Canister containing aerosol formulations containing P134a and particulate medicaments

• US 5,676,929 A
• Filed: 05/19/1995
• Issued: 10/14/1997
• Est. Priority Date: 12/12/1991
• Status: Expired due to Term

• Current Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.), Solvay Interox Limited
• Original Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Inventors: Wyatt, David Andrew, Taylor, Anthony James, Akehurst, Rachel Ann
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US08/444,743
• Time in Patent Office: 879 Days
• Field of Search: 222/402.1, 222/635, 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 31/44 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 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• 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: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 : Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 : Antiasthmatics
• CPC Class Codes: A61P 11/08 : Bronchodilators

Abstract

This invention relates to aerosol formulations of use for the administration of medicaments by inhalation, in particular a pharmaceutical aerosol formulation which comprises particulate salbutamol and physiologically acceptable salts and solvates thereof and a fluorocarbon or hydrogen-containing chlorofluorocarbon propellant, which formulation is substantially free of surfactant. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as defined is also described.

Claims

1. A canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is closed with a metering valve and contains a pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is salbutamol or a physiologically acceptable salt or solvate thereof and 1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% w/w surfactant based upon the weight of medicament, the particulate medicament 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, and with the provisos that when said formulation consists of salbutamol and 1,1,1,2-tetrafluoroethane in a weight ratio of 0.05:

18, said salbutamol is present in the form of a physiologically acceptable salt and that when said formulation consists of salbutamol or salbutamol sulphate and 1,1,1,2-tetrafluoroethane the weight to weight ratio of medicament to propellant is other than 69;

7900 or 0.866%.

4. A canister as claimed in claim 1 wherein the container is plastics-coated, lacquer coated or anodized.

5. A canister as claimed in claim 1 wherein the container is a metal can.

6. A canister as claimed in claim 1 wherein the container is a metal can, which is plastics-coated.

7. A canister as claimed in claim 1 wherein the container is an aluminum can.

8. A canister as claimed in claim 1 wherein the container is an aluminum can which is plastics-coated.

9. A canister as claimed in claim 1 wherein the formulation is free of surfactant.

10. A canister as claimed in claim 1 wherein the salbutamol is in the form of its sulphate salt.

11. A metered dose inhaler which comprises a canister as claimed in claim 1 fitted into a channelling device for nasal or oral inhalation of the pharmaceutical aerosol formulation.

12. A canister as claimed in claim 1 wherein the medicament is present in an amount of 0.01% to 1% w/w based upon the total weight of the formulation.

13. A canister as claimed in claim 1 wherein the formulation has a respirable fraction of 20% or more by weight of the medicament.

22. A canister as claimed in claim 1 wherein the pharmaceutical aerosol formulation is in a form for inhalation into lungs of a patient.

2. A canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is closed with a metering valve and contains a pharmaceutical aerosol formulation consisting of particulate medicament which is salbutamol or a physiologically acceptable salt or solvate thereof and 1,1,1,2-tetrafluoroethane as propellant, the particulate medicament 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, and with the provisos that when said formulation consists of salbutamol and 1,1,1,2-tetrafluoroethane in a weight ratio of 0.05:

18, said salbutamol is in the form of a physiologically acceptable salt and that when said formulation consists of salbutamol or salbutamol sulphate and 1,1,1,2-tetrafluoroethane the weight to weight ratio of medicament to propellant is other than 69;

7900 or 0.866%.

14. A canister as claimed in claim 2 wherein the container is plastics-coated, lacquer coated or anodized.

15. A canister as claimed in claim 2 wherein the container is a metal can.

16. A canister as claimed in claim 2 wherein the container is a metal can, which is plastics-coated.

17. A canister as claimed in claim 2 wherein the container is an aluminum can.

18. A canister as claimed in claim 2 wherein the container is an aluminum can which is plastics-coated.

19. A canister as claimed in claim 2 wherein the salbutamol or physiologically acceptable salt or solvate thereof is present in an amount of 0.01 to 1% w/w based upon the total weight of the formulation.

20. A canister as claimed in claim 2 wherein the formulation has a respirable fraction of 20% or more by weight of salbutamol or physiologically acceptable salt or solvate thereof.

21. A metered dose inhaler which comprises a canister as claimed in claim 2 fitted into a channelling device for nasal or oral inhalation of the pharmaceutical aerosol formulation.

23. A canister as claimed in claim 2 wherein the salbutamol is in the form of its sulphate salt.

3. A canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is a plastics-coated aluminum can and is closed with a metering valve and contains a pharmaceutical aerosol formulation consisting essentially of a particulate medicament which is salbutamol sulphate and 1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% w/w surfactant based upon the weight of salbutamol sulphate, the particulate medicament being present in an amount of 0.01% to 1% w/w relative to the total weight of the formulation and having a particle size of less than 100 microns, and with the provisos than when said formulation consists of salbutamol and 1,1,1,2-tetrafluoroethane in a weight ratio of 0.05:

18, said salbutamol is present in the form of a physiologically acceptable salt and that when said formulation consists of salbutamol or salbutamol sulphate and 1,1,1,2-tetrafluoroethane the weight to weight ratio of medicament to propellant is other than 69;

7900 or 0.866%.

24. A canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is closed with a metering valve and contains a pharmaceutical aerosol formulation consisting essentially of particulate medicaments which are salbutamol and beclomethasone dipropionate and physiologically acceptable salts and solvates thereof, and 1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% w/w surfactant based upon the weight of particulate medicaments, 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.

26. A canister as claimed in claim 24 in which the formulation is free of surfactant.

27. A canister as claimed in claim 24 in which the salbutamol is in the form of its sulphate salt.

28. A canister as claimed in claim 24 wherein the particulate medicaments are present in an amount of 0.01% to 1% w/w relative to the total weight of the formulation.

25. A canister suitable for delivering a pharmaceutical aerosol formulation for inhalation therapy which comprises a container capable of withstanding the vapor pressure of the propellant used, which container is closed with a metering valve and contains a pharmaceutical aerosol formulation consisting of particulate medicaments which are salbutamol and beclomethasone dipropionate and physiologically acceptable salts and solvates thereof, and 1,1,1,2-tetrafluoroethane as propellant, 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.

29. A canister as claimed in claim 25 in which the salbutamol is in the form of its sulphate salt.

30. A canister as claimed in claim 25 wherein the particulate medicaments are present in an amount of 0.01% to 1% w/w relative to the total weight of the formulation.