Transdermal delivery agents

Transdermal delivery is a noninvasive intravenous infusion of drug to maintain efficacious drug levels in the body for predictable and extended duration of activity. Diffusion-controlled transdermal systems are designed to deliver the therapeutic agent at a controlled rate from the device to and through the skin into the systemic circulation. This route of administration avoids unwanted presystemic metabolism (first-pass effect) in the GI tract and the liver. Patient satisfaction has been realized through decreased... 

The oxazolidinone-based compounds are the most common (Figure 23.1), and examples include antibacterial,27-28 adhesion receptor antagonists,29-30 tumor necrosis factor inhibitors,31 platelet aggregation inhibitors,32 antimigraine drugs,33 and monoamine oxidase inhibitors.3435 In one case, an oxazolidinone has been used as a transdermal drug delivery agent.36... 

Membrane-reservoir systems based on solution-diffusion mechanism have been utilized in different forms for the controlled delivery of therapeutic agents. These systems including membrane devices, microcapsules, liposomes, and hollow fibres have been applied to a number of areas ranging from birth control, transdermal delivery, to cancer therapy. Various polymeric materials including silicone rubber, ethylene vinylacetate copolymers, polyurethanes, and hydrogels have been employed in the fabrication of such membrane-reservoir systems (13). 

The selection of a vehicle can dramatically affect delivery and consequently efficacy of topical preparations. In terms of transdermal delivery, where delivering therapeutic agents for systemic effects is desired, solvents and co-solvent systems are widely used to improve both the amount and range of drugs that can be administered at therapeutic levels through the skin. Vehicles used in transdermal systems, such as patches, have recently been reviewed (Williams, 2003). In contrast, the focus of this chapter is on the use of solvents in topical dosage forms, i.e. preparations intended for a local or regional effect on the skin. 

Arecoline is of historical interest, because its structure, like those of many other early medicinal agents, viras determined and confirmed by a 19th-century German pharmacist, E. Jahns (2). Xanomeline may be viewed as a nonclassical bio-isostere of the ester moiety of arecoline. It is a muscarinic M1/M4 agonist that is showing promise in clinical trials for the treatment of Alzheimer s disease (35). Although it is not tolerated at orally effective doses, transdermal delivery systems are showing promise. 

Clonidine hydrochloride is used in the treatment of grades of hypertension. The usual initial dose of clonidine hydrochloride is 50 to 100 pg orally thrice daily increased every second or third day according to the response of the patient. The usual maintenance dose is 0.3 to 1.2 mg daily but doses of up to 1.8 mg or more daily may be required. To reduce side effects a similar dose of clonidine may be given in conjunction with a thiazide diuretic but combination with a 13-blocking agent should be avoided where possible clonidine may also be given in a sustained-release formulation which enables twice-daily dosage, or by a transdermal delivery system which is applied once a week and delivers 100-300 pg daily at a constant rate (4). 

Microemulsions have gained a considerable interest in deep dermal and transdermal delivery of an array of therapeutic agents. The local anesthetic, Lidocaine, has reached commercialization for delivery (94). 

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. 

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