Abstract: Systemic delivery of insulin to a mammalian host is accomplished by inhalation of a dry powder of insulin. It has been found that dry insulin powders are rapidly absorbed through the alveolar regions of the lungs.

Abstract: A device for accurately delivering aerosolized doses of a medicament disperses a measured amount of drug in a measured volume of carrier gas and transfers the resulting aerosol to a chamber prior to inhalation by a patient. The chamber is filled efficiently with the aerosol, and inhalation by the patient draws the aerosol dose into the lungs. This is followed by the inhalation of atmospheric air that will push the initial dose well into the lung interiors. The apparatus optimally includes a dose regulator, a counter, a clock, a dose memory and a signal to indicate when a dose is ready for inhalation. Optimal chamber designs are disclosed.

Abstract: A method for aerosolizing a powder utilizes a receptacle having a cavity containing a powder. An access end of an extraction tube is inserted into the cavity, and an inlet opening is formed in the receptacle. A pressurized gas is flowed through the inlet opening, through the cavity and through the extraction tube to move the powder in the cavity into the extraction tube where the powder is entrained in the gas to form an aerosol.

Abstract: According to the subject invention, dispersible dry powder pharmaceutical-based compositions are provided, including methods for their manufacture and dry powder dispersion devices. A dispersible dry powder pharmaceutical-based composition is one having a moisture content of less than about 10% by weight (%w) water, usually below about 5%w and preferably less than about 3%w; a particle size of about 1.0-5.0 &mgr;m mass median diameter (MMD), usually 1.0-4.0 &mgr;m MMD, and preferably 1.0-3.0 &mgr;m MMD; a delivered dose of about >30%, usually >40%, preferably >50%, and most preferred >60%; and an aerosol particle size distribution of about 1.0-5.0 &mgr;m mass median aerodynamic diameter (MMAD), usually 1.5-4.5 &mgr;m MMAD, and preferably 1.5-4.0 &mgr;m MMAD. Such compositions are of pharmaceutical grade purity.

Abstract: A method for forming at least one opening in a receptacle comprises the steps of providing a receptacle having a cover with an exterior surface and an interior surface covering a cavity. A cutting mechanism is also provided having at least one blade. The cover is pierced with the blade, and the blade is moved through the cover to cut a portion of the cover and create an opening in the cover to provide access into the cavity. Further, the cut portion curls on top of the exterior surface as the opening is created.

Abstract: The present invention is directed to methods and devices for delivering an active agent formulation to the lung of a human patient. The active agent formulation may be in dry powder form, it may be nebulized, or it may be in admixture with a propellant. The active agent formulation is delivered to a patient at an inspiratory flow rate of less than 17 liters per minute. The bioavailability of the active agent was found to increase at these flow rates when compared to inspiratory flow rates of 17 liters per minute or more.

Abstract: Stabilized dispersions are provided for the delivery of a bioactive agent to the respiratory tract of a patient. The dispersions preferably comprise a plurality of perforated microstructures dispersed in a suspension medium that typically comprises a hydrofluoroalkane propellant. As density variations between the suspended particles and suspension medium are minimized and attractive forces between microstructures are attenuated, the disclosed dispersions are particularly resistant to degradation, such as, by settling or flocculation. In particularly preferred embodiments, the stabilized dispersions may be administered to the lung of a patient using a metered dose inhaler.

Abstract: Compositions and methods are provided for the administration of particulates comprising at least one bioactive agent which, in selected embodiments, may comprise and immunoactive agent. In this respect, the invention provides for both topical and systemic delivery of the bioactive agent using, for example, the respiratory, gastrointestinal or urogenital tracts. The particulates may be in the form of dry powders or combined with a non-aqueous suspension medium to provide stabilized dispersions. In preferred embodiments, the disclosed compositions will be used in conjunction with inhalation devices such as metered dose inhalers, dry powder inhalers, atomizers or nebulizers for targeted delivery of the agent to mucosal surfaces.

Abstract: Systems and methods are provided for aerosolizing a pharmaceutical formulation. According to one method, respiratory gases are prevented from flowing to the lungs when attempting to inhale. Then, respiratory gases are abruptly permitted to flow to the lungs. The flow of respiratory gases may then be used to extract a pharmaceutical formulation from a receptacle and to place the pharmaceutical formulation within the flow of respiratory gases to form an aerosol.

Abstract: A process for preparing ultrafine powders of biological macromolecules comprises atomizing liquid solutions of the macromolecules, drying the droplets formed in the atomization step, and collecting the particles which result from drying. By properly controlling each of the atomization, drying, and collection steps, ultrafine dry powder compositions having characteristics particularly suitable for pulmonary delivery for therapeutic and other purposes may be prepared.

