Transdermal Application of Drugs

Transdermal is an administration route for drugs wherein active ingredients are transmitted across the skin for systemic distribution. Examples are patches that are used for medical delivery and implants that are used for medical purposes. The skin is a large target for drug delivery and its basic functions limit its utility for this kind of purpose. The functions of skin are mainly to protect the body from external invasion such as harmful substances and microorganisms. Its other function is to contain all fluids in the body. The skin has to be tough and flexible enough to allow for movement. The lipids in the skin will serve as poor conductors of electricity and they can protect us from electrical currents if needed. The two important layers to our skin are the epidermis and the dermis. For transdermal delivery, the drugs have to pass through two sub-layers of the epidermis to reach the microcirculation of the dermis. Stratum corneum is the top layer of the skin and it varies in thickness from ten to several hundred micrometres based on the body region. It is composed of layers of dead and flattened keratinocytes that are surrounded by a lipid matrix that act as a brick and mortar system and it is tough to penetrate. This layer offers a significant barrier to diffusion. It is barrier to almost 90% of all transdermal drug applications. All molecules penetrate this layer to some degree. Below this layer is the epidermis. It is about ten times as thick as the stratum corneum. Diffusion is much faster due to the degree of hydration in the living cells of the epidermis. Below it is the dermis which is one millimeter thick and that is hundred times the thickness of stratum corneum. The dermis contains vessels that distribute drugs into the systemic circulation and regulate temperature to maintain microcirculation. Transdermal Pathways There are two major pathways through which drugs can cross your skin and each the systemic circulation. The direct route is known as the transcellular pathway. With this route, drugs will cross the skin by passing directly through the phospholipids membranes and the cytoplasm of the dead keratinocytes that make up the stratum corneum. Though this is the track of shortest distance, the drugs will experience considerable resistance to permeation. It is because they have to cross the lipophilic membrane of every cell and the hydrophilic cellular contents that contain keratin and then they have to cross the phospholipids bi-layer of the cells again. This chain of steps has to be repeated several times to travel the full thickness of the stratum corneum. Another common pathway through the skin is the intercellular route. Drugs that cross the skin through this route have to pass through the small spaces between the skin cells, making the route a laborious one. The twenty-fold increase in the actual path of permeation of molecules reduces the rate of the penetration of the drugs. A third pathway to breach the stratum corneum is through the small micro-channels that are created by a medical micro-needling device. It comes in many variants and brands. A standard Franz diffusion cell was used at the University of Marburg in Germany to show that this approach is effective in enhancing skin penetration ability for lipophilic and hydrophilic compounds. This micro-needling approach is considered as the vaccine of the future. The devices and formulations for transdermally administered drugs include transdermal patch and transdermal gel.