Engineered particles and methods of use

• US 20050074498A1
• Filed: 07/03/2003
• Published: 04/07/2005
• Est. Priority Date: 09/29/1997
• Status: Abandoned Application

• Current Assignee: Novartis Pharma AG (Novartis Ag)
• Original Assignee: Novartis Pharma AG (Novartis Ag)
• Inventors: Schutt, Ernest G., Weers, Jeffry G., Dellamary, Luis A., Tarara, Thomas E., Kabalnov, Alexey
• Application Number:
  US10/612,393
• Publication Number:
  US 20050074498A1
• Time in Patent Office: Days
• US Class Current: 424/489
• 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 39/00 General protective or antinoxious agents
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• 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

Engineered particles are provided may be used for the delivery of a bioactive agent to the respiratory tract of a patient. The particles may be used in the form of dry powders or in the form of stabilized dispersions comprising a nonaqueous continuous phase. In particularly preferred embodiments the particles may be used in conjunction with an inhalation device such as a dry powder inhaler, metered dose inhaler or a nebulizer.

Claims

1. (canceled)

2. A composition comprising microspheres, wherein said microspheres have a wall thickness of 100 to 500 nm, and a bulk density of no more than 0.1 g/cm³.

3. The composition according to claim 2, wherein the mean geometric particle size of said microspheres is less than 20 μ

m.

5. The composition according to claim 2 wherein the walls of said microspheres comprise albumin.

6. The composition according to claim 2 obtainable by spray-drying a wall-forming material in combination with a blowing agent.

7. The composition according to claim 2 wherein said microspheres comprise a bioactive agent.

8. The composition according to claim 7, wherein said microspheres comprise a protein or peptide.

9. The composition according to claim 7, wherein said microspheres comprise an active agent selected from the group consisting of insulin, growth hormone and interferon.

28. The composition according to claim 2 wherein the bulk density is no more than 0.05 g/cm³.

4. A composition comprising microspheres, wherein said microspheres have a wall thickness of 43.5 to 261 nm.

10. An inhaler comprising an inhalable formulation of microspheres wherein said microspheres have a wall thickness of 100 to 500 nm, and a bulk density of no more than 0.1 g/cm³ and wherein said microspheres comprise a bioactive agent.

11. The inhaler according to claim 10, wherein the formulation comprises the microspheres as the sole or the predominant component thereof.

12. A method for pulmonary administration of a bioactive agent wherein said method comprises the administration to the lungs of a composition which comprises microspheres having a wall thickness of 100 to 500 nm and a bulk density of no more than 0.1 g/cm³, wherein said microspheres further comprise a bioactive agent.

13. (previously presented) The method according to claim 12, wherein the mean geometric diameter of said microspheres is less than 20 μ

m.

15. The method according to claim 12, wherein the walls of said microspheres comprise albumin.

16. The method according to claim 12, wherein said microspheres are obtainable by spray-drying a wall-forming material, in combination with a blowing agent.

17. The method according to claim 12, wherein said microspheres comprise a protein or peptide.

18. The method according to claim 12, wherein said microspheres contain a bioactive agent selected from the group consisting of insulin, growth hormone and interferon.

14. A method for pulmonary administration of a bioactive agent wherein said method comprises the administration to the lungs of a composition which comprises microspheres having a wall thickness of 43.5 to 261 nm and a bulk density of no more than 0.1 g/cm³, wherein said microspheres further comprise a bioactive agent.

19. A method for diagnosis wherein said method comprises administering to a patient in need of such diagnosis, a composition which comprises microspheres having a wall thickness of 100 to 500 nm and a bulk density of no more than 0.1 g/cm³.

20. The method according to claim 19, wherein the mean geometric diameter of said microspheres is less than 20 μ

m.

22. The method according to claim 19, wherein the walls of said microspheres comprise albumin.

23. The method according to claim 19, wherein said microspheres are obtainable by spray-drying a wall-forming material, in combination with a blowing agent.

21. A method for diagnosis wherein said method comprises administering to a patient in need of such diagnosis, a composition which comprises microspheres having a wall thickness of 43.5 to 261 nm and a bulk density of no more than 0.1 g/cm³.

24. A method for preparing microparticles, wherein said method comprises spray-drying wall-forming materials and wherein said method further comprises inclusion of a blowing agent in the feedstock for spray-drying.

25. The method according to claim 24, wherein said blowing agent is selected from the group consisting of ammonium acetate, ammonium carbonate, and acids.

26. The method according to claim 24, wherein said wall-forming material is albumin.

27. A composition comprising microspheres, wherein said microspheres have a wall thickness of 100 to 500 nm, and a bulk density of no more than 0.3 g/cm³.