Abstract: The invention provides a local concentration management system (LCMS) for delivery of highly concentrated therapeutic agent formulations. The LCMS comprises a device comprising an elongate body defining a lumen between its proximal and distal ends, and a diffuser element, a dilutor element, or both. The diffuser element, which is selectively permeable to the agent, is operatively associated with the elongate body so that agent flows through the elongate body, and into and through the diffuser element to exit the system. The dilutor element can be operatively associated with the system to be in fluid communication with the elongate body lumen, a diffusion space defined by a diffuser element inner wall, or both. The dilutor element is selectively water permeable, but substantially impermeable to agent, to provide for dilution of the agent during transit through the system. The LCMS system is designed to disperse and/or dilute the drug delivery stream.

Abstract: Dosage forms and drug delivery devices suitable for administration of pharmaceutical compounds and compositions, including the oral drug administration of compounds.

Abstract: Transdermal delivery systems for administering sufentanil through the skin are provided. The systems contain a sufficient amount of sufentanil to induce and maintain a constant state of analgesia when applied to a subject. The systems are characterized as having one or more features including a high degree of dosage form rate control over flux of sufentanil from the system, a high net flux of sufentanil from the system through the skin, lack of a permeation enhancer, an adhesive member demonstrating superior shear time, a low coefficient of variation in the net flux of sufentanil from the system, a high delivery efficiency, and a substantially constant steady state net flux of sufentanil from the system. Methods of using the transdermal delivery systems to administer a sufficient amount of sufentanil to induce and maintain analgesia for extended periods when applied to a subject are also provided.

Abstract: Composition of matter for application to skin to administer fenoldopam by permeation through the skin, the composition comprising fenoldopam to be administered, at a therapeutically effective rate, in combination with a permeation enhancer or mixture. Also disclosed are drug delivery devices and methods for the transdermal administration of fenoldopam for the treatment of hypertension, congestive heart failure, and chronic and acute renal failure.

Abstract: The invention features a plug for use with a drug delivery device, wherein the plug defines an expansion control channel, which accommodates thermal expansion of a formulation in a reservoir of a drug delivery device, and an exit channel. In one embodiment, the plug comprises an inner plug member and an outer plug member, which members define an expansion control channel to facilitate release of entrapped air and to accommodate thermal expansion of formulation from the sealed drug reservoir. The plug further defines an exit channel, and may optionally further comprise a frit positioned within the flow pathway just prior to the delivery outlet, or both.

Abstract: The invention features devices and methods for treatment of pain. The drug delivery device is a drug delivery system adapted for whole implantation in a subject and to provide pain relief by delivery of fentanyl or a fentanyl congener (e.g., sufentanil) over a protracted period of time (e.g., at least 3 days or more than 3 days). The device comprises a housing defining a reservoir that contains a drug formulation, a pump operatively connected to the housing so as to facilitate movement of drug out of the reservoir and out of the device, and a thermal expansion element which defines a flow pathway comprising a thermal expansion channel to accommodate thermal expansion of formulation in the reservoir. The device can further comprise a valve positioned within the flow pathway so as to prevent movement of drug out of the reservoir prior to use.

Abstract: Composition of matter for application to a body surface or membrane to administer pergolide by permeation through the body surface or membrane, the composition comprising pergolide to be administered, at a therapeutically effective rate, alone or in combination with a permeation enhancer or mixture. Also disclosed are drug delivery devices containing the pergolide or pergolide and enhancer composition and methods for the transdermal administration of the pergolide and pergolide/enhancer composition.

Abstract: The present invention provides devices and methods for delivery of very low dosages to the inner ear. The device is a self-contained unit that reproducibly and consistently delivers a dose of therapeutic agent that is effective, yet below the ototoxic threshold for that agent. The invention further provides therapeutic methods using the device of the invention.

Abstract: Dosage forms and drug delivery devices suitable for administration of pharmaceutical compounds and compositions, including the oral drug administration of compounds.

Abstract: Composition of matter for application to a body surface or membrane to administer fenoldopam by permeation through the body surface or membrane, the composition comprising fenoldopam to be administered, at a therapeutically effective rate, in combination with a permeation enhancer or mixture. Also disclosed are drug delivery devices and methods for the transdermal administration of fenoldopam for the treatment of hypertension, congestive heart failure, and chronic and acute renal failure.

Abstract: Composition of matter for application to a body surface or membrane to administer fenoldopam by permeation through the body surface or membrane, the composition comprising fenoldopam to be administered, at a therapeutically effective rate, in combination with a permeation enhancer or mixture. Also disclosed are drug delivery devices and methods for the transdermal administration of fenoldopam for the treatment of hypertension, congestive heart failure, and chronic and acute renal failure.

