Respiratory dispersion for metered dose inhalers comprising perforated microstructures

• US 8,246,934 B2
• Filed: 09/03/2010
• Issued: 08/21/2012
• Est. Priority Date: 09/29/1997
• Status: Expired due to Fees

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Weers, Jeffry G., Schutt, Ernest G., Dellamary, Luis A., Tarara, Thomas E., Kabalnov, Alexey
• Primary Examiner(s): ALSTRUM ACEVEDO, JAMES HENRY
• Application Number:
  US12/875,966
• Publication Number:
  US 20100329984A1
• Time in Patent Office: 718 Days
• Field of Search: 424/45, 424/46, 424/489
• US Class Current: 424/46
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• 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: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 11/10 Expectorants
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 11/16 Central respiratory analeptics
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: Y10S 977/904 : for medical, immunological, body treatment, or diagnosis
• CPC Class Codes: Y10S 977/906 : Drug delivery
• CPC Class Codes: Y10S 977/926 : Topical chemical, e.g. cosmetic or sunscreen

Abstract

A respiratory dispersion for pulmonary delivery comprises one or more bioactive agents, a suspension medium, and a plurality of perforated microstructures having a mean aerodynamic diameter of less than 5 μm. The suspension medium comprises at least one propellant and permeates the perforated microstructures.

Claims

1. A respiratory dispersion for pulmonary delivery, the respiratory dispersion comprising:

one or more bioactive agents;

a suspension medium;

a plurality of perforated microstructures having a mean aerodynamic diameter of less than 5 μ

m,

wherein said suspension medium comprises at least one propellant and permeates said perforated microstructures.

2. The respiratory dispersion of claim 1, wherein said propellant is selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane, perfluoroethane, monochlorodifluoromethane, 1,1-difluoroethane and combinations thereof.

3. The respiratory dispersion of claim 1 wherein said perforated microstructures comprise a surfactant.

4. The respiratory dispersion of claim 3 wherein said surfactant is selected from the group consisting of phospholipids, nonionic detergents, nonionic block copolymers, ionic surfactants, biocompatible fluorinated surfactants and combinations thereof.

5. The respiratory dispersion of claim 3 wherein said surfactant comprises a phospholipid.

6. The respiratory dispersion of claim 5 wherein said phospholipid is selected from the group consisting of dilauroylphosphatidylcholine, dioleylphosphatidylcholine, dipalmitoylphosphatidylcholine, disteroylphosphatidyl-choline behenoylphosphatidylcholine, arachidoylphosphatidylcholine and combinations thereof.

7. The respiratory dispersion of claim 1 wherein the mean geometric diameter of the perforated microstructures is between 1 and 5 μ

m.

8. The respiratory dispersion of claim 1 wherein said bioactive agent is selected from the group consisting of antiallergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, antiinfectives, leukotriene inhibitors or antagonists, antihistamine, antiinflammatories, antineoplastics, antocholinergics, anesthetics, anti-tuberculars, imaging agents, cardiovascular agents, enzymes, steroids, genetic material, viral vectors, antisense agents, proteins, peptides, and combinations thereof.

9. A respiratory dispersion of claim 1 wherein the bioactive agent comprises a bronchodilator.

10. A respiratory dispersion of claim 9 wherein said bronchodilator is selected from ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, albuterol, salmeterol, and terbutaline.

11. A respiratory dispersion of claim 1 wherein the bioactive agent comprises an anti-inflammatory agent.

12. A respiratory dispersion of claim 11 wherein the anti-inflammatory agent comprises an anti-inflammatory steroid.

13. A respiratory dispersion of claim 12 wherein the anti-inflammatory agent comprises one or more of fluticasone, beclomethasone, flunisolide, budesonide, tripedane, cortisone, prednisone, prednisolone, dexamethoasone, betamethasone or triamcinalone.

14. A respiratory dispersion of claim 1 comprising beclomethasone.

15. A respiratory dispersion of claim 1 comprising formoterol.

16. A respiratory dispersion of claim 1 comprising beclomethasone diproprionate and formoterol.

17. A respiratory dispersion of claim 1 wherein the bioactive agent comprises an anti-cholinergic agent.

18. A respiratory dispersion of claim 17 where the anti-cholinergic agent comprises one or more of ipratropium, atropine, or oxitropium.

19. A respiratory dispersion of claim 9 wherein said bronchodilator is salbutamol.