Abstract: The present invention describes the configuration of a porous sheet for improving the efficiency for generating an aerosol from a liquid formulation. This aerosolized liquid formulation can be used for intrapulmonary delivery of pharmaceutically active drugs and diagnostic agents when said invention is used in conjunction with the appropriate device. The individual pores in each array (defined as the rows and columns of pores for example in a rectangular array) are generated such that there is a discrete or continuous variation in the pore size within the plurality of pores on the sheet. The drug is subsequently aerosolized by forcing the liquid formulation through the pores on the sheet. The resulting aerosol will contain a controlled range of particle sizes defined by the properties of the porous sheet and the liquid formulation.

Abstract: The invention provides a method of rapidly machining multiple, often similar or nearly identical, features using a LASER machining system. During LASER machining, light of a wavelength and intensity that will modify the workpiece to be machined is directed at the workpiece and interacts to produce the desired change. If several features are to be machined, the processing speed can be increased by operating on a multiplicity of features at once. In one embodiment of the invention, this is achieved by separating the LASER beam into multiple beams and machining the desired features simultaneously.

Abstract: Aerosol dispensing devices and methods for using the same for administering aerosolized drugs to a subject are provided. Aspects of the aerosol dispensing device include an aerosol production unit configured to produce an aerosol from a liquid containing a pharmaceutically active drug, and a burst valve adapted to mechanically open in response to a subject's inhalation. The burst valve is configured to prevent airflow through the device until the subject's inhalation produces an operational pressure difference across the burst valve. In some embodiments, the operational pressure difference can be 15 cm H2O or less. Aspects of the invention can also include a heating element configured to evaporate water from aerosol droplets. The devices and methods of the invention find use in a variety of applications, such as in applications in which it is desired to administer an aerosolized drug to a subject.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient's breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: A drug delivery device containing a sterile multi dose reservoir. Said sterile reservoir can be used with many types of delivery including injectors or aerosol drug delivery systems. Elevated pressure surrounding the reservoir is used during storage to ensure sterility is maintained. Mechanisms to prevent delivery in the case of potential compromise of sterility are disclosed. A device using the pressure to meter formulation from the reservoir is disclosed.

Abstract: Dosages of inhaled insulin are controlled within a narrow range by controlling the total volume of air inhaled by a patient. By repeatedly delivering aerosolized insulin with the same total inhaled volume of air, the amount of insulin delivered to the patient each time is consistent. A device for delivering insulin by inhalation is disclosed which device comprises a means for measuring inhaled volume and for halting inhalation at a pre-determined point. The device also comprises an adjustable means for applying various amounts of force to a container of formulation to expel different amounts of drug from the container based on the force applied.

Abstract: A nozzle comprising a thin, flexible substantially planar polymeric film having a plurality of pores with structures allowing for generation of an aerosol at reduced extrusion pressure is disclosed. The pores can comprise at least two sections, or steps, in which the thickness of the membrane is reduced in stepwise fashion, or the pores can be tapered. Nozzles formed comprising pores having such structures permit aerosol generation at lower extrusion pressures, thereby allowing for decreased weight of aerosolization devices, increased efficiency, increased portability and increased battery life. The pore structures also allow for the use of thicker, more easily processed polymeric films in manufacturing while having a thinner, more efficient aerosolization area. The use of decreased extrusion pressures also results in increased uniformity in aerosol generation and improved reliability of other components.

Abstract: Method for fabricating and inspecting small holes in a material are disclosed. The method includes directing light onto the material and through the holes formed in the material, and then collecting the light passing through the holes in the material onto a detector. The methods further include analyzing the light for properties of the holes, and modifying the process based these detected properties.

Abstract: Methods are provided for increasing libido and/or treating erectile dysfunction in a man. The methods include the administration of a formulation testosterone alone, another fast-acting drug to treat erectile dysfunction or a combination of the testosterone and the other drug where at least one is delivered by aersolization. The formulation is preferably aerosolized and inhaled into a patient's lungs where particles of testosterone and/or the fast-acting erectile dysfunction drug deposits on lung tissue and then enter the patient's circulatory system.

