Aerosol formulations containing salmeterol xinafoate, an anticholinergic agent and tetrafluoroethane

• US 6,238,647 B1
• Filed: 11/02/1999
• Issued: 05/29/2001
• Est. Priority Date: 12/12/1991
• Status: Expired due to Fees

• Current Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• 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:
  US09/431,872
• Time in Patent Office: 574 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 31/44 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 which comprises a container capable of withstanding the vapor pressure of the propellant which container is closed with a metering valve and contains a pharmaceutical aerosol formulation which consists essentially of particulate medicament which is salmeterol xinafoate and an anticholinergic medicament which is selected from the group consisting of ipratropium, atropine, oxitropium and salts thereof, in combination and 1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% w/w of surfactant based on the weight of the 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.

5. A canister according to claim 1 wherein the medicament is present in an amount of 0.1 to 1% w/w based on the weight of formulation.

7. A canister according to claim 1 wherein the container is a metal can.

9. A canister according to claim 7 wherein the container is an aluminum can which is optionally anodised, lacquer coated and/or plastics coated.

11. A canister according to claim 9 wherein the container is an aluminum can which is plastics coated.

2. A canister suitable for delivering a pharmaceutical aerosol formulation which comprises a container capable of withstanding the vapor pressure of the propellant which container is closed with a metering valve and contains a pharmaceutical aerosol formulation which consists of particulate medicament which is salmeterol xinafoate and an anticholinergic medicament which is selected from the group consisting of ipratropium, atropine, oxitropium and salts thereof, in combination 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.

3. A canister as claimed in claim 2 wherein the anticholinergic medicament is ipratropium or a salt thereof.

4. A canister as claimed in claim 2 wherein the anticholinergic medicament is ipratropium or a salt thereof.

6. A canister according to claim 2 wherein the medicament is present in an amount of 0.1 to 1% w/w based on the weight of formulation.

8. A canister according to claim 2 wherein the container is a metal can.

10. A canister according to claim 8 wherein the container is an aluminum can which is optionally anodised, lacquer coated and/or plastics coated.

12. A canister according to claim 10 wherein the container is an aluminum can which is plastics coated.

13. A canister suitable for delivering a pharmaceutical aerosol formulation which comprises a container capable of withstanding the vapour pressure of the propellant which container is closed with a metering valve and contains a pharmaceutical aerosol formulation which consists essentially of particulate medicament which is salmeterol or a physiologically acceptable salt or solvate thereof and an anticholinergic medicament which is selected from the group consisting of ipratropium. atropine, oxitropium and salts thereof, in combination and 1,1,1,2-tetrafluoroethane as propellant, which formulation contains less than 0.0001% of surfactant, 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.