Reservoir transdermal drug delivery system

Figure 2.9 Schematic of a reservoir transdermal drug-delivery system (A) and the drug-release rate obtained (B).

Passive transdermal drug delivery systems are more common. Passive transdermal systems have a drug reservoir containing a high concentration of drug adapted to contact the skin, where the drug... 

T.-E Chen, C.-M. Chiang, J. Jona, P. Joshi, and A. Ramdas, Polyurethane hydrogel drug reservoirs for use in transdermal drug delivery systems, WO Patent 1997009970 Al, 20 Mar 1997. 

Transdermal drug-delivery systems offer several important adventages over more traditional approaches, in addition to the benefits of avoiding the hepatic first-pass effect. Transdermal drug delivery systems (TDDS) are usually in the form of patches incorporating pressure sensitive adhesives. There are two basic designs for transdermal patches matrix or reservoir type. Matrix-type patches include monolithic adhesive and polymer matrices, whereas reservoir-type patches include liquid and solid-state reservoirs [71-73]. For various types of transdermal delivery systems, medical grade adhesive silicones are used as [73,74] ... 

FIGURE 10 Membrane-moderated transdermal drug delivery system (not to scale). Drug permeates from the patch reservoir through the protective outer layers of the skin and Is absorbed into the underlying capillaries of the general systemic blood circulation. 

Scopolamine was the first drug to be marketed as a transdermal delivery system (Transderm-Scop) to alleviate the discomfort of motion sickness. After oral administration, scopolamine has a short duration of action because of a high first-pass effect. In addition, several side-effects are associated with the peak plasma levels obtained. Transderm-Scop is a reservoir system that incorporates two types of release mechanims a rapid, short-term release of drag from the adhesive layer, superimposed on an essentially zero-order input profile metered by the microporous membrane separating the reservoir from the skin surface. The scopolamine patch is able to maintain plasma levels in the therapeutic window for extended periods of time, delivering 0.5 mg over 3 days with few of the side-effects associated with (for example) oral administration. 

As indicated in Fig. 1, a transdermal iontophoretic system requires that two electrode assemblies contact the patient s skin. The donor electrode (also known as the delivery or active electrode) contacts the drug reservoir. The counter electrode (also known as the return or receptor electrode) contacts the counter reservoir and completes the electrical circuit by providing a path for the current. The two reservoirs are separated from each other and contact skin over a fixed area. The electrodes apply an electric field across the skin by converting electric current supplied by the battery into ionic current moving in the skin and body. In doing so, a Faradaic reaction takes place at the electrode/ electrolyte interface. As described previously in this chapter, there is generally a linear dependence of the rate of drug delivery on this current. 

The microsealed delivery device is a variation of the matrix-type transdermal system in which the drug is dispersed in a reservoir phase which is then immobilized as discrete droplets in a cross-linked polymeric matrix. Release can be further controlled by inclusion of a polymeric microporous membrane. This system therefore combines the principles of both the liquid reservoir and matrix-type devices. Rate of release of a drug from a microsealed delivery system is dependent on the partition coefficient between the reservoir droplets and the polymeric matrix the diffusivity of the drug in the reservoir, the matrix and the controlling membrane and on the solubility of the drug in the various phases. There are, obviously, many ways to achieve the desired zero-order release rate, but only nitroglycerin has been commercially formulated into this type of delivery device (Karim 1983). 

Figure 9.2 Reservoir delivery systems based on rate-limiting polymer membranes. Rate-limiting polymer membranes can be used to produce several different types of drug delivery devices including (a) transdermal delivery systems, (b) planar con-trolled-release systems, and (c) cylindrical controlled-release systems.

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