Abstract: Methods and devices for delivering aerosolized formulations containing polynucleotides to specified regions within a subject's respiratory tract are disclosed. The methods find use in the delivery of ribozymes, antisense polynucleotides, and DNA and RNA expression vectors into airway epithelial cells, alveoli, pulmonary macrophages and other cells in the respiratory tract (including the oropharynx, nose, nasopharynx). These methods may be used for optimization of transfection efficiency and expression in vivo, and for in vivo expression, for example for generating an immune response, or inducing immunological tolerance.

Abstract: A method is provided for filling needleless injector capsules with liquid drug, which eliminates or reduces trapped air bubbles in the drug. A two-stage vacuum method is disclosed which enables the capsule to be evacuated rapidly to very low pressure prior to filling. The method is also suitable for filling other small containers with liquids.

Abstract: Method for fabricating and inspecting small holes in a material are disclosed. The method includes directing light onto the material and through the holes formed in the material, and then collecting the light passing through the holes in the material onto a detector. The methods further include analyzing the light for properties of the holes, and modifying the process based these detected properties.

Abstract: A portable air temperature controlling device useful for warming air surrounding an aerosolized drug formulation. Warming the air of an aerosol makes it possible to reduce the diameter of aerosol particles produced by an aerosol generation device. Additionally, warming the air forces the diameter of the aerosol particles to be in the range required for systemic drug delivery independent of ambient conditions. Smaller particles can be more precisely targeted to different areas of the respiratory tract.

Abstract: Dosages of inhaled insulin are controlled within a narrow range by controlling the total volume of air inhaled by a patient. By repeatedly delivering aerosolized insulin with the same total inhaled volume of air, the amount of insulin delivered to the patient each time is consistent. A device for delivering insulin by inhalation is disclosed which device comprises a means for measuring inhaled volume and for halting inhalation at a pre-determined point. The device also comprises an adjustable means for applying various amounts of force to a container of formulation to expel different amounts of drug from the container based on the force applied.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient's breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: A system is disclosed which makes it possible for a patient to be delivered gradually reduced amounts of nicotine over time thereby allowing the patient to be gradually weaned off of dependence on nicotine and quit smoking. The system is comprised of a means for aerosolizing a formulation and containers of formulation. The formulation is comprised of nicotine in a pharmaceutically acceptable carrier. Preferably, a plurality of containers are produced wherein the concentration of nicotine in the different containers or different groups of containers is reduced. The patient uses containers with the highest concentration initially and gradually moves towards using containers with lower and lower concentrations of nicotine until the patient's dependence on nicotine is eliminated.

Abstract: A nozzle comprising a thin, flexible substantially planar polymeric film having a plurality of pores with structures allowing for generation of an aerosol at reduced extrusion pressure is disclosed. The pores can comprise at least two sections, or steps, in which the thickness of the membrane is reduced in stepwise fashion, or the pores can be tapered. Nozzles formed comprising pores having such structures permit aerosol generation at lower extrusion pressures, thereby allowing for decreased weight of aerosolization devices, increased efficiency, increased portability and increased battery life. The pore structures also allow for the use of thicker, more easily processed polymeric films in manufacturing while having a thinner, more efficient aerosolization area. The use of decreased extrusion pressures also results in increased uniformity in aerosol generation and improved reliability of other components.

Abstract: A portable air temperature controlling device useful for warming air surrounding an aerosolized drug formulation is described. Warming the air of an aerosol makes it possible to reduce the size of aerosol particles produced by an aerosol generation device. Additionally, warming the air forces the size of the aerosol particles to be in the range required for systemic drug delivery independent of ambient conditions. Smaller particles can be more precisely targeted to different areas of the respiratory tract.

Abstract: A needle-less injector comprises a cartridge (3) prefilled with liquid ((9), which cartridge contains a free sliding piston (32) and an injection orifice (10). A ram (22) is urged by a pre-loaded spring (24) for striking the said piston to cause the injections. Adjusting means (6) can be provided to vary the volume injected. A trigger device (26, 30) initiates injection only when the optimum contact pressure is reached between the discharge orifice (1) and epidermis of the subject. The initial loading of the power spring (24) is sufficient to dispense all of the contents of the medicament cartridge in one dose or multiple sequential doses. Disposable and reusable embodiments are described.

Abstract: Stable aqueous formulations which are free of products derived from human or animal origin and which maintain high biological activity and high chemical and physical stability of alpha-type interferon for an extended period of time. Methods of producing stable aerosol formulations of the same for delivery to the lungs are also provided, as well as systems and methods of delivering the formulations to the lungs for systemic absorption.