Aerosol formulations containing P134a and particulate medicament

• US 5,922,306 A
• Filed: 04/15/1998
• Issued: 07/13/1999
• Est. Priority Date: 12/12/1991
• Status: Expired due to Term

• 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:
  US09/060,110
• Time in Patent Office: 454 Days
• Field of Search: 424/45, 424/46, 514/937, 514/826
• 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 formulation consisting essentially of (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.

2. A formulation as claimed in claim 1 which is free of surfactant.

3. A formulation as claimed in claim 1 wherein said medicament is an anti-allergic, a bronchodilator or an anti-inflammatory steroid.

4. A formulation as claimed in claim 1 wherein said medicament is a bronchodilator.

5. A formulation as claimed in claim 1 wherein said medicament is pirbuterol or a physiologically acceptable salt thereof.

6. A formulation as claimed in claim 1 which contains two or more particulate medicaments.

7. A formulation as claimed in claim 1 which comprises a particulate bronchodilatory medicament and a particulate anti-inflammatory medicament.

8. A formulation as claimed in claim 1 which comprises a particulate bronchodilatory medicament and a particulate anti-allergic medicament.

9. A formulation as claimed in claim 1 which comprises isoprenaline and cromoglycate or a physiologically acceptable salt thereof.

10. A formulation as claimed in claim 1 which contains 0.01 to 1% w/w of medicament relative to the total weight of the formulation.

11. A formulation as claimed in claim 1 which has a respirable fraction of 20% or more by weight of medicament.

12. A formulation as claimed in claim 1 wherein said medicament is an anti-allergic medicament selected from the group consisting of ketotifen, nedocromil and physiologically acceptable salts thereof.

13. A formulation as claimed in claim 1 wherein said medicament is an anti-inflammatory medicament selected from the group consisting of budesonide and triamcinolone acetonide.

14. A formulation as claimed in claim 1 wherein said medicament is an anti-inflammatory medicament which is flunisolide.

15. A formulation as claimed in claim 1 wherein said medicament is an anti-cholinergic medicament selected from the group consisting of ipratropium, atropine, oxitropium and physiologically acceptable salts thereof.

16. A formulation as claimed in claim 1 wherein said medicament is a xanthine selected from the group consisting of aminophylline, choline theophyllinate, lysine theophyllinate, theophylline and physiologically acceptable salts thereof.

17. A formulation as claimed in claim 1 wherein said medicament is cromoglycate or a physiologically acceptable salt thereof.

19. A formulation as claimed in claim 1 wherein said medicament is an anti-allergic, a bronchodilator or an anti-inflammatory steroid.

20. A formulation as claimed in claim 1 wherein said medicament is a bronchodilator.

21. A formulation as claimed in claim 1 wherein said medicament is pirbuterol or a physiologically acceptable salt thereof.

22. A formulation as claimed in claim 1 which contains two or more particulate medicaments.

23. A formulation as claimed in claim 1 which comprises a particulate bronchodilatory medicament and a particulate anti-inflammatory medicament.

24. A formulation as claimed in claim 1 which comprises a particulate bronchodilatory medicament and a particulate anti-allergic medicament.

25. A formulation as claimed in claim 1 which comprises isoprenaline and cromoglycate or a physiologically acceptable salt thereof.

26. A formulation as claimed in claim 1 which contains 0.01 to 1% w/w of medicament relative to the total weight of the formulation.

27. A formulation as claimed in claim 1 which has a respirable fraction of 20% or more by weight of medicament.

28. A formulation as claimed in claim 1 wherein said medicament is an anti-allergic medicament selected from the group consisting of ketotifen, nedocromil and physiologically acceptable salts thereof.

29. A formulation as claimed in claim 1 wherein said medicament is an anti-inflammatory medicament selected from the group consisting of budesonide and triamcinolone acetonide.

30. A formulation as claimed in claim 1 wherein said medicament is an anti-inflammatory medicament which is flunisolide.

31. A formulation as claimed in claim 1 wherein said medicament is an anti-cholinergic medicament selected from the group consisting of ipratropium, atropine, oxitropium and physiologically acceptable salts thereof.

18. A pharmaceutical aerosol formulation consisting of (i) one or more particulate medicaments, and (ii) 1,1,1,2-tetrafluoroethane as propellant, 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.

32. A formulation as claimed in claim 18 wherein said medicament is a xanthine selected from the group consisting of aminophylline, choline theophyllinate, lysine theophyllinate, theophylline and physiologically acceptable salts thereof.

33. A pharmaceutical aerosol formulation consisting essentially of (i) one or more particulate medicaments, and (ii) 1,1,1,2-tetrafluoroethane as propellant, which formulation is free of surfactant, 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 which formulation contains less than 0.866% w/w of medicament relative to the total weight of the formulation.

34. A pharmaceutical aerosol formulation consisting essentially of (i) one or more particulate medicaments, and (ii) 1,1,1,2-tetrafluoroethane as propellant, which formulation is free of surfactant, 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 of solvate thereof and which formulation contains 0.005 to 0.659% w/w medicament relative to the total weight of the formulation.