Dosage and formulation

• US 9,254,262 B2
• Filed: 11/09/2012
• Issued: 02/09/2016
• Est. Priority Date: 03/13/2008
• Status: Expired due to Fees

• Current Assignee: Almirall, S.A. (Grupo Corporativo Landon SL)
• Original Assignee: Almirall, S.A. (Grupo Corporativo Landon SL)
• Inventors: Serra, Gonzalo De Miquel, Casado, Rosa Lamarca
• Primary Examiner(s): Krass, Frederick
• Assistant Examiner(s): Cohen, Michael P
• Application Number:
  US13/672,893
• Publication Number:
  US 20130125884A1
• Time in Patent Office: 1,187 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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: A61M 15/0065 Inhalators with dosage or measuring devices A61M15/0028 takes precedence; dosage devices incorporated in aerosol cans B65D83/52
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present disclosure relates to pharmaceutical compositions for inhalation comprising aclidinium in the form of a dry powder of a pharmaceutically acceptable salt in admixture with a pharmaceutically acceptable dry powder carrier, providing a metered nominal dose of aclidinium equivalent to about 200 micrograms aclidinium bromide.

Claims

1. A pharmaceutical composition comprising aclidinium in the form of a dry powder of a pharmaceutically acceptable salt in admixture with a pharmaceutically acceptable dry powder carrier, wherein the pharmaceutical composition is in a dosage form which provides a) a metered nominal dose of aclidinium equivalent to 200 micrograms aclidinium bromide (plus/minus 35%), b) an emitted dose of aclidinium equivalent to 180 micrograms (plus/minus 35%) aclidinium bromide, or c) a fine particle dose of aclidinium equivalent to 60 micrograms (plus/minus 35%) aclidinium bromide, wherein the pharmaceutical composition is for inhalation.

2. The pharmaceutical composition according to claim 1, in the form of a single-dose dry powder formulation comprising a single a) metered nominal dose of aclidinium equivalent to 200 micrograms (plus/minus 35%) aclidinium bromide, b) emitted dose of aclidinium equivalent to 180 micrograms (plus/minus 35%) aclidinium bromide, or c) fine particle dose of aclidinium equivalent to 60 micrograms (plus/minus 35%) aclidinium bromide.

3. The pharmaceutical composition according to claim 1, in the form of a multi-dose dry powder formulation for administration in a multidose dry powder inhaler device calibrated to provide a metered nominal dose of aclidinium equivalent to 200 micrograms (plus/minus 35%) aclidinium bromide, b) an emitted dose of aclidinium equivalent to 180 micrograms (plus/minus 35%) aclidinium bromide, or c) a fine particle dose of aclidinium equivalent to 60 micrograms (plus/minus 35%) aclidinium bromide.

4. The pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable salt of aclidinium is aclidinium bromide.

5. The pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable carrier is lactose particles.

6. The pharmaceutical composition according to claim 1, wherein the ratio of aclidinium to carrier ranges from 1:

50 to 1;

150 by weight.

7. The pharmaceutical composition according to claim 6, wherein the ratio of aclidinium to carrier ranges from 1:

100 to 1;

150 by weight.

8. The pharmaceutical composition according to claim 1, wherein the average particle diameter of aclidinium ranges from 2 μ

m to 5 μ

m.

9. The pharmaceutical composition according to claim 1, wherein the carrier comprises particles having a d10 ranging from 90 μ

m to 160 μ

m, a d50 ranging from 170 μ

m to 270 μ

m, and a d90 ranging from 290 μ

m to 400 μ

m.

10. The pharmaceutical composition according to claim 1, further comprising an effective amount of at least one additional active agent chosen from β

2-agonists, PDE IV inhibitors, and corticosteroids.

11. The pharmaceutical composition according to claim 10, wherein the at least one additional active agent is chosen from formoterol, salmeterol, budesonide, and mometasone, wherein the at least one additional active agent is in free or pharmaceutically acceptable salt form.

12. The pharmaceutical composition according to claim 11, wherein the at least one additional active agent is formoterol fumarate in an amount ranging from about 5 micrograms to 25 micrograms per metered nominal dose.

13. The pharmaceutical composition according to claim 11, wherein the at least one additional active agent is mometasone furoate in an amount ranging from about 100 micrograms to 900 micrograms per metered nominal dose.

22. The pharmaceutical composition according to claim 12, wherein formoterol fumarate is present in an amount of about 6 micrograms per metered nominal dose.

23. The pharmaceutical composition according to claim 12, wherein formoterol fumarate is present in an amount of about 12 micrograms per metered nominal dose.

14. A method of treating a respiratory condition chosen from asthma and chronic obstructive pulmonary disease, comprising administering a pharmaceutical composition comprising aclidinium in the form of a dry powder of a pharmaceutically acceptable salt in admixture with a pharmaceutically acceptable dry powder carrier, wherein the pharmaceutical composition is in a dosage form which provides:

a) a metered nominal dose of aclidinium equivalent to 200 micrograms (plus/minus 35%) aclidinium bromide, b) an emitted dose of aclidinium equivalent to 180 micrograms (plus/minus 35%) aclidinium bromide, or c) a fine particle dose of aclidinium equivalent to 60 micrograms (plus/minus 35%) aclidinium bromide, by inhalation to a patient in need of such treatment.

15. The method of claim 14, further comprising administering an effective amount of at least one additional active agent chosen from β

2-agonists, PDE IV inhibitors, and corticosteroids.

16. The method of claim 15, wherein the at least one additional active agent is chosen from formoterol, salmeterol, budesonide, and mometasone, wherein the at least one additional agent is in free or pharmaceutically acceptable salt form.

17. The method according to claim 16, wherein the at least one additional active agent is formoterol fumarate in an amount ranging from about 5 micrograms to 25 micrograms per metered nominal dose.

18. The method according to claim 16, wherein the at least one additional active agent is mometasone furoate in an amount ranging from about 100 micrograms to 900 micrograms per metered nominal dose.

20. The method of claim 14, wherein the dose is a twice-daily dose of a) a metered nominal dose of aclidinium equivalent to 200 micrograms (plus/minus 35%) of aclidinium bromide, b) an emitted dose of aclidinium equivalent to 180 micrograms (plus/minus 35%) aclidinium bromide, or c) a fine particle dose of aclidinium equivalent to 60 micrograms (plus/minus 35%) aclidinium bromide.

21. The method of claim 14, wherein the dose is a single-daily dose of a) a metered nominal dose of aclidinium equivalent to 200 micrograms (plus/minus 35%) of aclidinium bromide, b) an emitted dose of aclidinium equivalent to 180 micrograms (plus/minus 35%) aclidinium bromide, or c) a fine particle dose of aclidinium equivalent to 60 micrograms (plus/minus 35%) aclidinium bromide.

19. A multidose dry powder inhaler device comprising a pharmaceutical composition comprising aclidinium in the form of a dry powder of a pharmaceutically acceptable salt in admixture with a pharmaceutically acceptable dry powder carrier, wherein the pharmaceutical composition is in a dosage form which provides, and the device is calibrated to deliver upon actuation:

a) a metered nominal dose of aclidinium equivalent to 200 micrograms (plus/minus 35%) of aclidinium bromide, b) an emitted dose of aclidinium equivalent to 180 micrograms (plus/minus 35%) aclidinium bromide, or c) a fine particle dose of aclidinium equivalent to 60 micrograms (plus/minus 35%) aclidinium bromide.