Formoterol and mometasone aerosol formulations

• US 20050255049A1
• Filed: 03/21/2003
• Published: 11/17/2005
• Est. Priority Date: 04/05/2002
• Status: Active Grant

• Current Assignee: Kindeva Drug Delivery L.P.
• Original Assignee: 3M Innovative Properties Company (3M Company)
• Inventors: Boswell, Susannah C, Jinks, Phillip A, Slowey, Alexander D
• Granted Patent: US 8,252,268 B2
• Time in Patent Office: Days
• US Class Current: 424/46
• 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 31/573 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 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61K 9/124 characterised by the propellant
• CPC Class Codes: A61L 9/14 using sprayed or atomised substances including air-liquid contact processes
• CPC Class Codes: A61P 11/06 Antiasthmatics

Abstract

A pharmaceutical aerosol formulation comprising particles of (a) formoterol or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof and (b) mometasone or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative, thereof dispersed in a propellant selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane and a mixture thereof, and a bulking agent having a mass median diameter of less than one micron.

Claims

1. A pharmaceutical aerosol formulation comprising particles of (a) formoterol or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof and (b) mometasone or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof dispersed in a propellant selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane and a mixture thereof, and a bulking agent having a mass median diameter of less than one micron.

2. A pharmaceutical aerosol formulation according to claim 1, wherein the formoterol is in the form of formoterol fumarate.

3. A pharmaceutical aerosol formulation according to claim 2, wherein the formoterol is in the form of formoterol fumarate dihydrate.

4. A phamaceutical aerosol formulation of claim 1, wherein the mometasone is in the form of mometasone furoate.

5. A pharmaceutical aerosol formulation according to claim 1, wherein the formoterol is present in an amount of about 0.06 to 0.60 mg per ml.

6. A pharmaceutical aerosol formulation according to claim 1, wherein the mometasone is present in amount of about 0.5 to 15.0 mg per ml.

7. A pharmaceutical aerosol formulation according to claim 1, wherein the bulking agent is selected from groups consisting of ascorbic acid, saccharides, polysaccharides, amino acids, organic and inorganic salts, urea and propyliodone.

8. A pharmaceutical aerosol formulation according to claim 7, wherein the bulking agent is selected from lactose, DL-alanine, glucose, D-galactose, D(+)trehalose dihydrate, sucrose, maltose, D(+)raffinose pentahydrate, sodium saccharin, starches, modified celluloses, dextrins, dextrans, glycine, sodium chloride, calcium carbonate, sodium tartrate and calcium lactate.

9. A pharmaceutical aerosol formulation according to claim 7 wherein the bulking agent is lactose.

10. A pharmaceutical aerosol formulation according to claim 1, wherein the weight ratio of formoterol to bulking agent is in the range 1:

0.1 to 1;

30.

11. A pharmaceutical aerosol formulation according to claim 1, wherein the bulking agent has a mass median diameter of not more than 300 nm.

12. A pharmaceutical aerosol formulation according to claim 1, wherein the formulation further comprises a surfactant.

13. A pharmaceutical aerosol formulation according to claim 1, wherein the formulation further comprises ethanol.

14. A pharmaceutical aerosol formulation according to claim 13, wherein ethanol is present in amount of from 0.1 to 5% by weight of the formulation.

15. A dispenser comprising an aerosol vial equipped with a dispensing valve, said aerosol vial containing a formulation according to claim 1.

17. A method of preparing a formulation according to claim 1, the method comprising the steps of (i) forming a slurry of bulking agent with a component of the formulation;

(ii) subjecting the slurry to high pressure homogenization; and

(iii) combining the resulting slurry with other components of the aerosol formulation.

16. A dispenser according to claim 16, wherein an interior surface of the aerosol vial is coated with a fluorocarbon polymer.