Transdermal systems limitations

Within the last 10, years several new compounds were launched in the field of non-steroidal antiinflammatory drugs (NSAIDs) with a clear focus on cyclooxygenase type 2 selective compounds. In the field of opioids on the other hand no new drugs have passed phase III clinical trials. In this field innovation has been achieved through new pharmaceutical formulations of known drugs such as transdermal systems, e.g. buprenorphine patch, transmucosal systems, e.g. fentanyl lollipop, or rectal delivery systems containing e.g. morphine. These were developed in order to reduce opioid side effects, but also to overcome pharmacokinetical limitations, in particular to prolong compliance and duration of action. 

This very powerful analgesic had been limited to parenteral use during and after surgery. Accurate dose titration is necessary because of the drug s very narrow therapeutic window (1-2 ng mL ). The potential of fentanyl, however, to significantly improve the treatment of acute post-operative pain and chronic cancer pain provoked the development of the now-approved Duragesic transdermal system. This reservoir system can be used for up to 3 days and is available in four doses (10, 20, 30 and 40 cm2 delivering, respectively, 25, 50, 75 and 100 pg hr 1). 

Given the limitations imposed on transdermal systemic drug delivery by the barrier properties of the stratum corneum, new technologies have attempted to completely bypass this obstacle by either the creation of a physical conduit (microneedles) or direct powder delivery via compressed gas. The Alza Corporation technology (Macroflux ) comprises a patch system that contains a microprojection array designed to create superficial microchannels across the stratum corneum.When used in conjunction with their electrotransport system, the Macroflux system provides controlled in vivo delivery of therapeutic doses of... 

The WEDD transdermal system does not apply a high enough electrical potential to generate the electric current commonly observed in transdermal iontophoresis. Although the electric field may provide some flux enhancement, flux enhancement due to the electric current in this system is limited. The system therefore may not be viewed as a transdermal iontophoresis system. 

Given the complexity of some of the dosage forms mentioned earlier, this guidance was limited to solid oral dosage forms, liquid oral dosage forms, and parenterals (small and large volume). These products serve as models, and the principles applied can be used for all other dosage forms such as inhalation products, topical formulations, and transdermal systems. 

Despite the limitations imposed by the physiology of the skin, several marketed controUed release transdermal dmg dehvery systems are available in the United States for example, scopolamine [51-34-3] for the treatment of motion sickness, nitroglycerin [55-63-0] for angina, estradiol [50-28-2] for the rehef of postmenopausal symptoms and osteoporosis, clonidine [4205-90-7] for the treatment of hypertension, fentanyl [437-38-7] as an analgesic, and nicotine [54-11-5] as an aid to smoking cessation. These systems are designed to dehver dmg for periods of one to seven days. 

Industrial environments expose individuals to a plethora of airborne chemical compounds in the form of vapors, aerosols, or biphasic mixtures of both. These atmospheric contaminants primarily interface with two body surfaces the respiratory tract and the skin. Between these two routes of systemic exposure to airborne chemicals (inhalation and transdermal absorption) the respiratory tract has the larger surface area and a much greater percentage of this surface exposed to the ambient environment. Or dinary work clothing generally restricts skin exposures to the arms, neck, and head, and special protective clothing ensembles further limit or totally eliminate skin exposures, but breathing exposes much of the airway to contaminants. 

Purdon C, Azzi C, Zhang J, Smith E, Maibach H. Penetration enhancement of transdermal delivery—current permutations and limitations. Crit Rev Ther Drug Carrier Systems 2004 21 97-132. 

The use of therapeutic proteins is growing rapidly and it has been suggested that this class of drugs may soon represent a significant fraction of the pharmaceutical market [45]. There is an urgent need for the development of delivery systems for proteins because, so far, the use of therapeutic proteins is limited to their low oral and transdermal bioavailability. 

Nicotine dependence may respond to replacement therapy with either nicotine gum or transdermal patches, and detoxification from nicotine dependence has been described using clonidine. Bupropion, an antidepressant, also shows efficacy for smoking cessation. The nicotinic receptor blocker mecamylamine, which has good central nervous system access, has been used with limited efficacy. Overall, success rates for smoking abstinence at 1 year are about 20%, with even less success for depressed smokers. 

Parenteral delivery systems involve the use of needles. This is painful for the patient, as well as generally requiring the intervention of medical professionals. The oral route, which involves merely swallowing a tablet, liquid or capsule, thus represents a much more convenient and attractive route for drag delivery. Transdermal patches are also well accepted by patients and convenient. Some other dosage forms, for example nebulizers, pessaries and suppositories, may meet with more limited patient compliance. 

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