Bronchodilating Beta-agonist compositions and methods

• US 8,623,922 B2
• Filed: 12/23/2011
• Issued: 01/07/2014
• Est. Priority Date: 07/10/2003
• Status: Active Grant

• Current Assignee: Dey Pharma LP (Pfizer Inc.)
• Original Assignee: Dey Pharma LP (Pfizer Inc.)
• Inventors: Banerjee, Partha S., Chaudry, Imtiaz A., Pham, Stephen
• Primary Examiner(s): HENLEY III, RAYMOND J
• Application Number:
  US13/336,972
• Publication Number:
  US 20120309837A1
• Time in Patent Office: 746 Days
• Field of Search: 514/561, 514/630
• US Class Current: 514/630
• 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 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• 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: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators

Abstract

Bronchodilating compositions and methods are provided. The compositions are intended for administration as a nebulized aerosol. In certain embodiments, the compositions contain formoterol, or a derivative thereof. Methods for treatment, prevention, or amelioration of one or more symptoms of bronchoconstrictive disorders using the compositions provided herein are also provided.

Claims

1. A pharmaceutical composition, comprising formoterol, or a pharmaceutically acceptable derivative thereof selected from the group consisting of salts, esters, enol ethers, enol esters, acids, bases, solvates, hydrates and prodrugs, in a pharmacologically suitable fluid, wherein the composition is stable during long term storage and the fluid comprises water, and wherein the formoterol free base concentration is about 0.08 μ

g/mL up to about 128 μ

g/mL.

2. The pharmaceutical composition of claim 1, wherein the composition has an estimated shelf-life of greater than 1 month usage time at 25°

C. and greater than or equal to 1 year storage time at 5°

C.

3. The pharmaceutical composition of claim 1, wherein greater than about 80% of the initial formoterol is present after 1 month usage time at 25°

C. and 1 year storage time at 5°

C.

4. The pharmaceutical composition of claim 1 that has been nebulized.

5. The pharmaceutical composition of claim 1, wherein the pharmacologically suitable fluid comprises a polar solvent.

6. The pharmaceutical composition of claim 5, wherein the polar solvent is a protic solvent.

7. The pharmaceutical composition of claim 1, further comprising a tonicity adjusting agent.

8. The pharmaceutical composition of claim 7, wherein the tonicity adjusting agent is ammonium carbonate, ammonium chloride, ammonium lactate, ammonium nitrate, ammonium phosphate, ammonium sulfate, ascorbic acid, bismuth sodium tartrate,, calcium chloride, calcium disodium edetate, calcium gluconate, calcium lactate, citric acid, dextrose, diethanolamine, dimethylsulfoxide, edetate disodium, edetate trisodium monohydrate, fluorescein sodium, fructose, galactose, glycerin, lactic acid, lactose, magnesium chloride, magnesium sulfate, mannitol, polyethylene glycol, potassium acetate, potassium chlorate, potassium chloride, potassium iodide, potassium nitrate, potassium phosphate, potassium sulfate, propylene glycol, silver nitrate, sodium acetate, sodium bicarbonate, sodium biphosphate, sodium bisulfite,, sodium bromide, sodium cacodylate, sodium carbonate, sodium chloride, sodium citrate, sodium iodide, sodium lactate, sodium metabisulfite, sodium nitrate;

sodium nitrite, sodium phosphate, sodium propionate, sodium succinate, sodium sulfate, sodium sulfite, sodium tartrate, sodium thiosulfate, sorbitol, sucrose, tartaric acid,, urea, urethan, uridine or zinc sulfate.

9. The pharmaceutical composition of claim 7, wherein the tonicity adjusting agent is sodium chloride.

10. The pharmaceutical composition of claim 1, wherein the pharmacologically suitable fluid comprises a buffer.

11. The pharmaceutical composition of claim 10, wherein the buffer is citric acid/phosphate, acetate, barbital, Britton-Robinson, cacodylate, citrate, collidine, formate, maleate, McIlvaine, phosphate, Prideaux-Ward, succinate,), verona acetate, MES (2-(N-morpholino)ethanesulfonic acid), ADA (N-(2-acetamido)-2-iminodiacetic acid), ACES (N-(carbamoylmethyl)-2-aminoethanesulfonic acid), PIPES (piperazine-N,N′

-bis(2-ethanesulfonic acid)), MOPSO (3-(N-morpholino)-2-hydroxypropanesulfonic acid), BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), MOPS (3-(N-morpholino)propanesulfonic acid), TES (N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid), HEPES (N-(2-hydroxyethyl)piperazine-N-(2-ethanesulfonic 20 acid), DIPSO (3-(N,N-bis(2-hydroxyethyl)amino)-2-hydroxypropanesulfonic acid), MOBS (4-(N-morpholino)butanesulfonic acid), TAPSO (3-(N-tris(hydroxymethyl)-methylamino)-2-hydroxypropanesulfonic acid), HEPPSO(N-(2-hydroxyethyl)piperazine-N′

-(2-hydroxypropanesulfonic acid), POPSO (piperazine-N,N′

-bis(2-hydroxypropanesulfonic acid)), EPPS(N-(2-hydroxyethyppiperazine-N′

-(3-propanesulfonic acid), TRICINE (N-tris(hydroxymethyl)methylglycine), GLY-GLY (glycylglycine), BICINE (N,N-bis(2-hydroxyethyl)glycine), HEPBS (N-(2-hydroxyethyl)piperazine-N′

-(4-butanesulfonic acid)), TAPS(N˜

tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid), or AMPD (2-amino-2-methyl-1,3-propanediol) buffer.

12. The pharmaceutical composition of claim 10;

wherein the buffer comprises citric acid/phosphate buffer, acetate buffer, citrate buffer or phosphate buffer.

13. The pharmaceutical composition of claim 10, wherein the buffer is citrate buffer.

14. The pharmaceutical composition of claim 13, wherein the buffer concentration is from about 0.01 mM to about 150 mM.

15. The pharmaceutical composition of claim 13, wherein the buffer concentration is from about 1 mM to about 50 mM.

16. The pharmaceutical composition of claim 13, wherein the buffer concentration is from about 1 mM to about 20 mM.

17. The pharmaceutical composition of claim 13, wherein the buffer concentration is about 20 mM.

18. The pharmaceutical composition of claim 13, wherein the buffer concentration is about 5 mM.

19. The pharmaceutical composition of claim 8, wherein the ionic strength of the composition is about 0 to about 0.4.

20. The pharmaceutical composition of claim 8, wherein the ionic strength of the composition is about 0.05 to about 0.16.