Transdermal drug delivery systems have brought about a change in the way medication is delivered to patients, and are now becoming one of the most popular forms of delivery. Here, Medherant’s Sukhy Nandra, Vasiliki Nikolaou and David Haddleton discuss the benefits and limitations of this technology.
Delivery
The transdermal route
The efficacy of a medicine is highly dependent on drug delivery, the capacity of the drug to reach its target in the patient. Most active pharmaceutical ingredients (APIs) are delivered via the oral or parenteral routes, oral being the most popular. However, many drugs fail to progress as effective delivery is limited or not possible. To overcome this problem, transdermal drug delivery is a rapidly developing area and is becoming increasingly popular. Delivery of the drug through the skin can be used to alleviate local pain, treat a disease via systemic delivery or even detect an illness as wearable diagnostics become more common. These systems can improve therapeutic efficacy and safety as the drug is delivered through the skin at a predetermined and controlled rate. The drug is absorbed via the skin and enters the circulatory system. Among the various types of transdermal delivery, transdermal patches dominate the market and have now become a proven technology to deliver a specific dose of medication directly into the bloodstream.
The skin has been exploited as a drug delivery route for many years, whether this involved using homemade ointments or more recently, transdermal patches. The first product to reach the market was a Scopolamine patch in 1979, used to treat motion sickness. All patches are made up of the following key components; a backing liner, a release liner, the adhesive and, most importantly, the drug itself. Depending on the nature of the drug, different types of patches can be used. The two main types are reservoir patches which utilise a membrane to hold the drug in a reservoir and allow gradual release, and drug-in-adhesive patches which contain the drug dissolved in the adhesive. Polymer selection and design are the most important factors in determining the success of a transdermal patch. The overall performance of the system depends on efficient skin adhesion as a detached patch surface will reduce the amount of drug permeating the skin, compromising the efficacy of the therapy. Nevertheless, some of the currently available transdermal patches utilise adhesive matrices that do not provide sufficient adhesion to all body parts or under specific circumstances (e.g. while bathing), are painful to remove and can leave a residue of adhesive on the skin. The development of novel adhesive matrices therefore requires further scientific research.
Comparing transdermal patches to alternative medications
With transdermal medicated patches, drug release can be controlled by the use of excipients and a rate limiting membrane. This introduces a control over release rate that is not possible with oral drugs. These systems also remove the need to constantly re-administer the drug, which is very useful for people suffering from conditions that inhibit memory or those with busy schedules. In case of an emergency such as a change in condition or an allergic reaction, a drug may need to be removed immediately, something that is easy to do with a transdermal patch.
With oral drugs, digestion can break down the drug before it is released into the system and can exert its effect. There are several drawbacks to this. Firstly, the digestive tract is susceptible to damage over extended periods of use with drugs such as ibuprofen. This can induce stomach ulcers and intestinal lining damage. It is also an issue for people who already take several oral drugs, as gastric reflux issues are a common issue. Secondly, a substantial amount of the drug can be digested, meaning that only a small amount is actually available to carry out its function (bioavailability). Transdermal patches allow the drug to be kept localised at the site of administration or become systemic, depending on the nature of the drug. Patches are also less invasive than intravenous injections, allowing better patient compliance and comfort.
Recent advances
The advent of transdermal drug delivery systems has unlocked a new area of research with large potential and which is progressing quickly. Despite the remarkable advances made so far, there are still hurdles to overcome including biological barriers, elimination of initial burst release and formulation of poorly water-soluble drugs to include more drug classes. One area of innovation has therefore been to improve the adhesive formulations used in patches. Many polymers are routinely employed as the adhesive matrix including polyacrylates, polyurethanes and silicone-based polymers. Among the different adhesive formulations, hot-melt pressure sensitive adhesives (HMPSAs) are of interest due to their low irritation and good adhesion. Moreover, they are solvent-free systems and they can be formulated to contain little or no chemical functionality, reducing the possibility of interactions with the active ingredients. Medherant has developed a user-friendly transdermal technology platform based on a novel pressure sensitive adhesive. This platform enables a high payload of various active ingredients while maintaining good adhesion. We’re currently performing clinical trials of the company's first ibuprofen patch (TEPI) which is estimated to be on the market by 2020.
The invention of transdermal drug delivery systems initiated a revolution in the world of drug delivery, offering several advantages over traditional routes. However, the potential of these systems is not yet fully realised, and more research needs to be done in order to achieve the technological advancements that will lead to enhanced disease prevention, diagnosis, control and improvement in health for patients worldwide.