Aerosol formulations containing P134a and particulate medicament

• US 6,306,369 B1
• Filed: 04/28/2000
• Issued: 10/23/2001
• Est. Priority Date: 12/12/1991
• Status: Expired due to Fees

• Current Assignee: Glaxo Group Limited (GSK plc)
• Original Assignee: Glaxo Group Limited (GSK plc)
• Inventors: Wyatt, David Andrew, Taylor, Anthony James, Akehurst, Rachel Ann
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US09/559,574
• Time in Patent Office: 543 Days
• Field of Search: 424/45, 424/46
• US Class Current: 424/45
• 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 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• 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 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• 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 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 31/4741 condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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: A61K 9/145 : with organic compounds
• 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

Abstract

A pharmaceutical formulation comprising (i) one or more particulate medicaments, and (ii) 1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% w/w surfactant based upon the weight of medicament, particulate medicament being present in an amount from 0.005 to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns, with the proviso that said medicament is other than salmeterol, salbutamol, fluticasone propionate, beclomethasone dipropionate or a physiologically acceptable salt or solvate thereof and with the proviso that when said formulation consists of betamethasone, ergotamine tartrate or sodium cromoglycate and 1,1,1,2-tetrafluoroethane the weight to weight ratio of medicament to propellant is other than 69:7900 or 0.866% w/w.

Claims

1. A pharmaceutical aerosol formulation comprising:

(a) an effective amount of a particulate bronchodilatory medicament;

(b) an effective amount of a particulate anti-inflammatory medicament; and

(c) 1,1,1,2-tetrafluoroethane as propellant;

which formulation contains less than 0.0001% surfactant by weight of the medicaments;

with the proviso that such medicaments are other than salmeterol, salbutamol, fluticasone propionate, beclomethasone dipropionate or a physiologically acceptable salt or solvate thereof, and wherein the particulate medicaments being present in an amount of 0.005% to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

2. A pharmaceutical aerosol formulation according to claim 1 comprising:

(a) an effective amount of a particulate bronchodilatory medicament;

(b) an effective amount of a particulate anti-inflammatory medicament; and

(c) 1,1,1,2-tetrafluoroethane as propellant;

which formulation is free of surfactant.

3. A pharmaceutical aerosol formulation according to claim 1 wherein the bronchodilatory medicament is selected from the group consisting of ephedrine, epinephrine, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, and (−

)-4-amino-3,5-dichloro-α

-[[[6-[2-(2-pyridinyl)ethoxy]hexyl]amino]-methyl]benzenemethanol and salts thereof.

4. A pharmaceutical aerosol formulation according to claim 3 wherein the bronchodilatory medicament is formoterol or a salt thereof.

5. A pharmaceutical aerosol formulation according to claim 1 wherein the bronchodilatory medicament is selected from the group consisting of isoetharine, tulobuterol, orciprenaline and salts thereof.

6. A pharmaceutical aerosol formulation according to claim 1 wherein the bronchodilatory medicament is an anti-cholinergic medicament.

7. A pharmaceutical aerosol formulation according to claim 6 wherein the anti-cholinergic medicament is ipratropium or a salt thereof.

8. A pharmaceutical aerosol formulation according to claim 1 wherein the anti-inflammatory medicament is an anti-allergic medicament.

9. A pharmaceutical aerosol formulation according to claim 8 wherein the anti-allergic medicament is sodium cromoglycate.

10. A pharmaceutical aerosol formulation according to claim 9 comprising sodium cromoglycate as anti-inflammatory medicament and isoprenaline as bronchodilatory medicament.

11. A pharmaceutical aerosol formulation according to claim 1 wherein the anti-inflammatory medicament is a steroidal anti-inflammatory medicament.

12. A pharmaceutical aerosol formulation according to claim 11 wherein the steroidal anti-inflammatory medicament is selected from the group consisting of flunisolide, tipredane and triamcinolone acetonide.

13. A pharmaceutical aerosol formulation according to claim 11 wherein the steroidal anti-inflammatory medicament is budesonide.

14. A pharmaceutical aerosol formulation according to claim 11 comprising (i) formoterol or a salt thereof as bronchodilatory medicament and (ii) budesonide as anti-inflammatory medicament.

17. A pharmaceutical aerosol formulation according to claim 1 containing 0.01-1% w/w of medicament relative to the total weight of the formulation.

18. A method of treatment of respiratory disorders by inhalation therapy which comprises administering to a patient a pharmaceutical aerosol formulation according to claim 1.

19. A method of treatment of respiratory disorders by inhalation therapy which comprises administering to a patient a pharmaceutical aerosol formulation according to claim 14.

15. A pharmaceutical aerosol formulation consisting essentially of:

(a) an effective amount of particulate formoterol or a salt thereof as bronchodilatory medicament;

(b) an effective amount of particulate budesonide as anti-inflammatory medicament; and

(c) 1,1,1,2-tetrafluoroethane as propellant;

which formulation contains less than 0.0001% surfactant by weight of the medicaments and wherein the particulate medicaments being present in an amount of 0.005% to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.

20. A method of treatment of respiratory disorders by inhalation therapy which comprises administering to a patient a pharmaceutical aerosol formulation according to claim 15.

16. A pharmaceutical aerosol formulation consisting of:

(a) an effective amount of particulate formoterol or a salt thereof as bronchodilatory medicament;

(b) an effective amount of particulate budesonide as anti-inflammatory medicament; and

(c) 1,1,1,2-tetrafluoroethane as propellant and wherein the particulate medicaments being present in an amount of 0.005% to 5% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns.