approved by the FDA in 1979, to the most recently approved patch, for chronic pain (Buprenorphine; Butrans®; Purdue Pharma L.P.), a total of 22 transdermal systems have been commercialized as prescription products so far. Several over-the-counter (OTC) products are also available, including patches containing nicotine, oxybutynin, capsaicin, and menthol, to name a few.

The transdermal delivery system industry is growing, worldwide. Representing more than 12% of the global drug delivery trade, this market was valued at $21.5 billion in 2010 and is expected to reach $31.5 billion by 2015. The annual U.S. transdermal patch market was estimated at more than $3 billion in 2010, with flagship contraceptive, hormone replacement, and pain relief products accounting for more than half of total sales. Pharmaceutical, biotechnology, and drug delivery companies
continue to evaluate new applications for transdermal drug delivery including treatments for migraine, HIV, osteoporosis, stroke and restless leg syndrome. The future development of successful transdermal drug delivery systems in a widening array of therapeutic areas will play an important role in improving patients’ quality of life by providing alternatives to conventional oral and injectable drugs.

Beyond the proprietary products, the generic industry is rapidly expanding the market with bioequivalent transdermal systems. The approval process for transdermal generic products has been facilitated by the FDA with recommendations outlining the necessary studies for demonstrating not only bioequivalence (systemic delivery),

but also non-inferiority for adhesion, irritation and sensitization to the reference product [1]. The FDA has also recently issued a guidance related to residual drug content for transdermal systems [2].

Developing new transdermal systems presents challenges in identifying the best body site for application, establishing bioavailability, monitoring efficacy, determining the appropriate duration of application, and quantifying residual drug. Adhesion, irritation and sensitization must also be considered. A well designed and integrated development plan is needed to achieve rapid approval.

Transdermal Drug Delivery Systems

Although transdermal systems are classified variously, transdermal patches can be divided into three main categories according to how the drug is incorporated into the delivery system:

  • An adhesive matrix patch is a system in which the adhesive layer contains the drug. In this type of patch, the adhesive layer not only serves to fix the TDDS to the skin but is also responsible for the controlled release of the drug.
  • A reservoir patch is a system with a liquid compartment containing a drug solution or suspension, enclosed by an adhesive layer and a semi-permeable membrane to control release.
  • A matrix patch is a system which includes a semisolid matrix containing a drug solution or suspension, independent of the adhesive.

Non-patch topical transdermal systems have also become popular. They are typically gels and creams, such as those designed to deliver testosterone, progesterone, and diclofenac sodium.

Apart from traditional transdermal patch products, extensive work is ongoing to develop microporation technologies and devices, most of which are intended to disrupt or bypass the stratum corneum, the rate-limiting barrier of the skin. Microporation techniques currently in development include laser ablation, radiofrequency (iontophoresis, sonophoresis, electroporation), thermal technologies (drug delivery augmented with heat), and microneedle systems. These diverse developing technologies are being investigated for use with a wide variety of difficult-to-deliver drug compounds and macromolecules (e.g. parathyroid hormone, insulin, vaccines, and biologics), and for drugs requiring rapid delivery (e.g. lidocaine, fentanyl and diclofenac).

Several of these systems are already available OTC, including microneedle rollers and iontophoresis and sonophoresis systems, which are predominately being used for cosmetic and anti-aging treatments and as therapy for localized sports injuries.

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