Pharmaceutical formulation comprising a phosphodiesterase inhibitor

Patent metadata

Field	Value
Publication number	US-9358224-B2
Application number	US-201113195903-A
Country	US
Kind code	B2
Filing date	Aug 2, 2011
Priority date	Aug 3, 2010
Publication date	Jun 7, 2016
Grant date	Jun 7, 2016

Abstract

Pharmaceutical formulations to be administered by pressurized metered dose inhalers (pMDIs), comprising a compound of general formula (I) may be used for the treatment and/or prevention of inflammatory or obstructive airway diseases.

First claim

The invention claimed is:

1. A pharmaceutical formulation for aerosol administration, comprising:
(a) the (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester;
(b) a propellant;
(c) a co-solvent; and
(d) a surfactant selected from the group consisting of a PEG surfactant, a PVP surfactant, and a mixture thereof.

2. A formulation according to claim 1 , which is in the form of suspension.

3. A formulation according to claim 1 , wherein said surfactant is selected from the group consisting of PEG 600, PVP (K25), and a mixture thereof.

4. A pharmaceutical formulation according to claim 1 , wherein said co-solvent is ethanol.

5. A formulation according to claim 1 , which comprises said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester in an amount of 0.02 w/w to 0.7 w/w, based on the total weight of the formulation.

6. A formulation according to claim 1 , wherein said propellant is a hydrofluoroalkane selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane, and a mixtures thereof.

7. A pressurized metered dose inhaler (pMDI), containing a formulation according to claim 1 .

8. A method of treating inflammatory or obstructive airway disease, comprising administering an effective amount of a formulation according to claim 1 to a subject in need thereof.

9. A method according to claim 8 , wherein said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester is administered at a daily therapeutically effective dose of 10 μg to 2000 μg.

10. A method according to claim 8 , wherein said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester is administered at a daily therapeutically effective dose of 20 μg to 1000 μg.

11. A method according to claim 8 , wherein said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester is administered at a daily therapeutically effective dose of 50 μg to 800 μg.

12. A method according to claim 8 , wherein said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester is administered at a daily therapeutically effective dose of 80 μg to 700 μg.

13. A method according to claim 8 , wherein said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester is administered at a daily therapeutically effective dose of 300 μg to 600 μg.

14. A formulation according to claim 1 , which comprises said 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester having an optical purity higher than 95% w/w, based on the weight of said 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester.

15. A formulation according to claim 1 , which comprises said 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester having an optical purity higher than 98% w/w, based on the weight of said 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester.

Assignees

• Bonelli Sauro
• Losi Elena
• Zambelli Enrico
• Chiesi Farma Spa

Inventors

• Bonelli Sauro
• Losi Elena
• Zambelli Enrico

Classifications

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61K31/44 Primary

  Non condensed pyridines; Hydrogenated derivatives thereof · CPC title

• A61K9/008

  comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI] · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61P11/06

  Antiasthmatics · CPC title