Solid peptide preparations for inhalation and their preparation

• US 20090142407A1
• Filed: 06/04/2008
• Published: 06/04/2009
• Est. Priority Date: 09/01/2000
• Status: Abandoned Application

• Current Assignee: MEDA Pharama GmbH & Company KG
• Original Assignee: MEDA Pharama GmbH & Company KG
• Inventors: Lizio, Rosario, Damm, Michael, Wolf-Heuss, Elisabeth, Sarlikiotis, Werner
• Application Number:
  US12/156,800
• Publication Number:
  US 20090142407A1
• Time in Patent Office: Days
• US Class Current: 424/499
• 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 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51

Abstract

The invention relates to solid pharmaceutical preparations, in particular for inhalatory administration in mammals, their preparation and their use such as, for example, in powder inhalers.

Claims

1. A process for preparing a fine particulate protein substance or substance mixture, said fine particulate protein substance or substance mixture having a particle size in the nanometer to micrometer range, said process comprises:

grinding a protein substance or substance mixture at a low temperature in a suspending medium, said low temperature being lower than −

30°

C., wherein said suspending medium is gaseous at ambient pressure and temperature; and

removing said suspending medium.

2. The process of claim 1, wherein said suspending medium is an unsubstituted hydrocarbon, a hydrocarbon mono- or polysubstituted by fluorine, a mixture thereof.

3. The process of claim 1, wherein said suspending medium is a hydrocarbon mono- or -polysubstituted by fluorine, selected from the group consisting of TG227, TG134a, TG152a, TG143a, and mixtures thereof.

4. The process of claim 1, wherein said suspending medium is an unsubstituted hydrocarbon selected from the group consisting of butane, isobutane, pentane, hexane, heptane and mixtures thereof.

5. The process of claim 1, wherein said suspending medium is selected from the group consisting of isobutane, pentane, hexane, heptane, TG227, TG134a, TG152a, TG143a and mixtures thereof.

6. The process of claim 1, wherein said low temperature is lower than −

40°

C.

7. The process of claim 1, further comprising adding an excipient to said suspending medium before or after grinding said protein substance or substance mixture, said excipient being selected from the group consisting of lactose, dextrose, sorbitol, mannitol, polyalcohols, xylitol, disaccharides, polysaccharides, oligosaccharides, dextrins, amino acids, solid lipids, solid phospholipids, vitamins, surfactants, polymers and mixtures thereof.

8. The process of claim 1, wherein said protein substance is abarelix, buscrelin, cetrorelix, leuprolide, cyclosporine, ganirelix, glucagon, lutropin, insulin, ramorelix, or teverelix.

9. A solid, fine-particulate pharmaceutical preparation for inhalatory administration to mammals, which comprises a fine particulate protein substance or substance mixture obtained by the process of claim 1.

10. The solid, fine-particulate pharmaceutical preparation of claim 9, wherein said active compound is abarelix, buserelin, cetrorelix, leuprolide, cyclosporine, ganirelix, glucagon, lutropin, insulin, ramorelix, or teverelix.

11. The solid, fine-particulate pharmaceutical preparation of claim 9 when filled into a powder inhaler.

12. The solid, fine-particulate pharmaceutical preparation of claim 11, wherein said powder inhaler is dry powder inhaler (DPI), multi-use dry powder inhaler (MDPI) or a blister inhaler.

19. The process of claim 1, wherein said low temperature is lower than −

50°

C.

20. The process of claim 1, wherein said low temperature is lower than −

60°

C.

21. The process of claim 1, wherein said substance or substance mixture is substantially insoluble in said suspending medium.

22. The process of claim 1, wherein said line particulate protein substance or substance mixture is useful for inhalatory therapy.

13. A process for applying a fine-particulate substance or substance mixture to a carrier material, which comprises stripping off by thorough mixing the suspending medium from a suspension of said fine particulate substance or substance mixture, said carrier material and said substance or substance mixture being substantially insoluble in said suspending medium.

14. The process of claim 13, wherein said suspending medium is selected from the group consisting of unsubstituted hydrocarbons, hydrocarbons mono- or polysubstituted by fluorine, and mixtures thereof.

15. The process of claim 13, wherein said suspending medium is selected from the group consisting of isobutane, pentane, hexane, heptane, TG227, TG134a, TG152a. TG143a and mixtures thereof.

16. The process of claim 13, wherein said carrier material is selected from the group consisting of spherical lactose having a smooth surface, agglomerated lactose having a rough surface, and mixtures thereof.

17. The process of claim 13, wherein said fine particulate substance or substance mixture has an average particle size of from about 0.1 to about 10 μ

m, and said carrier material has an average particle size of from about 10 to about 900 μ

m.

18. The process of claim 13, wherein said suspending medium further contains an excipient selected from the group consisting of lactose, dextrose, sorbitol, mannitol, polyalcohols, xylitol, disaccharides, polysaccharides, oligosaccharides, dextrins, amino acids, solid lipids, solid phopholipids, vitamins, surfactants, polymers and mixtures thereof.

23. The process of claim 13, wherein said suspending medium is selected from the group consisting of TG227, TG134a, TG152a, TG143a and mixtures thereof.