Abstract: A method of inducing immune tolerance to a drug which is normally sensitizing to humans when applied to human skin or mucosa is provided. The sensitizing drug is continuously and co-extensively administered to a selected skin or mucosa site with the corticosteroid. Preferably, the corticosteroid is hydrocortisone or an ester thereof. The corticosteroid is administered to the selected skin or mucosa site at a rate and for a period of time sufficient to induce tolerance to the drug. Thereafter, the drug can be administered to the human, without administering any corticosteroid, without danger of inducing sensitization to the drug in the human.

Abstract: An iontophoretic agent delivery device having donor and counter electrodes comprised of either metal or a hydrophobic polymer loaded with a conductive filler is provided. The agent reservoir in the donor electrode assembly contains about 10 to 60 wt % hydrophobic polymer, about 10 to 60 wt % hydrophilic polymer, and up to 50% agent. Similarly, the electrolyte reservoir contains about 10 to 60 wt % hydrophobic polymer, about 10 to 60 wt % hydrophilic polymer, and up to 50% electrolyte. The agent reservoir, the electrolyte reservoir and the electrodes are preferably in the form of films which are laminated to one another. The hydrophobic polymer component in the agent/electrolyte reservoir prevents the reservoir from delaminating from the metal/hydrophobic polymer based electrode, even after hydration of the reservoirs.

Abstract: A membrane capable of inhibiting agent release from a delivery system when no electrical current is flowing and yet provide minimal impedance to electrically-assisted agent delivery, useful both for incorporating into electrotransport agent delivery systems and for use in measuring agent release rates in in vitro testing.

Abstract: A method of preventing sensitization in transdermal drug delivery by the inclusion of a corticosteroid, which will be co-extensively coadministered with the sensitizing agent.

Abstract: A method of inducing immune tolerance to a drug which is normally sensitizing to humans when applied to human skin or mucosa is provided. The sensitizing drug is continuously and co-extensively administered to a selected skin or mucosa site with the corticosteroid. Preferably, the corticosteroid is hydrocortisone or an ester thereof. The corticosteroid is administered to the selected skin or mucosa site at a rate and for a period of time sufficient to induce tolerance to the drug. Thereafter, the drug can be administered to the human, without administering any corticosteroid, without danger of inducing sensitization to the drug in the human.

Abstract: A drug formulation chamber for an intravenous administration set is provided. The intravenous administration set includes a container of an IV fluid, a drip chamber, a drug formulation chamber, and an adapter-needle assembly. The drug formulation chamber has a fluid inlet and a fluid outlet for maintaining a flow of IV fluid through the chamber. A portion of the chamber wall is comprised of a window material which allows the drug to diffuse therethrough but which prevents convective loss of the IV fluid. A flow distributor is provided within the chamber for distributing the flow of IV fluid along the interior surface of the window. A transdermal-type drug delivery device is adhered to the exterior surface of the window. Drug is delivered by the delivery device through the window and into the flowing IV fluid. The device delivers drug into the IV fluid at a rate that is independent of the flow rate of IV fluid through the formulation chamber.

Abstract: An implantable osmotically driven syringe is disclosed which can be used to deliver a beneficial agent, such as a drug, at a predetermined rate over an extended period of time. A movable piston divides the syringe into a beneficial agent-containing compartment and a driving compartment. The piston is movable into a position wherein the driving compartment has a volume of essentially zero. The syringe is driven by an osmotic engine which has a shaped wall surrounding, and in contact with, an osmotic solute. The wall is comprised of a semipermeable and/or microporous material which is permeable to the external fluid (e.g., water) but is impermeable to the solute. The engine also has a passageway forming a fluid flow path between the osmotic solute and the driving compartment. A portion of the wall is exposed to a fluid-containing external environment. At least about 30% of the wall which contacts the solute also is exposed to the fluid in the external environment.

Abstract: An osmotic device for delivering a beneficial drug, such as an anti-fungal, into the mouth of a human patient is disclosed. The device has a size and shape adapting it to be comfortably retained in the mouth for extended periods of time. The device comprises a wall surrounding a compartment housing a layer of an agent that is insoluble to very soluble in aqueous biological fluid, e.g., saliva, and a layer of a fluid swellable, hydrophilic polymer. A passageway in the wall connects the agent with the exterior of the device. The wall is permeable to the passage of aqueous biological fluid but substantially impermeable to the passage of the hydrophilic polymer. In one embodiment the beneficial agent has a different color than the hydrophilic polymer. The wall is sufficiently translucent to permit the patient to see the amount of drug/beneficial agent remaining to be delivered.

Abstract: A method of preventing sensitization in transdermal drug delivery by the inclusion of a corticosteroid, which wll be co-extensively coadministered with the sensitizing agent.

Abstract: A drug formulation chamber for an intravenous administration set is provided. The intravenous administration set includes a container of an IV fluid, a drip chamber, a drug formulation chamber, and an adapter-needle assembly. The drug formulation chamber has a fluid inlet and a fluid outlet for maintaining a flow of IV fluid through the chamber. A portion of the chamber wall is comprised of a material which is permeable to the drug but which prevents convective loss of the IV fluid. A transdermal-type drug delivery device is adhered to the semipermeable/microporous wall portion. Drug is delivered by the delivery device through the wall portion and into the flowing IV fluid. The device delivers drug into the IV fluid at a rate that is independent of the flow rate of IV fluid through the formulation chamber. The rate of drug delivery from the device into the IV fluid is controlled by either the wall portion or a membrane layer in the drug delivery device.

