Abstract: Method and laminated composite for administering short or intermediate half-life benzodiazepines such as alprazolam or triazolam transdermally to treat conditions such as anxiety in the case of alprazolam and insomnia in the case of triazolam. The composite comprises an impermeable backing layer and a reservoir layer containing the benzodiazepine and a permeation enhancer combined with a solvent-based acrylic polymer adhesive with the amounts of benzodiazepine and enhancer being sufficient to cause the benzodiazepine to pass through the skin at a rate in excess of about one .mu.g/cm.sup.2 /hr.

Abstract: Pharmaceutical formulations, transdermal drug delivery devices, and methods of drug delivery using the formulations and devices of the invention are disclosed which make it possible to enhance the rate of transdermal drug delivery of pharmaceutically active compounds and in particular molsidomine. The rate of drug delivery is increased by using absorption promoters which include monoalkyl phosphates and salts thereof alone or in combination with other absorption promoters such as polyhydroxyl esters, longchain fatty acids, polyhydroxyl alcohols and terpenes. Particular combinations of monoalkyl phosphates with one or more additional absorption promoters provides synergistic effects with respect to enhancing the rate of drug delivery of certain pharmaceutically active drugs such as molsidomine.

Abstract: A transdermal drug delivery device that administers drug in an initial pulse followed by a substantially lower continuous rate comprising a drug reservoir of the drug dissolved in a carrier and a volatile permeation enhancer confined between a backing that is permeable to the volatile permeation enhancer and an underlying substrate layer that is permeable to the drug, carrier and enhancer. When the device is placed on the skin the volatile permeation enhancer is depleted from the reservoir by evaporation through the backing such that the magnitude and duration of the pulse is dependent upon the permeability of the backing layer to the volatile enhancer.

Abstract: A method for enhancing the permeability of the skin or other biological membrane to a material such as a drug is disclosed. In the method, the drug is delivered in conjunction with ultrasound having a frequency of above about 10 MHz. The method may also be used in conjunction with chemical permeation enhancers and/or with iontophoresis.

Abstract: Pharmaceutical formulations, transdermal drug delivery devices, and methods of drug delivery using the formulations and devices of the invention are disclosed which make it possible to enhance the rate of transdermal drug delivery of pharmaceutically active compounds and in particular molsidomine. The rate of drug delivery is increased by using absorption promoters which include monoalkyl phosphates and salts thereof alone or in combination with other absorption promoters such as polyhydroxyl esters, longchain fatty acids, polyhydroxyl alcohols and terpenes. Particular combinations of monoalkyl phosphates with one or more additional absorption promoters provides synergistic effects with respect to enhancing the rate of drug delivery of certain pharmaceutically active drugs such as molsidomine.

Abstract: A delayed onset transdermal drug delivery device exhibiting a delay period of at least six hours comprising a laminated composite of (12) a top backing layer; (13) a pressure rupturable layer underlying (12); (14) a reservoir of a solution of drug in a liquid vehicle between (12) and (13); (16) a wick layer underlying (13) for dispersing the drug once (13( is ruptured; (17) a polymer layer underlying (16) that is permeable to the drug; (18) a microporous membrane underlying (17) which is itself impermeable to the drug but whose pores are filled with a polymer that is immiscible in the adhesive and has a solubility parameter within two units of the solubility parameter of the vehicle; and (20) an adhesive layer underlying (18) that is permeable to the drug but is immiscible in the polymer filling the pores of (6).

Abstract: A delayed onset transdermal drug delivery device exhibiting a delay period of at least eight hours comprising a laminated composite of (12) a top backing layer; (13) a pressure rupturable layer underlying (12); (14) a reservoir of a solution of drug in al liquid vehicle between (12) and (13); (16) a wick layer underlying (13) for dispersing the drug once (13) is ruptured; (17) a first adhesive layer underlying (16) that is permeable to the drug; (18) a first polymer membrane that is permeable to drug but substantially impermeable to the adhesive of (17); (19) a microporous membrane underlying (18) which is itself impermeable to the drug and whose pores are unfilled; (20) a second polymer membrane that underlies the microporous membrane that is permeable to drug but substantially impermeable to the adhesive of (21) below; and (21) a second adhesive layer underlying (20) that is permeable to the drug.

Abstract: A transdermal delivery device has a reservoir containing an active compound, which is kept separate from the delivery layers of the device until administration. At the time of administration, the reservoir is laminated to the delivery layers, or is ruptured to place the active compound, vehicle, and/or permeation enhancers in contact with the delivery layers, which results in administration of the active compound to the skin after a delay period.

Abstract: A matrix for containing drugs for transdermal delivery systems is disclosed. The matrix, formed of a skin-adhesive acrylate copolymer, attains high rates of drug delivery without the addition of drug delivery rate enhancers. In preferred embodiments the matrix is used to administer steroids, in particular estradiol. Water-soluble polymers may be added as well.

