Abstract: A method for producing a nozzle useful in generating a fine aerosol for delivery of therapeutic or diagnostic agents is provided. The method comprises focusing a laser source onto a thin, preferably flexible material so as to form pores substantially through the material. The pores are formed to have an unflexed exit aperture diameter in the range of about 0.5 to about 25 microns, depending on the size of the aerosol particles desired for a particular application. The nozzle may have a variety of shapes and be distributed in a variety of patterns. An elevated area can be formed around the exit aperture of the nozzle in order to prevent intrusion of liquid into the nozzle.

Abstract: A nozzle comprised of a thin, flexible membrane material having a plurality of pores is disclosed. In one embodiment, the pores have an unflexed exit aperture diameter in the range of about 0.5 to about 2 microns (preferably about 1 micron) and are positioned substantially uniformly in the material, preferably about 50 microns apart. The nozzle preferably has a conical or trumpet-shaped cross-section. In another aspect of the invention, the exit aperture of the nozzle is surrounded by an elevated area protruding above the substantially planar exit side of the membrane in order to prevent intrusion of liquid back into the nozzle. The nozzle can be used to form an aerosol containing a pharmaceutical composition from the exit side of the nozzle upon forcible application of the composition to the entrance side of the nozzle. This aerosol can be used to administer the pharmaceutical composition, for example, to the eye or to a selected portion of the respiratory tract.

Abstract: The present invention relates to the use of calcium ion and/or sugars to minimize thermal aggregation of DNase and to the use of calcium ion to stabilize liquid solutions of DNase, the solutions having a pH of less than neutral. DNase is the active pharmaceutical principle and the solutions may contain other pharmaceutically acceptable excipients making them suitable for pharmaceutical administration. In the first instance, calcium ion/sugar minimizes the effects of thermal aggregation in the solution. In the second aspect, calcium ion stabilizes the lower pH solutions from protein precipitation.

Abstract: Formulations are disclosed as are aerosols created therefrom. The formulations are comprised of (a) a pharmaceutically active drug which does not ionize in solution; (b) an electrolyte; and (c) a solvent which is preferably water and/or ethanol. The electrolyte reduces electrostatic charging on particles of aerosol formed thereby enhancing characteristics of the aerosol particles which are important for efficient, repeatable intrapulmonary drug delivery.

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: Pegylation or glycosylation of therapeutic proteins to enhance at least one of the solubility, stability and bioavailability thereof, for delivery of an effective amount in an aerosol delivery to the lungs using a minimal number of puffs.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by a method whereby an aerosolized insulin formulation is delivered to a patient's lungs and the rate at which the insulin is absorbed into the blood is increased by the use of an inhale-exhale breathing maneuver. Particles of insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by instructing the patient to inhale maximally and thereafter exhale maximally. This maneuver causes a spike in the rate at which insulin enters the circulatory system thereby increasing the rate at which glucose is removed from the circulatory system. The 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 for generating aerosol is disclosed, which system comprises a multiple-dose container, a device which provides the means for aerosol generation and delivery of an aerosol and a disposable package comprised of a single-dose container with a means for drug intake and which can be loaded into the device and filled with drug from the multiple-dose container, and an aerosol generating nozzle material. In one embodiment, the single-dose container of the disposable package comprises a needle which is used to penetrate a self-sealing, re-sealable area on a multiple-dose container holding drug under positive pressure. The drug leaves the multiple-dose container and enters the single-dose container via an open channel in the needle while preserving the sterility of the liquid in the multiple dose container.

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: Formulations are disclosed as are aerosols created therefrom. The formulations are comprised of (a) a pharmaceutically active drug which does not ionize in solution; (b) an electrolyte; and (c) a solvent which is preferably water and/or ethanol. The electrolyte reduces electrostatic charging on particles of aerosol formed thereby enhancing characteristics of the aerosol particles which are important for efficient, repeatable intrapulmonary drug delivery. A method is disclosed whereby molar amounts of charged molecules are adjusted so as to reduce electrostatic charge on aerosolized particles created from the formulation whereby the particles are less inclined to be drawn against surfaces of a patient's upper respiratory tract.

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: 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: Formulations are disclosed as are aerosols created therefrom. The formulations are comprised of (a) a pharmaceutically active drug which does not ionize in solution; (b) an electrolyte; and (c) a solvent which is preferably water and/or ethanol. The electrolyte reduces electrostatic charging on particles of aerosol formed thereby enhancing characteristics of the aerosol particles which are important for efficient, repeatable intrapulmonary drug delivery.

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: The need for the delivery of insulin by injection can be reduced or eliminated by a method whereby an aerosolized insulin formulation is delivered to a patient's lungs and the rate at which the insulin is absorbed into the blood is increased by the use of an inhale-exhale breathing maneuver. Particles of insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by instructing the patient to inhale maximally and thereafter exhale maximally. This maneuver causes a spike in the rate at which insulin enters the circulatory system thereby increasing the rate at which glucose is removed from the circulatory system. The insulinmay 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: Aerosolizable formulations are disclosed comprised of a pharmaceutically acceptable carrier, a pharmaceutically active drug or detectably labeled compound and a compound which is recognized by its distinct color, taste and/or smell even when present in a small amount and a low concentration. Examples of such compounds include menthol, peppermint, cinnamon and vanilla flavors and water soluble dyes. The compounds can be designed so that they are only detectable by a specific area of the tongue or seen under a certain wavelength of light. The degree of detection of the color, taste or smell of the compound is an indication of the degree of success in the delivery of an aerosolized formulation to a patient. The formulation is preferably delivered from a device which monitors and records information relating to the patient's respiratory movement and also scans and analyzes the aerosol prior to inhalation.

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: The present invention relates to the use of calcium ion and/or sugars to minimize thermal aggregation of DNase and to the use of calcium ion to stabilize liquid solutions of DNase, the solutions having a pH of less than neutral. DNase is the active pharmaceutical principle and the solutions may contain other pharmaceutically acceptable excipients making them suitable for pharmaceutical administration. In the first instance, calcium ion/sugar minimizes the effects of thermal aggregation in the solution. In the second aspect, calcium ion stabilizes the lower pH solutions from protein precipitation.

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.