Alza Corporation

Other

James L Osborne

David J Enscore

Su Il Yum

Melinda K Nelson

Robert M Gale

Patricia S Campbell

Melinda K Smart

James B Eckenhoff

Jeremy C Wright

Sonya Merrill

David L Rivera

James A Hunt

Patrick S Wong

Nathan Roth

Randall G Berggren

Susan M Marks

Wouter E Roorda

John T Dunn

Karly S Wang

Donna D Causey

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.

Subsaturated nicotine transdermal therapeutic system

The present invention is directed to a material which can be used to deliver a drug, such as an antibiotic, into a diseased tissue pocket, such as a periodontal pocket. The material is preferably a bioerodible oligomer or polymer. The oligomer or polymer containing the drug is heated and is then delivered, preferably by injection, into the tissue pocket at a physiologically compatible elevated temperature. Once the bioerodible material is injected into the pocket, the material cools to the body temperature of the pocket. As it cools, the material hardens and remains in place in the tissue pocket. The hardened material bioerodes in the pocket and releases the drug over a period of several days.

Injectable drug delivery system and method

The present invention relates to an improvement in an osmotic delivery device wherein the device comprises a semipermeable wall comprising cellulose acetate butyrate and surrounding an internal compartment containing a beneficial agent or medicament formulation, a fluid-activated expandable driving member, optionally a partition layer between the agent formulation and the driving member, and, optionally a density member, and exit means in the semipermeable wall; and wherein the improvement comprises the cellulose acetate butyrate component of the semipermeable wall having a differential scanning calorimetry ('DSC') profile wherein the main or primary DSC peak has a minimum temperature peak above 228.degree. C. and the secondary DSC peak area is equal to or less than about 30% of the total combined areas of the primary and secondary DSC peaks. The invention also relates to the improved semipermeable membrane produced from cellulose acetate butyrate having a differential scanning calorimetry ('DSC') profile wherein the main DSC peak is at a temperature above 228.degree. C. and the secondary DSC peak area is equal to or less than about 30% of the total combined area of the primary and secondary DSC peaks, the semipermeable membrane providing a substantially improved uniform rapid startup performance for osmotic delivery devices.

Osmotic membrane and delivery device

A method of administering nicotine transdermally in which a nicotine patch, capable of administering nicotine for at least 16 hours at rates that are efficacious in smoking cessation therapy, is applied in the morning upon waking and removed prior to sleep. This method is effective even though nicotine is not essential during sleep and many smokers experience morning craving.

Method of administering nicotine transdermally

An in-line adhesive, useful for transdermal delivery devices comprising a mixture of high and low molecular weighted polyisobutylene having a ratio HMW PIB:LMW PIB in the range of about 5-40:95-60 which is substantially free of plasticizers and tackifiers is disclosed. The adhesive finds particular use as a component of a transdermal delivery device for delivering oily non-polar agents such as nicotine, benztropine, secoverine, dexsecoverine, and arecoline.

Polyisobutylene adhesives for transdermal devices

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 or a plasticizer 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 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 agent loading is in the reservoir layer. The devices are usable to deliver agents which are liquid at body temperatures such as benztropine, secoverine, nicotine, arecoline, polyethylene glycol monolaurate, glycerol monolaurate, glycerol monooleate and ethanol, for example.

Subsaturated transdermal therapeutic system having improved release

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 material 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 thickness of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and, preferably at least 75% of the initial equilibrated nicotine loading is in the reservoir layer.

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 or a plasticizer 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 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 agent loading is in the reservoir layer. The devices are usable to deliver agents which are liquid at body temperatures such as benztropine, secoverine, nicotine, arecoline, polyethylene glycol monolaurate, glycerol monolaurate, glycerol monooleate and ethanol, for example.

The invention herein pertains to methods and materials for producing a nicotine maintenance pouch. Laminates comprising a nicotine barrier layer and a nicotine degradation agent barrier layer are disclosed. In a preferred embodiment, the nicotine barrier layer comprises a nitrile rubber modified acrylonitrilemethyl acrylate copolymer. An especially preferred nicotine barrier material comprises, by weight percent, 75% acrylonitrile, and 25% methyl acrylate with 10% butadiene (AN-MA/B). The nicotine degradation agent barrier layer is preferably aluminum foil. In an especially preferred embodiment, the laminate comprises a layer of AN-MA/B adhered to a layer of aluminum foil, which in turn is adhered to a layer of paper stock. Pouches comprising a self-sealed nicotine barrier layer and a nicotine degradation agent barrier layer are disclosed. These pouches are preferably formed from the laminates above. A method for production of pouches comprises: (a) providing a laminate including a self-sealable nicotine barrier layer and a nicotine degradation agent barrier layer; and (b) sealing the self-sealable nicotine barrier layer to enclose a nicotine device.

Nicotine packaging materials

The invention herein pertains to methods and materials for producing a nicotine maintenance pouch. Laminates comprising a nicotine barrier layer and a nicotine degradation agent barrier layer are disclosed. In a preferred embodiment, the nicotine barrier layer comprises a nitrile rubber modified acrylonitrile-methyl acrylate copolymer. An especially preferred nicotine barrier material comprises, by weight percent, 75% acrylonitrile, and 25% methyl acrylate with 10% butadiene (AN-MA/B). The nicotine degradation agent barrier layer is preferably aluminum foil. In an especially preferred embodiment, the laminate comprises a layer of AN-MA/B adhered to a layer of aluminum foil, which in turn is adhered to a layer of paper stock. Pouches comprising a self-sealed nicotine barrier layer and a nicotine degradation agent barrier layer are disclosed. These pouches are preferably formed from the laminates above. A method for production of pouches comprising: (a) providing a laminate including a self-sealable nicotine barrier layer and a nicotine degradation agent barrier layer; and (b) sealing the self-sealable nicotine barrier layer to enclose a nicotine device.

Growing community of inventors

Mountain View, CA, United States of America

James L Osborne