Drug absorption transdermal drugs

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

Nevertheless, there are reports on enhancement of ocular drug absorption by bile salts [33], surfactants [200], and chelators [149], Newton et al. [35] demonstrated that Azone, an enhancer widely tested in transdermal drug delivery [201], increased the ocular absorption of cyclosporine, an immunosuppressant, by a factor of 3, thereby prolonging the survival of a corneal allograft. In 1986, Lee et al. [34] reported that 10 pg/mL cytochalasin B, an agent capable of condensing the actin microfilaments, increased the aqueous humor and iris-ciliary body concentrations of topically applied inulin (5 kDa) by about 70% and 700%, respectively, in the albino rabbit. 

Generally, the stratum corneum is considered to be the rate limiting layer of the skin with regard to transdermal drug absorption. However, for the invasion of very lipophilic compounds, the bottleneck moves from the stratum corneum down to the viable, very hydrophilic layer of the epidermis, due to substances reduced solubility in this rather aqueous layer [14],... 

In many cases, transdermal drug absorption is investigated using a Franz-diffusion cell. The concentrations both in the membrane and the acceptor compartment are assumed to be zero at the start of the experiment. At different time points, the cumulative drug amount per unit area in the receptor q(t) is determined and plotted versus time t (Figure 20.1). After some time, the flux... 

Ho CK (2004) Probabilistic modeling of peracutaneous absorption for risk-based exposure assessments and transdermal drug delivery. Statistical Methodology 1 47-69... 

The barriers to drug absorption into the blood injections having the least and transdermal being the greatest ... 

There are several reasons for different routes of administration used in clinical medicine (Table 3-3)—for convenience (eg, oral), to maximize concentration at the site of action and minimize it elsewhere (eg, topical), to prolong the duration of drug absorption (eg, transdermal), or to avoid the first-pass effect. 

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. 

Because of the large surface area of the skin and its bypass of the liver as a first pass step in metabolism, many drug delivery systems have been developed that control the rate of drug delivery to the skin for subsequent absorption. Effective transdermal drug delivery systems of this type deliver uniform quantities of drug to the skin over a period of time. Technically, transdermal drug delivery systems may be classified into monolithic and membrane-controlled systems (9). 

Azone (l-Dodecylazacycloheptan-2-one) and related compounds have been studied as transdermal penetration and oral absorption enhancers. Although some efficacy has been shown, an emulsifying agent appears to be necessary for azone to penetrate the intestinal mucosal membrane in order to promote drug absorption. One study reported the absence of gross morphological damage after exposure of mucosa to azone but additional information on the effect of azone on overall mucosa structure is not avalable. 

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