Abstract: An osmotically driven pump is provided that is capable of being miniaturized to a size suited for swallowing or implanting in an animal. The pump may be used to administer a drug in fluid form after an initial activation period during which substantially no drug is administered. The basic components of the pump are a shaped semipermeable membrane that encapsulates an osmotically effective solute and preferably a drug or other beneficial agent and a discharge port through which the drug or other beneficial agent is dispensed. A semipermeable or microporous outer cover surrounds the semipermeable membrane and seals it from an external aqueous environment. A water-swellable composition is operatively positioned between the end of the semipermeable membrane and the outer cover. Preferably, a water wicking layer at least partially surrounds the semipermeable membrane and is also sealed within the outer cover. In operation, the pump is placed in an aqueous environment.

Abstract: A drug formulation chamber for an intravenous administration set is provided. The intravenous administration set includes a container of an IV fluid, a drip chamber, a drug formulation chamber, and an adapter-needle assembly. The drug formulation chamber houses a diffusional or an osmotically driven drug delivery device. The osmotically driven delivery device has a semipermeable, microporous or diffusional wall which surrounds a compartment containing the drug. Drug is delivered through an orifice in the semipermeable/microporous wall or through the diffusional wall itself, into the IV fluid. The device delivers drug into the IV fluid at a rate that is independent of the flow rate of IV fluid through the formulation chamber. The rate of drug delivery is controlled by variably adjusting the surface area of the semipermeable/microporous/diffusional wall that is exposed to the IV fluid flowing through the drug formulation chamber.

Abstract: An improved osmotic engine is disclosed. The osmotic engine is adapted to be used with an osmotically driven syringe which can be used to deliver a beneficial agent, such as a drug, at a pre-determined rate over an extended period of time. The osmotic engine has an exterior wall defining a compartment which contains an osmotic solute. The wall comprises a thin permeable and/or microporous material which is permeable to an external fluid such as water but is impermeable to the solute. The wall also has a delivery orifice drilled therethrough. A rigid non-dissolving ring-shaped wall support is provided for maintaining the shape of the engine during use. The wall support also provides a fluid flow path extending from the semipermeable wall portion toward the delivery orifice.

Abstract: An agent dispenser of the fluid imbibing type having a flexible bag within a membrane and in which a wicking or wetting device is in contact with the outer surface of the membrane to keep such outer surface wet at all times for all attitudes of a containment vessel housing the bag and the membrane. The wicking device is in the form of a fabric tube, such as a stretch knit fabric, or a preformed hydrophilic polymeric sleeve, which can be mounted on the outer surface of the membrane and remain in contact with it so long as there is any liquid in the containment vessel. Since the amount of water drawn by the wicking device is controlled by the membrane porosity and the amount of a solute composition in an intermediate layer between the bag and the membrane, the wicking device provides for a continuous controlled delivery of agent from the inner bag of the dispenser.

Abstract: An improved imbibing agent dispenser having a snap-on closure which is highly reliable, is simple to assemble on one end of the agent dispenser, and can be made at minimum expense without requiring heat or an adhesive to bond the closure to the dispenser. The closure is held in place on the dispenser by a locking feature formed by a shoulder on the end of the dispenser and a ledge on an outer, annular wall of the closure, the ledge being removably hooked beneath and biased toward the shoulder to releasably lock the closure to the dispenser. An important aspect of this closure is that the design provides for the complete containment of a solute component within the dispenser.

Abstract: A transdermal therapeutic system which utilizes electrical current to facilitate agent delivery and which isolates the electrochemical reactants and products from the agent containing reservoir.

Abstract: An agent dispenser of the fluid imbibing type wherein the dispenser has a closure, such as a plug, closing an open end of the dispenser. The closure has a catheter coupled with it, and the catheter is in agent communication with the interior of the agent receiving means of the dispenser when the closure is put into place in closing relationship to the dispenser. Thus, when the agent receiving portion (reservoir) of the agent receiving means is filled, such as by a needle passing through a septum at the outer end of the closure, not only will the reservoir be filled, but also the catheter will be filled and thereby be primed, so that the catheter will be ready for use after it has been completely primed. The present invention, therefore, permits the filling of the reservoir and the priming of the catheter in a single step.

Abstract: Applications of bioerodible polymers as surgical "leave behind" products in the areas of orthopedic, thoracic, abdominal, ocular and liver/spleen surgery.

Abstract: Rate-controlled transdermal delivery devices are disclosed which utilize an in-line adhesive to maintain the device on the skin and deliver an agent which is a solvent for the in-line adhesive. The initial equilibrated concentration of the agent in the agent reservoir and the adhesive is below saturation and the reservoir comprises the agent dissolved in a solvent with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of the agent in reservoir is sufficient to prevent the activity of the agent in the reservoir from decreasing by more than about 50% and preferrably 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, preferrably at least 75% initial equilibrated agent loading is in the reservoir layer.

Abstract: A transdermal delivery device for delivering drugs, typically ionized drugs, from an aqueous reservoir is described. The device comprises an aqueous drug reservoir in the form of a gel confined between an impermeable backing member and a porous support structure. In preferred embodiments the support structure is the substrate to which is applied a porous or patterned in-line adhesive. A strippable release liner is preferably provided on the adhesive while in the package. The devices are usable to deliver drugs such as chlorpheniramine maelate, brompheneiramine maleate and scopolamine hydrobromide.