PHARMACEUTICAL FORMULATION COMPRISING CICLESONIDE

• US 20140179650A1
• Filed: 12/18/2013
• Published: 06/26/2014
• Est. Priority Date: 12/21/2012
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: AVEN, Michael, ALBRECHT, Balazs, HAUSMANN, Matthias, LAMAR, Janine, LANG, Ingo, FRANZMANN, Benjamin
• Granted Patent: US 10,925,964 B2
• Time in Patent Office: Days
• US Class Current: 514/174
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system

Abstract

The invention relates to the field of medicine, in particular to the field of veterinary medicine. The invention relates to a pharmaceutical (medicament) formulation of glucocorticoids, especially ciclesonide or a pharmaceutically acceptable derivative thereof.

Claims

1. A pharmaceutical formulation comprising ciclesonide and/or des-ciclesonide as an active substance, wherein said formulation is an ethanolic solution or a solution containing a mixture of ethanol and water.

2. The pharmaceutical formulation according to claim 1, wherein said active substance is in the form of tautomers, enantiomers, mixtures of enantiomers, racemates, solvates or hydrates.

3. The pharmaceutical formulation according to claim 1, wherein said formulation comprises at least one pharmacologically acceptable acid.

4. The pharmaceutical formulation according to claim 1, wherein said formulation comprises pharmacologically acceptable excipients and/or solvents.

5. The pharmaceutical formulation according to claim 1, wherein the proportion of ethanol in the mixture of ethanol and water is in the range of 85-100% V/V.

6. The pharmaceutical formulation according to claim 5, wherein the proportion of ethanol in the mixture of ethanol and water is in the range of 90-95% V/V.

7. The pharmaceutical formulation according to claim 6, wherein the proportion of ethanol in the mixture of ethanol and water is 90% V/V.

8. The pharmaceutical formulation according to claim 1, wherein said formulation is a solution for inhalation.

9. The pharmaceutical formulation according to claim 1, wherein −

log₁₀[H+] is in the range of 4.0 to 4.6.

10. The pharmaceutical formulation according to claim 1, wherein one active substance is ciclesonide or a pharmaceutically acceptable salt thereof.

11. The pharmaceutical formulation according to claim 10, wherein said active substance is in the R-enantiomer form.

12. The pharmaceutical formulation according to claim 10, wherein said active substance is in a concentration of 0.1-5 g/100 mL.

13. The pharmaceutical formulation according to claim 12, wherein said active substance is in a concentration of 0.7-3.1 g/100 mL.

14. The pharmaceutical formulation according to claim 13, wherein said active substance is in a concentration of 3 g/100 mL.

15. The pharmaceutical formulation according to claim 4, wherein the pharmacologically acceptable excipient and/or solvent comprises one or more of the excipients and/or solvents selected from the group consisting of:

water, a pharmaceutically acceptable organic solvent or mixtures thereof.

16. The pharmaceutical formulation according to claim 15, wherein said pharmaceutically acceptable organic solvent is a mono- or polyfunctional alcohol.

17. The pharmaceutical formulation according to claim 16, where such organic solvent is glycerol or propanol.

18. The pharmaceutical formulation according to claim 15, wherein said formulation comprises additional excipients and/or solvents.

19. The pharmaceutical formulation according to claim 3, wherein the pharmacologically acceptable acid an inorganic acid.

20. The pharmaceutical formulation according to claim 19, wherein said inorganic acid is selected from hydrochloric acid, phosphoric acid and hydrobromic acid.

21. The pharmaceutical formulation according to claim 1, wherein the formulation is administered via an (equine) inhaler device.

22. A method of preparing a pharmaceutical formulation according to claim 1, comprising the following steps:

a. Dissolving ciclesonide in a solvent comprising ethanol and water,

b. Adding a fixed amount of acid, preferably hydrochloric acid (HCl), most preferably as a 0.1 or 1.0 molar solution.

23. The method according to claim 22, wherein the proportion of ethanol in the solvent of step a) is in the range of 85-100% V/V.

24. The method according to claim 23, wherein the proportion of ethanol in the solvent of step a) is in the range of 90-95% V/V.

25. The method according to claim 24, wherein the proportion of ethanol in the solvent of step a) is 90% V/V ethanol.

26. The method according to claim 22, wherein ciclesonide is first dissolved in ethanol and the amount of water needed to reach the target solvent composition is then added.

27. The method according to claim 22, comprising the additional step of mixing until a homogeneous solution is formed.

28. The method according to claim 22, comprising the additional step of filtering the solution through one or more filters with a pore size of maximum 1.0 μ

m for at least one of the filters.

29. The method according to claim 28, wherein said pore size maximum for at least one of the filters is 0.2 μ

m.

30. The method according to claim 22, further comprising the additional step of filling said solution into containers appropriate for long term storage and for use with an inhaler.

31. A pharmaceutical formulation comprising ciclesonide as active substance obtainable by a method according to claim 22.

32. An inhalation kit comprising a pharmaceutical formulation according to claim 1, an inhaler device and an instruction leaflet comprising instructions and directions for use.

33. The inhalation kit according to claim 32, wherein said inhaler device nebulizes said pharmaceutical formulation.

34. The inhalation kit according to claim 32, where said inhaler device is a pressurized metered dose inhaler.

35. The inhalation kit according to claim 32, wherein said inhaler device is an aqueous/ethanolic droplet inhaler.

36. The inhalation kit according to claim 34 wherein said inhaler device is a RESPIMAT®

inhaler or another inhaler using the RESPIMAT®

aerosol-generating technology.

37. The inhalation kit according to claim 32, wherein said inhaler device comprises an adapter for equine use.