Formoterol/steroid bronchodilating compositions and methods of use thereof

• US 9,597,396 B2
• Filed: 12/27/2013
• Issued: 03/21/2017
• Est. Priority Date: 04/17/2001
• Status: Expired due to Term

• Current Assignee: Mylan Specialty L.P. (Pfizer Inc.)
• Original Assignee: Mylan Specialty L.P. (Pfizer Inc.)
• Inventors: Banerjee, Partha S., Chaudry, Imtiaz, Pham, Stephen
• Primary Examiner(s): Wang, Shengjun
• Application Number:
  US14/142,178
• Publication Number:
  US 20140171398A1
• Time in Patent Office: 1,180 Days
• Field of Search: 514/173, 514/653
• 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 31/191 having two or more hydroxy groups, e.g. gluconic acid
• CPC Class Codes: A61K 31/537 spiro-condensed or forming part of bridged ring systems
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• 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 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 9/0078 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 11/00 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

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, and a steroidal anti-inflammatory agent. 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 method for treating or ameliorating one or more symptoms of a bronchoconstrictive disorder comprising:

providing a pharmaceutical composition packaged for single dosage administration, the composition including (i) formoterol, or a pharmaceutically acceptable salt or hydrate thereof in solution; and

(ii) a steroidal anti-inflammatory agent, or a pharmaceutically acceptable salt thereof in solution;

in a pharmacologically suitable fluid comprising water that is propellant-free;

the composition as formulated 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 when stored at 5°

C., whereby greater than 80% of the initial amount of formoterol in the compositions remains at such time; and

the formoterol free base concentration is about 5 μ

g/mL to about 118 μ

g/mL, whereby the composition is formulated for direct administration to a subject in need thereof; and

without dilution, directly administering an effective amount of the composition as provided to a subject in need of such treatment.

2. The method of claim 1, wherein greater than about 90% of the initial formoterol is present in the composition after 1 month usage time at 25°

C. and 1 year storage time at 5°

C.

3. The method of claim 1, wherein the composition further comprises a tonicity adjusting agent.

4. The method of claim 3, 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.

5. The method of claim 1, wherein the pharmaceutically acceptable salt of formoterol is formoterol fumarate.

6. The method of claim 1, wherein the pharmacologically suitable fluid comprises a buffer.

7. The method of claim 6, wherein the buffer is citric acid/phosphate, acetate, barbital, cacodylate, citrate, collidine, formate, maleate, phosphate, succinate, veronal acetate, MES (2-(N-morpholino)ethanesulfonic acid), ADA (N-(2-acetamido)-2-iminodiacetic acid), ACES (N-(carbamoylmethyl)-2-aminoethanesulfonaic acid), PIPES (piperazine-N,N′

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

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

-bis(2-hydroxypropane-sulfonicacid)), EPPS(N-(2-hydroxyethyl)piperazine-N′

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

-(4-butanesulfonic acid)), TAPS(N-tris(hydroxy-methyl)methyl-3-aminopropanesulfonic acid), or AMPD (2-amino-2-methyl-1,3-propanediol) buffer.

8. The method of claim 7, wherein the buffer is citrate buffer.

9. The method of claim 8, wherein the buffer concentration is from about 0.01 mM to about 150 mM.

10. The method of claim 9, wherein the buffer concentration is from about 1 mM to about 20 mM.

11. The method of claim 10, wherein the buffer concentration is about 5 mM.

12. The method of claim 1, wherein the pH of the composition is about 4.0 to about 6.0.

13. The method of claim 12, wherein the pH of the composition is about 4.5 to about 5.5.

14. The method of claim 13, wherein the pH of the composition is about 5.0.

15. The method of claim 6, wherein the buffer is citrate buffer and the pH of the composition is about 5.0.

16. The method of claim 1, wherein the steroidal anti-inflammatory agent is beclomethasone dipropionate, beclomethasone monopropionate, flunisolide, triamcinolone acetonide, dexamethasone, tipredane, ciclesonid, rofleponide, mometasone, mometasone furoate, fluticasone, fluticasone propionate, budesonide, or a pharmaceutically acceptable salt thereof.

17. The method of claim 16, wherein the steroidal anti-inflammatory agent is budesonide, fluticasone propionate, or a pharmaceutically acceptable salt thereof.

18. The method of claim 1, wherein the steroidal anti-inflammatory agent is fluticasone propionate.

19. A method for the treatment or amelioration of one or more symptoms of bronchoconstrictive disorders, comprising:

(i) providing a packaged pharmaceutical composition comprising formoterol, or a pharmaceutically acceptable salt or hydrate thereof in solution, the pharmaceutical composition being in a pharmacologically suitable fluid comprising water that is propellant-free, 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 when stored at 5°

C. whereby greater than 90% of the initial amount of formoterol in the compositions remains at such time;

the formoterol free base concentration is about 5 μ

g/mL to about 118 μ

g/mL, whereby the composition is formulated at a concentration for direct administration to a human in need thereof;

(ii) without dilution, directly administering an effective amount of the composition as provided to a human; and

(ii) simultaneously with, prior to, or subsequent to administering the formoterol composition, administering an effective amount of a pharmaceutical composition comprising a steroidal anti-inflammatory agent, or a pharmaceutically acceptable salt thereof, in solution.

20. The method of claim 19, wherein the steroidal anti-inflammatory agent is beclomethasone dipropionate, beclomethasone monopropionate, flunisolide, triamcinolone acetonide, dexamethasone, tipredane, ciclesonid, rofleponide, mometasone, mometasone furoate, fluticasone or fluticasone propionate, or budesonide, or a pharmaceutically acceptable salt thereof.