Abstract: A powdered, dispersible composition having stable dispersibility over time is provided. The composition exhibits a characteristic glass transition temperature (Tg) and a recommended storage temperature (Ts), wherein the difference between Tg and Ts is at least about 10° C. (i.e. Tg−Ts is greater than 10° C.). The composition comprises a mixture of a pharmaceutically-acceptable glassy matrix and at least one pharmacologically active material within the glassy matrix. It may be further mixed with a powdered, pharmaceutically-acceptable carrier. It is particularly valuable in unit dosage form having a moisture barrier, in combination with appropriate labelling instructions.

Abstract: Dispersibility of a respirable powder, administrable by inhalation, is increased by including a pharmaceutically acceptable water-soluble polypeptide.

Abstract: According to the subject invention, dispersible dry powder pharmaceutical-based compositions are provided, including methods for their manufacture and dry powder dispersion devices. A dispersible dry powder pharmaceutical-based composition is one having a moisture content of less than about 10% by weight (%w) water, usually below about 5%w and preferably less than about 3%w; a particle size of about 1.0-5.0 &mgr;m mass median diameter (MMD), usually 1.0-4.0 &mgr;m MMD, and preferably 1.0-3.0 &mgr;m MMD; a delivered dose of about >30%, usually >40%, preferably >50%, and most preferred >60%; and an aerosol particle size distribution of about 1.0-5.0 &mgr;m mass median aerodynamic diameter (MMAD), usually 1.5-4.5 &mgr;m MMAD, and preferably 1.5-4.0 MMAD. Such composition are of pharmaceutical grade purity.

Abstract: The invention provides methods, systems and apparatus for the metered transport of fine powders into receptacles. According to one exemplary method, the fine powder is first fluidized. At least a portion of the fluidized fine powder is then captured. The captured fine powder is then transferred to a receptacle, with the transferred powder being sufficiently uncompacted so that it may be dispersed upon removal from the receptacle.

Abstract: The invention provides a method for forming particles of a target substance (26), involving: (a) preparing a solution or suspension of the substance in a vehicle (21) which is or includes either a near-critical fluid (21) or a first supercritical fluid; (b) introducing the solution or suspension into a particle formation vessel (32); and (c) contacting the solution or suspension, in the particle formation vessel, with a second super-critical fluid, under conditions which allow the second supercritical fluid to cause precipitation of particles of the target substance from the solution or suspension; wherein the second supercritical fluid is miscible or substantially miscible with the vehicle and is a fluid in which the target substance is insoluble or substantially insoluble.

Abstract: Methods for preparing dry powders having hydrophobic and hydrophilic components comprise combining solutions of the components and spray drying them simultaneously in a spray dryer. The hydrophilic and hydrophobic component are separately dissolved in separate solvents and directed simultaneously through a nozzle, usually a coaxial nozzle, into the spray dryer. The method provides dry powders having relatively uniform characteristics.

Abstract: The invention relates to a process for the production of morphologically uniform microcapsules that contain peptides, proteins or other water-soluble biologically active substances as active ingredients as well as microcapsules that are produced according to this process with a degree of concentration of between 3 to 30% by weight and a diameter ≦8 &mgr;m. According to the invention, biodegradable polymers are dissolved in a halogen-free solvent or solvent mixture, and the buffered active ingredient solution, which has a pH of between 6.0 to 8.0, is dispersed into this solution. Then, an aqueous solution that contains a surfactant (W/O/W-emulsion) is added to this W/O-emulsion, and the solvent is removed. The microcapsules that are produced with this process do not show any tendency toward agglomeration. The encapsulation efficiency of the process is approximately 90 to 95%.

Abstract: The present invention provides highly dispersible spray-dried powder compositions, and in particular, inhaleable dry powder compositions for aerosolized delivery to the lungs. The powders of the invention are produced by spray drying a 4 &agr;-helix bundle protein under conditions which both (i) protect the protein from aggregation and (ii) provide particles suitable for inhalation (i.e., demonstrating superior aerosol performance).

Abstract: Spray drying methods for forming powder compositions for pharmaceutical applications are disclosed. According to one aspect of the invention, the spray drying feed stock comprises a bioactive agent, surfactant, and a blowing agent. Another aspect of the invention is directed to spray drying a feed stock comprising a phospholipid and calcium chloride.

Abstract: A material or mixture of materials which is not itself storage stable is rendered storage stable by incorporation into a water-soluble or swellable glassy or rubbery composition which can then be stored at ambient temperature. Recovery is by adding aqueous solution to the composition.