Abstract: Method and laminated composite for administering lisuride transdermally to treat conditions such as Parkinson's disease. The composite comprises an impermeable backing layer and a reservoir layer containing lisuride and a permeation enhancer combined with a pressure-sensitive adhesive with the amounts of lisuride and enhancer being sufficient to cause the lisuride to pass through the skin at a rate in excess of about one mcg/cm.sup.2 /hr.

Abstract: Multi-day skin patches for administering bimakalim transdermally to treat cardiovascular diseases are described which consist of laminated composites having an occlusive elastomeric polymer backing layer and an underlying reservoir layer composed of a solid matrix of bimakalim dispersed in a polydimethylsiloxane or acrylate adhesive. The skin flux of bimakalin from the patches is greater than 0.1 .mu.g/cm.sup.2 /hr.

Abstract: Improved transdermal drug delivery systems are provided which contain an occlusive, elastomeric backing layer which is preferably liquid-resistant. The systems contain as a backing layer a single homogeneous sheet of an elastomeric material having a moisture vapor transmission rate ("MVTR") in the range of about 0.1 to 20 g/m.sup.2 /hr and a Young's modulus in the range of about 10.sup.4 to 10.sup.9 dynes/cm.sup.2. Methods for making and using transdermal drug delivery devices containing such backing layers are provided as well.

Abstract: A delayed onset transdermal drug delivery device exhibiting a delay period of at least six hours comprising a laminated composite of (1) a top backing layer; (2) a pressure rupturable layer underlying (1); (3) a reservoir of a solution of drug in a liquid vehicle between (1) and (2); (4) a wick layer underlying (2) for dispersing the drug once (2) is ruptured; (5) a first adhesive layer underlying (4) that is permeable to the drug; (6) a microporous membrane underlying (5) which is itself impermeable to the drug and whose pores are substantially unfilled prior to application of the device to the skin; and (7) a second adhesive layer underlying (6) that is permeable to the drug but is immiscible in the polymer filling the pores of (6).

Abstract: A method for enhancing the permeability of the skin or other biological membrane to a material such as a drug is disclosed. In the method, the drug is delivered in conjunction with ultrasound having a frequency of above about 10 MHz. The method may also be used in conjunction with chemical permeation enhancers and/or with iontophoresis.

Abstract: Method and laminated composite for administering lisuride transdermally to treat conditions such as Parkinson's disease. The composite comprises an impermeable backing layer and a reservoir layer containing lisuride and a permeation enhancer combined with a pressure-sensitive adhesive with the amounts of lisuride and enhancer being sufficient to cause the lisuride to pass through the skin at a rate in excess of about one mcg/cm.sup.2 /hr.

Abstract: Methods and compositions are provided which increase the permeability of skin to transdermally administered pharmacologically active agents. The compositions are formulated with one or more vegetable oils as skin permeation enhancers; a preferred composition contains both coconut oil and soybean oil. Drug delivery systems for administering drugs transdermally in combination with the vegetable oil-based enhancer compositions are provided as well.

Abstract: Method and laminated composite for administering short or intermediate half-life benzodiazepines such as alprazolamine or triazolam transdermally to treat conditions such as anxiety in the case of alprazolam and insomnia in the case of triazolam. The composite comprises an impermeable backing layer and a reservoir layer containing the benzodiazepine and a permeation enhancer combined with a solvent-based acrylic polymer adhesive with the amounts of benzodiazepine and enhancer being sufficient to cause the benzodiazepine to pass through the skin at a rate in excess of about one .mu.g/cm.sup.2 /hr.

Abstract: Transdermal administration of dexmedetomidine, the dextrorotatory isomer of medetomidine, is described. The method involves sedating a patient by administering dexmedetomidine to a predetermined area of skin at an administration rate and for a time period effective to achieve the desired level of sedation. A therapeutic system for transdermally administering the drug is also provided. The therapeutic system is in the form of a skin patch which is a laminated composite of a backing layer, an optional anchor adhesive layer, a contact adhesive layer, and one or more additional layers.

Abstract: A laminated composite for administering fentanyl transdermally that consists of a fentanyl-impermeable occlusive backing layer and an adhesive fentanyl reservoir layer comprising fentanyl dissolved in an amine-resistant polydimethylsiloxane that has a high diffusivity and poor solubility for fentanyl which enables the fentanyl to be released rapidly from the composite over a one day period with little residual fentanyl left in the reservoir thereafter.

Abstract: Transdermal administration of dexmedetomidine, the dextrorotatory isomer of medetomidine, is described. The method involves sedating a patient by administering dexmedetomidine to a predetermined area of skin at an administration rate and for a time period effective to achieve the desired level of sedation. A therapeutic system for transdermally administering the drug is also provided. The therapeutic system is in the form of a skin patch which is a laminated composite of a backing layer, an optional anchor adhesive layer, a contact adhesive layer, and one or more additional layers.