Transdermal reservoir systems

It should be noted that at least two distinctly different types of transdermal patches or systems exist. One of these is the (liquid) reservoir system. The other is the matrix system. These systems differ both in their manufacturing steps and in their final product presentation. Key manufacturing steps for both systems are illustrated in Figure 1. 

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). 

Such design criteria have been successfully utilized in commercially available membrane-reservoir type of transdermal delivery systems for scopolamine, nitroglycerin, and more recently, estradiol (40,41). 

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. 

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). 

A schematic diagram of a transdermal iontophoretic system on skin is shown in Fig. LA source of electrical energy, such as a battery, supplies electric current to the body through two electrodes. The first electrode, called the donor electrode, delivers the therapeutic agent into the body. The second electrode, called the counter or receptor electrode, closes the electrical circuit. Each electrode contacts an ionically conductive reservoir, normally present as a liquid or hydrogel. The reservoirs are placed on the patient s skin and contain either the drug (for the donor electrode assembly) or a biocompatible electrolyte (for the counter electrode assembly). 

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. 

Fentanyl transdermal delivery systems (FTDS) use an unsealed multilaminate system containing a solid matrix, in which fentanyl is embedded instead of the reservoir designed in the TTS. FTDS is not to be recommended for routine postoperative pain treatment, even though it has a faster onset of action (4—6 hours) after cases of fentanyl toxicity, especially respiratory depression. FTDS has not been investigated adequately in chronic pain and is not expected to be superior to the TTS technique. 

Figure 1.1 A drawing of a typical transdermal patch system to deliver drug into the systemic circulation by way of the skin. Drawn here is the system with (1) a reservoir containing the drug adsorbed to (2) lactose particles in (3) an oil (4) the ratecontrolling membrane, a copolymer whose thickness and composition are altered to achieve the desired rate of transport of the drug and (5) the adhesive layer, also a polymer, although liquid, which attaches the patch to the skin. The basic structure of the skin (6) illustrates the routes of penetration of the drug through this barrier layer into the systemic circulation via the capillary blood supply (7).

Rgure 9.27 The four main types of transdermal patch matrix, reservoir, multilaminate and drug-in-adhesive designs. The matrix/reservoir systems are cut away to show the drug. Illustration courtesy of 3M. 

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.

One of these types is the membrane-controlled transdermal therapeutic system, which is outlined in Figure 18.12. These systems consist of the following parts i) covering membrane, ii) drug reservoir, iii) micropore membrane controlling drug delivery, and iv) adhesive contact surface. (Further types of transdermal systems are going to be described in Chapter 16.2.4.3.3). The most commonly used membranes are polyethylene vinyl acetate and polyethylene [60-62]. 

There are several available transdermal therapeutic systems including reservoir membrane designs and, as will be discussed in subsequent sections, matrix designs. A typical reservoir transdermal therapeutic system is shown in Figure 16. 

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] ... 

The Transdermal Therapeutic System-scopolamine, shown schematically in Figure 3, is a multilayer laminate. It is comprised of a steady-state drug reservoir containing scopolamine in a polymeric gel, sandwiched between an impermeable backing membrane and a rate-controlling, microporous membrane. On the dermal side of the rate-controlling mem-... 

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