Transdermal drug administration routes

What is transdermal drug administration What are the theoretical advantages of this route of administration What considerations must be taken into account when using this route ... 

The transdermal route of drug administration offers several advantages over other methods of delivery. For some cases, oral delivery may be contraindicated, or the drug may be poorly absorbed. This would also include situations for which the drug undergoes a substantial first-pass effect [173] and systemic therapy is desired. 

Parenteral administration is not perceived as a problem in the context of drugs which are administered infrequently, or as a once-off dose to a patient. However, in the case of products administered frequently/daily (e.g. insulin to diabetics), non-parenteral delivery routes would be preferred. Such routes would be more convenient, less invasive, less painful and generally would achieve better patient compliance. Alternative potential delivery routes include oral, nasal, transmucosal, transdermal or pulmonary routes. Although such routes have proven possible in the context of many drugs, routine administration of biopharmaceuticals by such means has proven to be technically challenging. Obstacles encountered include their high molecular mass, their susceptibility to enzymatic inactivation and their potential to aggregate. 

Walters KA. Transdermal drug delivery. In Florence AT, Salole EG, eds. Routes of Drug Administration. London Wright, 1990 78-136. 

In recent years, much of the research work in the pharmaceutical sciences was focused on the development of effective vehicle systems, such as micelles, microemulsions, and liposomes, for drugs that are critical with respect to bioavailability. Knowledge of this subject is a prerequisite to developing vehicle systems for special administration routes, such as dermal, transdermal, intravenous, and nasal. 

The development of the first transdermal patches in the 1980s generated considerable interest in this route of drug administration. Soon afterwards, iontophoresis was rediscovered and its potential to contribute to the new field of transdermal drug delivery was examined. This work provided the basic principles for modern iontophoretic devices [13,18-21]. Furthermore, and importantly, they demonstrated the existence of a (primarily) electroosmotic, convective solvent flux during transdermal iontophoresis [10,11,22-24], and it was shown that the permselective properties of the skin (a) could be exploited to enhance the transport of neutral, polar species and (b) have a clear impact on ionic transport. Subsequent research has better characterized skin permselectivity and the factors which determine the magnitude of electroosmosis [25-27],... 

Parenteral administration Administration of drugs by routes other than via the alimentary canal by injection, transdermally, topically, and so on. 

Transdermal drug delivery is an attractive route of drug administration and will continue to proliferate in the following years. In the developmental stages it is important to have predictive models and to be able to identify suitable drug candidates. Although still in its infancy, the approach described above can be used predictively and as the mechanisms involved in percutaneous absorption are better understood and quantified the model can be refined accordingly. 

One of the key pieces to development of a successful drug product is the ability to deliver the drug to the site of action with minimal discomfort or inconvenience to the patient. For small molecule therapeutics, there is a wide range of options available for drug administration. Delivery via injection (IV, IM, and SC), oral, nasal, ocular, transmucosal (buccal, vaginal, and rectal), and transdermal routes is possible with small molecule drugs. However, the size of proteins and the complexity of their structures severely limit the routes of administration available to proteins. 

The administration of drugs by alternative routes avoids absorption and metabolic barriers that may be present in the GI tract. The routes can also provide systematic availability when oral administration is contraindicated due to a physiologic condition, or the route may provide for a concentration-time profile that approaches intravenous dosing profiles. The ophthalmic, nasal, pulmonary, buccal, transdermal, and rectal routes provide one or more of these advantages. 

Drugs chosen for delivery via a transdermal drug-delivery system must adequately penetrate the skin in such a way that the system determines the delivery rate that should be fairly constant. In addition, the drug must not irritate or sensitize the skin. It is hoped that in the future more drugs will be developed for transdermal delivery. This could become an alternative route for drug delivery to children who have difficulty with oral administration. 

The relatively non-invasive nature of transdermal drug delivery, and the fact that this route can simultaneously avoid problems associated with presystemic metabolism and mimic (at least, to some extent) parenteral input profiles, are significant advantages. There have been, therefore, diverse attempts to exploit the skin for peptide and protein delivery. As we have noted before, transdermal administration, with or without one or more enhancement technologies, will always be limited to potent drugs and this accounts, once more, for the effort devoted to peptide and protein (i.e., typically very active substances) administration via this route. 

Historically, the transdermal route of drug administration has been considered for topical rather than systemic delivery of drugs. Accordingly, most of the sonophoresis experiments reported in Table 2 were... 

Over the last 20 years, transdermal route of delivery has been considered as a means for systemic drug administration. Over this period, sonophoresis has been attempted to enhance systemic transdermal delivery. Levy et al. ° showed that 3-5 min of ultrasound exposure (IMHz, 1.5W/cm ) increased transdermal permeation of mannitol and physostigmine across hairless rat skin in vivo by up to 15-fold. They also reported that the lag time typically associated with transdermal drug delivery was nearly-completely eliminated after exposure to ultrasound. ° ... 

Eight routes of drug administration were discussed in detail oral, subcutaneous, intramuscular, intravenous, inhalation, intranasal, sublingual, and transdermal. A route of administration is selected according to the drug taken and the goals and circumstances of administration. 

For many pharmaceutical compounds administered as transdermal drug delivery systems, absorption can be assessed by determining the area under the curve (AUC) of the plasma concentration-time profile, the peak plasma flux, and time of peak flux, much as it is for determining bioavailability from oral and other routes of administration. These are classical metrics of biophar-maceutical bioequivalence studies and are extensively covered in other texts... 

Transdermal drug delivery is an approach used to deliver drugs through the skin for therapeutic use as an alternative to oral, intravascular, subcutaneous, and transmu-cosal routes. It includes the following categories of drug administration ... 

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