Transdermal formulations

Nitrate products are available in both oral and transdermal formulations for chronic use. Commonly used products are listed in Table 4-8. All nitrate products are equally effective at preventing the recurrence of angina when used appropriately. 

Dermatological and Transdermal Formulations, edited by Kenneth A. Walters... 

The MAOIs are as effective as the heterocyclic antidepressants and the newer agents, such as the SSRIs. However, at least two forms of life-threatening toxicity (hepatotoxicity and dietary tyramine-induced hypertensive crisis ) have been associated with their chronic use. For this reason, the MAOIs are not considered first-line agents in the treatment of depression. They are generally reserved for treatment of depressions that resist therapeutic trials of the newer, safer antidepressants. However, a new transdermal formulation of selegiline undergoing clinical trials demonstrates antidepressant efficacy without concerns of liver toxicity or dietary tyramine-induced hypertension. 

DESIGNING A HIGH-THROUGHPUT SCREENING ASSAY FOR TESTING TRANSDERMAL FORMULATIONS... 

Any high-throughput assay used for screening of transdermal formulations should meet the following requirements ... 

Karande P, Mitragotri S. High throughput screening of transdermal formulations. Pharm Res 2002 19 655-660. 

Ethanol is used in many transdermal formulations and is often the solvent of choice for incorporation into patches. As with water, ethanol permeates rapidly through human skin with a steady-state flux of approximately 1 mg/cm2/h [31]. 

Similarly, topical targeting techniques (including advanced aerosol systems and dermal or transdermal formulations) have been introduced or are about to be introduced that provide prolonged localized delivery or alternative means of systemic delivery. Both pose problems of a different kind (and perhaps magnitude), depending on whether the lungs or the skin, respectively, are the site of action or the portal of entry for systemic delivery. 

EP 123469 (Lilly appl. 6.4.1984 USA-prior. 8.4.1983). novel transdermal formulations ... 

The local anesthetic lidocaine provides significant relief of neuropathic pain in the clinic when administered systemically at subanesthetic doses. In several placebo-controlled studies, intravenous infusions of lidocaine significantly reduced neuropathic pain at plasma concentrations of 1.5-5 pgmL 1 [59-61]. Lightheadedness is a common side effect at therapeutic doses, whereas cardiac depression is associated with plasma concentrations of 20-25 xgmL 1. A transdermal formulation of lidocaine is approved in the United States for the treatment of postherpetic neuralgia [62]. Orally available state-dependent Nayl blockers have shown efficacy in the clinic when appropriate plasma concentrations are achieved. 

There is a wide variety of transdermal systems on the market at present. These patches are diversely referred to as reservoir , monolithic , membrane-controlled , adhesive , matrix , and so on. Unfortunately, these terms are not always used consistently and, worse, they are sometimes used inaccurately. In all cases, however, the idea is that the system offers a means to hold a payload of the drag and a configuration (or platform ) to ensure presentation of the active agent to the skin surface at a rate sufficient to ensure a systemic pharmacological effect after the drag has crossed the skin s barrier. Most simplistically, one can divide the transdermal formulations presently available into three categories (Figure 8.3) ... 

These testosterone systems illustrate two different approaches to solve the problem of inadequate percutaneous absorption rate. In the former case, the patch must be applied to the body s most permeable skin site, the scrotum (which has been shown to be at least five times more permeable than ary other site). In the latter, the difficulty is resolved by creating a transdermal formulation which includes excipients to reduce barrier function. Neither solution is ideal scrotal application is clearly not preferred from a patient compliance standpoint on the other hand, permeation enhancers, by their very nature, tend to be irritating (and the more effective they are, the greater the irritation they provoke). This general problem, which presently limits the application of transdermal delivery, is now discussed in more detail. 

Transdermal formulations may be preferred as they require a lower dose (and hence have lower risk) as they do not undergo the first-pass effect in the liver - although patient preference is usually based on convenience. 

Misra, A., et al. (1997), Biphasic testosterone delivery profile observed with two different transdermal formulations, Pharm. Res., 14(9), 1264-1268. 

Transdermal formulations of estradiol are available. They can be effective and convenient for women who dislike taking oral therapy. Both oestradiol and oestriol can be taken vaginally as a cream, ring, pessary or tablet. 

If absorption is slow, and the apparent absorption half-life is much longer than the elimination half-life, then the dose regimen can be based on the apparent half-life of the absorption phase. Changing the formulation is a relatively common approach that is taken for short-acting drugs to extend the duration of absorption. The elimination half-life of nitroglycerin is approximately 2 min. However, nitroglycerin from a transdermal formulation is slowly released, and therapeutic plasma concentrations can be maintained for 24 h. 

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