Supersaturated transdermal drug delivery systems, and methods for manufacturing the same

#This invention relates generally to drug delivery, and more particularly relates to supersaturated transdermal drug delivery systems, i.e., transdermal devices containing a supersaturated drug reservoir, and to methods for manufacturing such systems.

#The delivery of drugs through the skin provides many advantages; primarily, such a means of delivery is a comfortable, convenient and noninvasive way of administering drugs. The variable rates of absorption and metabolism encountered in oral treatment are avoided, and other inherent inconveniences--e.g., gastrointestinal irritation and the like--are eliminated as well. Transdermal drug delivery also makes possible a high degree of control over blood concentrations of any particular drug.

#Skin is a structurally complex, relatively thick membrane. Molecules moving from the environment into and through intact skin must first penetrate the stratum corneum. They must then penetrate the viable epidermis, the papillary dermis, and the capillary walls into the blood stream or lymph channels. To be so absorbed, molecules must overcome a different resistance to penetration in each type of tissue. Transport across the skin membrane is thus a complex phenomenon. However, it is the cells of the stratum corneum which present the primary barrier to absorption of topical compositions or transdermally administered drugs. The stratum corneum is a thin layer of dense, highly keratinized cells approximately 10-15 microns thick over most of the body. It is believed to be the high degree of keratinization within these cells as well as their dense packing which creates in most cases a substantially impermeable barrier to drug penetration.

#FIG. 1 illustrates in schematic form one embodiment of a solid matrix-type transdermal delivery system which may be manufactured so as to contain a supersaturated drug reservoir as provided herein.

#FIG. 2 illustrates in schematic form an alternative embodiment of a solid matrix-type transdermal delivery system which may be manufactured so as to contain a supersaturated drug reservoir as provided herein.

#FIG. 3 is a phase diagram constructed by evaluating melting temperature as a function of estradiol concentration, in the system of Example 1.

#Before describing the present invention in detail, it is to be understood that this invention is not limited to particular transdermal drug delivery device configurations, particular drug/vehicle formulations, or the like, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

#It must be noted that, as used in this specification and the appended claims, the singular forms "a", "an" and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to "a permeation enhancer" includes a mixture of two or more permeation enhancers, reference to "an excipient" or "a vehicle" includes mixtures of excipients or vehicles, reference to "an adhesive layer" includes reference to two or more such layers, and the like.

#Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although any methods and materials similar or equivalent to those described herein can be used in the practice for testing of the present invention, the preferred materials and methods are described herein.