Abstract: Composition of matter for application to a body surface or membrane to administer pergolide by permeation through the body surface or membrane, the composition comprising pergolide to be administered, at a therapeutically effective rate, alone or in combination with a permeation enhancer or mixture. Also disclosed are drug delivery devices containing the pergolide or pergolide and enhancer composition and methods for the transdermal administration of the pergolide and pergolide/enhancer composition.

Abstract: A transdermal structure is provided for delivering cannabis chemical(s) to one's bloodstream. The structure comprises a backing layer which carries the cannabis chemical(s). The chemicals are contained in a film on the backing layer or within a cavity formed in the backing layer. Alternatively, an opening in a secondary layer that overlies the backing layer may be used to create the cavity. The structure is applied to one's skin so that the cannabis chemicals are in contact with the skin. A polymer material which is mixed with the cannabis and placed in the cavity or a membrane over the cavity may be used to control the flow of cannabis chemical (s) into the bloodstream. In an alternative embodiment, a porous material impregnated with cannabis chemical (s) may be used to hold the chemical(s) in the cavity.

Abstract: Rate controlled transdermal nicotine delivery systems are disclosed which utilize an in-line adhesive to maintain the systems on the skin. The initial equilibrated concentration of nicotine in the nicotine reservoir and the adhesive is below saturation, preferably at a thermodynamic activity no greater than 0.50, and the reservoir comprises the nicotine dissolved in a polymer with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of nicotine in the reservoir is sufficient to prevent the activity of the nicotine in the reservoir from decreasing by more than about 75% and preferably no more than about 25% during the predetermined period of administration; and the thicknesses of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and, preferably at least 75% initial equilibrated nicotine loading is in the reservoir layer.

Abstract: The present invention is directed to the transdermal administration of a drug together with a suitable amount of an acyl lactylate permeation enhancer. The invention includes a transdermal drug delivery device comprising a matrix adapted to be placed in drug- and- permeation enhancer-transmitting relation with a skin site. The matrix contains sufficient amounts of an acyl lactylate permeation enhancer and drug, in combination, to continuously administer drug to the systemic circulation of a patient at a therapeutically effective rate. The invention is also directed to compositions and methods for transdermal administration of a drug together with an acyl lactylate permeation enhancer, alone or in combination with other enhancers.

Abstract: Osmotically driven drug delivery devices with walls of porous hydrophobic material as the sole diffusion-limiting wall component are disclosed. Despite pores which are considerably larger than the molecular dimensions of osmotically active species in the interior of the device, despite pores which by their hydrophobic character do not permit the passage of liquid water, and despite the absence of a cellulosic semi-permeable membrane, the devices absorb water by osmosis without loss of the osmotically active species, and function in a manner analogous to osmotic pumps of the prior art. By permitting the use of hydrophobic substances as the wall material, the invention permits the device to be constructed entirely from biodegradable materials.

Abstract: A composition of matter for application to a body surface or membrane to administer a drug by permeation through the body surface or membrane, the composition comprising, in combination the drug to be administered, in a therapeutically effective amount; and a permeation enhancing mixture comprising a monoglyceride or a mixture of monoglycerides, and a lactic ester or a mixture of lactate esters, present in specific concentrations.

Abstract: A composition of matter for application to a body surface or membrane to coadminister an estrogen and progesterone by permeation through the body surface or membrane, the composition comprising, in combination, the estrogen and progesterone to be administered, in a therapeutically effective amount; and a permeation-enhancing mixture comprising a monoglyceride or a mixture of monoglycerides, and a lactate ester or a mixture of lactate esters at specific concentrations. The composition of matter is used to provide hormone replacement therapy to a woman.

Abstract: The present invention provides compositions and systems for the transdermal administration of a drug together with glycerol monolinoleate as a permeation enhancer. An example of a delivery system of the invention is a system (20) having a drug reservoir (22) containing together a drug to be delivered and glycerol monolinoleate permeation enhancer. Reservoir is sandwiched between a backing layer (24) and an in-line contact adhesive layer (28).

Abstract: A diffusional drug delivery device is described which can provide for stability of the adhesive and system components, elimination of the initial burst of drug and hence irritation, and to provide for delayed onset of therapeutic effect along with delivery of a therapeutic agent at an optimum rate. The therapeutic agent in a first form which is suitable for storage, and the anhydrous activating means are inert when in an anhydrous environment. Moisture activates the system whereby the activating means provides an acidic or basic solution and the first form of the therapeutic agent is converted to a second form which is suitable for absorption through the skin or mucosa.