Transdermal drug delivery membrane-controlled systems

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). 

Ethylene vinyl acetate copolymers are used as membranes and backings in laminated transdermal drug delivery systems. They can also be incorporated as components in backings in transdermal systems. Ethylene vinyl acetate copolymers have been shown to be an effective matrix and membrane for the controlled delivery of atenolol triprolidine, and furose-mide. The system for the controlled release of atenolol can be further developed using ethylene vinyl acetate copolymers and plasticizers. ... 

Membrane permeation-controlled transdermal drug delivery (Fig. 5.2) has been successfully applied in therapeutic systems for scopolamine (prevention of motion sickness for a 3-day period), nitroglycerin (prophylaxis against attack of angina pectoris over a 24-h period), clonidine (control of hypertension for a 7-day period), and fentanyl (control of constant pain for 72 h). 

Figure 18.12 The cross-section view of a membrane controlled transdermal drug delivery system, showing various major structural components [59].

The majority of controlled drug delivery systems now being marketed or under development are based on diffusion of the drug through a semipermeable membrane to achieve the requisite release rate. Diffusion control is particularly important to transdermal delivery, where biodegradation and dissolution are not viable mechanisms of controlling the release rate. Provided the process is Fickian, the rate of diffusion through the semipermeable polymer is determined by... 

Figure 8.34 Examples of drug-delivery systems employing polymeric membranes, (o) Ocusert system for the eye with two rote-controlling membranes, (b) Tronsiderm system for transdermal medication with one rote-controlling layer, (c) The Progestasert device for intrauterine insertion in which the body of the device serves as the rote-controlling barrier, (d) The oral Oros device in which the membrane is o semipermeable membrane which forbids drug transport, allowing water ingress only.

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.

In membrane diffusion systems the polymer membrane with a given pore size or pore size distribution controls the diffusion of the active substance from the drug reservoir. Dosage forms with membrane-controlled drug delivery can be coated tablets, coated granules or pellets, or so-called multiparticulate systems on which various coats are applied. One possibility for transdermal drug administration is the transdermal patch controlled with a membrane [4-7,34-39]. 

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]. 

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