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Transdermal Drug Delivery
By Merlin Goldman Transdermal drug delivery avoids many problems associated with the oral or intravenous routes: drastic pH changes, the presence of enzymes, variable transit times, pulse entry (rapidly fluctuating drug plasma concentrations), side effects, and inadequate patient compliance, while also eschewing needle delivery and its associated inconvenience and even patient phobia. There is a problem: the main function of skin is preventing things entering our body. However, a number of methods of bypassing this barrier have been found and the annual U.S. market for transdermal patches alone is more than $3 billion. Patches Patches applied to the skin eliminate the need for vascular access by syringe or the use of pumps. Transdermal patches were developed in the 1970s and the first was approved by the FDA in 1979 for the treatment of motion sickness. It was a three-day patch that delivered scopolamine. In 1981, patches for nitroglycerin were approved, and today there exist a number of patches for drugs such as clonidine, fentanyl, lidocaine, nicotine, nitroglycerin, oestradiol, oxybutinin, scopolamine, and testosterone. There are also combination patches for contraception, as well as hormone replacement. Depending on the drug, the patches generally last from one to seven days. The major advantages provided by transdermal drug delivery include the following: improved bioavailability, more uniform plasma levels, longer duration of action resulting in a reduction in dosing frequency, reduced side effects and improved therapy due to maintenance of plasma levels up to the end of the dosing interval compared to a decline in plasma levels with conventional oral dosage forms. Transdermal patches have been useful in developing new applications for existing therapeutics and for reducing first-pass drug-degradation effects. Patches can also reduce side effects; for example, oestradiol patches are used by more than a million patients annually and, in contrast to oral formulations, do not cause liver damage. Similarly, transdermal clonidine, nitroglycerin, and fentanyl patches exhibit fewer adverse effects than conventional oral dosage forms. In the mid-1980s, the pharmaceutical industry recognized the opportunity to develop a nicotine patch to help smokers give up. Although several factors influence whether attempts at smoking cessation are successful, addressing a smoker's physical addiction to nicotine increases the chances of additionally overcoming the psychological and emotional barriers. With approximately 50 million smokers in the U.S. at that time, of whom about one in three attempted to quit smoking each year, the potential market size for an effective smoking cessation aid was significant. The FDA approved all four nicotine patches within a few months at the end of 1991 and beginning of 1992; total sales during the first year of marketing approached $1 billion. Transdermal delivery surged into clinical practice and 'the patch' became a household word. Despite these successes, the number of drugs that can be administered using conventional patches is very limited. As evidence of this, all of the drugs presently administered across skin share three constraining characteristics: low molecular mass (‹500 Da), high lipophilicity (oil soluble), and small required dose (up to milligrams). The smallest drug presently formulated in a patch is nicotine (162 Da) and the largest is oxybutinin (359 Da). Opening the transdermal route to large hydrophilic drugs is one of the major challenges in the field of transdermal drug delivery. Gels Gels provide additional challenges to patches because the gel should combine both pharmaceutical and cosmetic qualities (consistency, color, and smell). However, gel technology has advantages over patch technology including cost, lack of irritancy associated with occlusion or response to adhesives, delivery efficiency, cosmetic elegance, potential for in-house manufacturing, and the ability to apply drug to a large surface area. Antares Pharma uses gel technology to address two applications: hormone delivery and active substances for the treatment of psoriasis, soft-tissue and local infections, and management of hair loss. The company has developed a transdermal, long-acting topical application for Hormone Replacement Therapy. AndroGel, the first transdermal testosterone gel for men, was launched in 2000. It is a hydroalcoholic gel which is absorbed through the skin and delivers testosterone to the patient for approximately 24 hours. The product is used by men with primary hypogonadism or hypogonadotropic hypogonadism and has annual sales of approximately $225 million. Other A number of other methods for delivering drugs across skin have also been studied. Similar to microneedles that pierce multiple holes into the surface of the skin, thermal methods have also been used to locally heat and ablate holes in stratum corneum, thereby increasing skin permeability. After a rise and fall in popularity in the mid-twentieth century, high-velocity jet injectors are receiving increased popularity. The aim now is on improved device designs for controlled, needle-free injection of drug solutions across the skin and into deeper tissue; insulin is delivered clinically by jet injection and jet injectors for other drugs are under development. A variation on this approach by PowderJect Pharmaceuticals propels solid drug particles into or across the skin, which is of special interest for vaccines. Jet injectors are presently on the market, and a number of companies are developing new devices. -------------------------------------------------------------------------------- © Merlin Goldman, www.magnetical.com Source: D&MD To view and purchase D&MD reports click here! |
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