Transdermal Drug Delivery Systems
Transdermal drug delivery systems provide an attractive alternative route to deliver medication. From the first system approved in 1979 to now, there are 19 transdermal delivery systems with FDA approval. This field has significantly grown and holds potential for further growth. Currently, the general criteria of a compound for transdermal delivery are low doses, half life less than 10 hours, molecular weight 500 Da, Log Partition coefficient between 1-3, low oral bioavailability, and low therapeutic index. These criteria limit the application of transdermal drug systems to drug development. Another limiting aspect of transdermal drug delivery is the permeability of the skin layers consisting of the stratum corneum and the viable dermis However with increasing research on improving current methods, while developing newer advanced systems such as micro needles, ultrasound, microdermabrasion and chemical enhancers more compounds are able to be applied to transdermal systems. Through the enabling of more compounds to be pursed for transdermal drug delivery, the field can have a substantial impact on patients and drug development.
Research in transdermal drug delivery systems has significantly increased over the past ten years. Currently, the worldwide market for transdermal drugs is approximately four-billion dollars and is increasing each year with advancements in methods, strategies and technologies1. However the challenge of passing the barriers of the stratum corneum and the viable dermis are a significant limitation, reducing the amount of potential drug compounds available for transdermal drug delivery systems. With increasing focus and improvements in enhancing the permeability of these two skin layers, capabilities of these systems increase leading to more drugs being applied to transdermal systems . Overview
In theory, the approach to transdermal drug delivery systems is simple. It consists of applying a drug in high concentrations in a patch and wearing it on the skin over a period of time. With the high concentrations in the patch and a constant low concentration in the blood due to constant circulation, the drug will diffuse across the skin over a significant period of time. The approach seems simple, however in depth these systems are extremely complex and intricate. Before even developing and designing transdermal systems, skin structure and physiology needs be understood as this is what the system is being applied too. The skin is composed of three layers the stratum corneum, the viable epidermis and the dermis. The outer most layer of the skin is called stratum corneum which is a significant barrier to transdermal drug delivery. It is composed of approximately ten to fifteen sheets of corneocytes and is about ten to fifteen micro meters thick2. To simplify the structure has been said to have “brick and mortar” like composition with the corneocytes being the bricks whereas the fatty acids, cholesterol, and triglycerides compose the mortar2. This “brick and mortar” structure limits the diffusion of drug compounds towards the blood capillaries located in the vascular dermis. The middle layer of the skin is the viable epidermis. This layer lies just below the stratum corneum and above the epidermis. The viable epidermis is composed of many diverse cells including Langerhans cells which cascade immune responses as well as keratinocytes, and melanocytes3. Being a non-vascular component of the skin and containing no nerve endings, the viable epidermis and the stratum corneum are ideal targets for painless drug delivery. Lastly, the dermis is the lowest layer of the skin that separates the epidermis from the subcutaneous tissues. Fibroblasts, macrophages and adipocytes are some of the different cell types that compose this layer3. Important parts of the dermis are the matrixes of collagen and elastin,...