The parameters for ideal candidates can be divided into physicochemical properties, biological characteristics, and polymer variables.
- The drug should have a molecular weight less than approximately 1000 Daltons.
- The drug should have affinity for both lipophilic and hydrophilic phases. Extreme partitioning characteristics are not conducive to successful drug delivery via the skin.
- The drug should have a low melting point.
- Since the skin has a pH of 4.2 to 5.6, solutions within this pH range are used to avoid damage to the skin. However, for a number of drugs, there may also be significant transdermal absorption at pH values at which the unionized form of the drug is predominant.
- The drug should be potent with a daily dose of the order of a few mg/day.
- The half-life of the drug should be short.
- The drug should be non-irritating and non-allergic.
- Drugs that degrade in the GI tract or are inactivated by hepatic first-pass effect are suitable candidates for transdermal delivery.
Advances in transdermal drug delivery technology have been rapid because of sophisticated polymer science that allows incorporation of polymers in transdermal systems in adequate quantity. The release rate from transdermal systems can be tailored by varying polymer composition. Selection of a polymeric membrane is important in designing a variety of membrane-permeation controlled transdermal systems.
- The polymer should be chemically nonreactive or an inert drug carrier.
- The polymer must not decompose on storage or during life span.
- Molecular weight, physical characteristic, and chemical functionality of the polymer must allow the diffusion of the drug substance at a desirable rate.
- The polymer and its decomposed product should be nontoxic. It should be biocompatible with skin.
- The polymer must be easy to manufacture and fabricate into desired products. It should allow incorporation of large amounts of active agent.
Silicone elastomer blend networks, sugar siloxanes, amphiphilic resin linear polymers, and silicone hybrid pressure sensitive adhesives are showing promise for potential performance advantages and improved drug delivery efficacy.
Early on, transdermal delivery systems were used mainly for delivery of small, lipophilic, low-dose drugs. More recently, delivery systems began using chemical enhancers, non-cavitational ultrasound, and iontophoresis to enhance the efficacy of transdermal patches. Today, the ability of iontophoresis to control delivery rates in real time is providing added functionality in a number of instances.
At the same time, microneedles combined with thermal ablation are progressing through clinical trials for delivery of macromolecules and vaccines, including insulin, parathyroid hormone, and influenza. With these enhancement strategies, transdermal delivery is poised to significantly impact drug delivery choices.
Both chemical enhancers and the newest physical enhancers (ultrasound, thermal ablation, and microneedles) have begun expanding transdermal delivery of macromolecules and vaccines. These scientific and technological advances enable targeted disruption of the stratum corneum while protecting deeper tissues, positioning all types of transdermal drug delivery to have a widespread impact on medicine.
This article was written by Luis Tissone, Director of Life Sciences, Trelleborg Sealing Solutions, Fort Wayne, IN. For more information, Click Here .>