Vehicles And Devices

For topical delivery of drugs, ointments, creams, lotions and gels are used. These materials have a long history but are not suitable for controlled transdermal delivery since they do not provide a protected reservoir of drug or a controlled area of application. There are at least four systems currently employed for systemic delivery of drugs (Figure 8.3). All of these have two main features; a reservoir containing the drug, and a physical mechanism to control the rate at which drug diffuses from the device. The first is the microsealed system, which is a partition-controlled delivery system containing a drug reservoir with a saturated suspension of drug in a water-miscible solvent homogeneously dispersed in a silicone elastomer matrix. A second device is the matrix-diffusion controlled system. The third and most widely used system for transdermal drug delivery is the membrane-permeation controlled system, in which diffusion across a polymer membrane controls the delivery rate. A fourth system, recently made available, is the gradient-charged system28. In many formulations the adhesive is spread across the entire face of the device and becomes part of the release rate control. This is considered to be a superior approach to simply using a ring of adhesive around the periphery, because it provides more reliable contact with the skin over the delivery area. The objective in designing all of these systems is to make the release rate from the device rate-

Transdermal Drug Delivery Device
Figure 8.3 Typical devices used for transdermal drug delivery

limiting so that individual physiological variations will not affect the absorption rate. This normally means that only small amounts of drug can be delivered, so the drug must be active in small doses.

The variety of devices, and means for absorption rate control, available is well illustrated by the products available for the transdermal delivery of nicotine, which is one of the most successful applications to date29. The Elan ProStep™ patch uses a hydrogel reservoir and absorption is controlled by skin permeability. The Ciba Habitrol™ patch and Cygnus-Kabi Nicotrol™ patch have polymer matrices containing nicotine, and release is controlled by diffusion through the matrix, which is slower than diffusion through the skin. The Alza Nicoderm™ patch also has a matrix reservoir but also uses a polyethylene membrane to control the release rate. This type of device provides protection against the most significant concern of the membrane-controlled devices, that the membrane would become ruptured and dose-dumping would occur. If the drug reservoir is held in a matrix then the release rate of this component can be engineered to be slightly higher than that of the membrane, so that it is not rate-limiting in the intact device, but provides protection in the event of membrane damage.

In the future we can expect to see an increasing number of more sophisticated devices produced by microtechnology. Altea Technologies is currently marketing a Micropor™ system which produces tiny pores of a few micrometres diameter in the stratum corneum using hot-wire technology. Henry et al30 have reported the use of microfabrication to produce arrays of microneedles which pierce the stratum corneum but are not long enough to trigger pain receptors. Technologies such as these have obvious extensions to delivery by iontophoresis and electroporation.

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