Dry powder drug delivery formulations, methods of use, and devices therefore

• US 8,597,616 B2
• Filed: 10/22/2008
• Issued: 12/03/2013
• Est. Priority Date: 10/22/2007
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Kraft, Edward R., Hoskins, Stephen L., Enkhbaatar, Perenlei, Traber, Daniel L.
• Primary Examiner(s): Pagonakis, Anna
• Assistant Examiner(s): West, Theodore R
• Application Number:
  US12/256,438
• Publication Number:
  US 20120111324A1
• Time in Patent Office: 1,868 Days
• Field of Search: None
• US Class Current: 424/46
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/08 Bronchodilators

Abstract

The present disclosure relates to systems, methods, and formulations for the pulmonary administration of one or more therapeutic agents, in dry powder form, in a single, large dose quantity. These formulations, methods, and systems are useful in the treatment of patients suffering from toxic or harmful gas exposure, such as nerve gas exposure, as well as in the treatment of patients suffering from diseases of the pulmonary system, including tuberculosis, cystic fibrosis, and chronic obstructive pulmonary disease (COPD).

Claims

1. A single unit dosage form for pulmonary delivery of an adrenergic agonist, comprising a single unit dosage receptacle containing a single delivery dosage amount of at least 20 mg of the adrenergic agonist as an essentially solvent free powder milled to an average particle size of less than about 10 μ

m, and a pharmaceutically acceptable single dose quantity of a non-CFC haloalkane propellant.

2. The single unit dosage form of claim 1, wherein the haloalkane propellant is 1,1,2,2-tetrafluroethane (R-134a).

3. The single unit dosage form of claim 1, wherein the adrenergic agonist is selected from the group consisting of epinephrine, norepinephrine, α

-methylnorepinephrine, isoproterenol, albuterol, isoetharine, metaproterenol, terbutaline, pseudoephedrine, phenylephrine, and ephedrine, epinephrine analogs, and pharmaceutically acceptable salts, solvates, hydrates, prodrugs, and polymorphs thereof.

4. The single unit dosage form of claim 1, wherein the at least one adrenergic agonist is milled to an average particle size of less than about 5 μ

m.

5. The single unit dosage form of claim 1, wherein the single unit dosage receptacle further comprises one or more additional therapeutic agents selected from the group consisting of nerve-agent therapeutic agents, steroids, anticholinesterases, antioxidants, β

₂ agonists, anti-inflammatories, NSAIDs, bacterial protein synthesis inhibitors, interferons, oxazolidinones, epinephrine, combinations thereof, as well as pharmaceutically-acceptable salts, prodrugs, polymorphs, and solvates thereof.

6. The single unit dosage form for pulmonary delivery of claim 1, wherein the adrenergic agonist is selected from the group consisting of epinephrine, norepinephrine, α

-methylnorepinephrine, isoproterenol, albuterol, aminophylline, beclomethasone, dyphylline, flunisolide, isoetharine, metaproterenol, oxtriphylline, terbutaline, theophylline, pseudoephedrine, phenylephrine, and ephedrine, alone or in combination, as well as the pharmaceutically-acceptable salts, solvates, hydrates, prodrugs, and polymorphs thereof.

7. A method for aerosolizing a bioactive adrenergic agonist composition, the method comprising:

providing an aerosol delivery system that comprises at least two separate chambers separated by a valve, one propellant chamber comprising a pharmaceutically acceptable single dose quantity of propellant and a second active agent chamber comprising an essentially solvent free dry powder drug composition that includes an adrenergic agonist, wherein the system is adapted and dimensioned to admix and deliver at least 20 mg of the adrenergic agonist in one emergency treatment when the valve separating the chambers is opened and the propellant mixes with the drug composition and forms an aerosol for inhalation by a patient upon release from the system.

8. The method of claim 7, wherein the the active agent chamber further comprises one or more additional therapeutic agents selected from the group consisting of nerve-agent therapeutic agents, steroids, anticholinesterases, antioxidants, β

₂ agonists, anti-inflammatories, NSAIDs, bacterial protein synthesis inhibitors, interferons, oxazolidinones, epinephrine, combinations thereof, as well as pharmaceutically-acceptable salts, prodrugs, polymorphs, and solvates thereof.

9. The method of claim 7, wherein the essentially solvent free dry powder drug composition consists essentially of epinephrine or a salt thereof in a dosage amount of at least 20 mg.

10. The method of claim 7, wherein the adrenergic agonist is selected from the group consisting of epinephrine, norepinephrine, α

-methylnorepinephrine, isoproterenol, albuterol, aminophylline, beclomethasone, dyphylline, flunisolide, isoetharine, metaproterenol, oxtriphylline, terbutaline, theophylline, pseudoephedrine, phenylephrine, and ephedrine, alone or in combination, as well as the pharmaceutically-acceptable salts, solvates, hydrates, prodrugs, and polymorphs thereof.