Remarkably, with the exception of anaesthetic gases, the ancient human practice of inhaling substances into the lungs for systemic effect has only just begun to be adopted by modern medicine. Treatment of asthma by inhaled drugs began in earnest in the 1950s, and now such 'topical' or targeted treatment with inhaled drugs is considered for treating many other lung diseases. More recently, major advances have led to increasing interest in systemic delivery of drugs by inhalation. Small molecules can be delivered with very rapid action, low metabolism and high bioavailability; and macromolecules can be delivered without injections, as highlighted by the recent approval of the first inhaled insulin product. Here, we review these advances, and discuss aspects of lung physiology and formulation composition that influence the systemic delivery of inhaled therapeutics.

Inhaling medicines: delivering drugs to the body through the lungs

An electronic smoking article comprising an aerosol generator and a mechanical aerosol converter insert having the capacity to improve characteristics of aerosol produced by the aerosol generator, including sensory attributes.

Electronic smoking article

The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed.

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Nanomedicine in pulmonary delivery.

A dry powder medecine inhaler has an impeller (31) non-concentrically disposed in a mixing chamber (25). A motor spins the impeller at high speed. A plunger (106) introduces a dose of powdered medecine into the chamber so that all powder particles are available for intermixing disaggregation and comminution. An aperture (51) receives a first stream of air and passes it towards the mouthpiece for inhalation by the user. A wall (11) has at least one aperture (59) for diverting a portion of a main air stream into the aerosolizing chamber to mix with the particles to form a fine, low density, low velocity, dry mist of powdered medecine for inhalation by the user.

Dry powder inhaler

An electrically heated smoking system includes a shell and a replaceable mouthpiece. The shell includes an electric power supply and electric circuitry. The mouthpiece includes a liquid storage portion and a capillary wick having a first end and a second end. The first end of the wick extends into the liquid storage portion for contact with liquid therein. The mouthpiece also includes a heating element for heating the second end of the capillary wick, an air outlet, and an aerosol forming chamber between the second end of the capillary wick and the air outlet. When the shell and mouthpiece are engaged or connected, the heating element is in electrical connection with the power supply via the circuitry, and a flowpath for air is defined from at least one air inlet to the air outlet via the aerosol forming chamber. In use, liquid is transferred from the liquid storage portion towards the heating element by capillary action in the wick. Liquid at the second end of the capillary wick is vaporized by the heating element. The supersaturated vapor created, is mixed and carried in the air flow from the at least one air inlet to the aerosol forming chamber. In the aerosol forming chamber, the vapor condenses to form an aerosol, which is carried towards the air outlet.

Electrically heated smoking system having a liquid storage portion

A device for delivering a drug by inhalation is disclosed. The device includes a body defining an interior flow-through chamber having upstream and downstream chamber openings, and a drug supply unit contained within the chamber for producing, upon actuation, a heated drug vapor in a condensation region of the chamber. Gas drawn through the chamber region at a selected gas-flow rate is effective to form drug condensation particles from the drug vapor having a selected MMAD between 0.02 and 0.1 MMAD or between 1 and 3.5 gm. A gas-flow control valve disposed upstream of the unit functions to limit gas-flow rate through the condensation region to the selected gas-flow rate. An actuation switch in the device activates the drug-supply unit, such that the drug-supply unit can be controlled to produce vapor when the gas-flow rate through the chamber is at the selected flow rate.

Inhalation device for producing a drug aerosol

Devices and methods of entraining a substance within an airflow are disclosed. Condensation aerosol delivery devices and methods of consistently producing multiple doses of a substance, such as a drug, having high purity, high yield, characterized by a particle size distribution appropriate for pulmonary delivery, and which can be administered to a user in a single dose are also disclosed.

Multiple dose condensation aerosol devices and methods of forming condensation aerosols

The present invention provides novel condensation aerosols for the treatment of disease and/or intermittent or acute conditions. These condensation aerosols have little or no pyrolysis degradation products and are characterized by having an MMAD of between 1-3 microns. These aerosols are made by rapidly heating a substrate coated with a thin film of drug having a thickness of between 0.05 and 20 μm, while passing a gas over the film, to form particles of a desirable particle size for inhalation. Kits comprising a drug and a device for producing a condensation aerosol are also provided. The device contained in the kit typically, has an element for heating the drug which is coated as a film on the substrate and contains a therapeutically effective dose of a drug when the drug is administered in aerosol form, and an element allowing the vapor to cool to form an aerosol. Also disclosed, are methods for using these aerosols and kits.

Drug condensation aerosols and kits

The present invention relates to the inhalation delivery of aerosols containing small particles. Specifically, it relates to a method of forming an aerosol for use in inhalation therapy. In a method aspect of the present invention, a method of forming an aerosol for use in inhalation therapy is provided. The method involves the following steps: (a) heating a substrate coated with a composition comprising a drug at a rate greater than 1000 °C/s, thereby forming an vapor; and, (b) allowing the vapor to cool, thereby forming an aerosol, which is used in inhalation therapy. In another method aspect of the present invention, a method of forming an aerosol for use in inhalation therapy is provided. The method involves the following steps: (a) heating a substrate coated with a composition comprising a drug to form a vapor, wherein the coated composition is in the form of a film less than 10 µ thick; and, (b) allowing the vapor to cool, thereby forming an aerosol, which is used in inhalation therapy. In another method aspect of the present invention, a method of forming an aerosol for use in inhalation therapy is provided. The method involves the following steps: (a) heating a substrate coated with a composition comprising a drug to form a vapor in less than 100 milliseconds, wherein the vapor has a mass greater than 0.1 mg; and, (b) allowing the vapor to cool, thereby forming an aerosol, which is used in inhalation therapy.

Method of forming an aerosol for inhalation delivery

Smoking involves heating a drug to form a mixture of drug vapor and gaseous degradation products. These gases subsequently cool and condense into aerosol particles that are inhaled. Here, we demonstrate rapid and reliable systemic delivery of pure pharmaceutical compounds without degradation products through a related process that also involves inhalation of thermally generated aerosol. Drug is coated as a thin film on a metallic substrate and vaporized by heating the metal. The thin nature of the drug coating minimizes the length of time during which the drug is exposed to elevated temperatures, thereby preventing its thermal decomposition. The vaporized, gas-phase drug rapidly condenses and coagulates into micrometer-sized aerosol particles. For the commonly prescribed antimigraine drug rizatriptan, inhalation of these particles results in nearly instantaneous systemic drug action.

https://jpet.aspetjournals.org/content/jpet/early/2004/01/29/jpet.103.062893.full.pdf

Daniel J. Myers

Papers

Inhalation device for producing a drug aerosol

Multiple dose condensation aerosol devices and methods of forming condensation aerosols

Drug condensation aerosols and kits

Method of forming an aerosol for inhalation delivery

Fast Onset Medications through Thermally Generated Aerosols