Aerosol formulations containing P134a and particulate medicaments

• US 5,744,123 A
• Filed: 06/05/1995
• Issued: 04/28/1998
• Est. Priority Date: 12/12/1991
• Status: Expired due to Term

• 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:
  US08/462,558
• Time in Patent Office: 1,058 Days
• Field of Search: 424/45, 424/46, 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 31/44 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]

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 medicament and a fluorocarbon or hydrogen-containing chlorofluorocarbon propellant, which formulation is substantially free of surfactant and with the proviso that said medicament is other than salmeterol, salbutamol, fluticasone propionate, beclomethasone dipropionate or a physiologically acceptable salt or solvate thereof. 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 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, the 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, wherein one of the said one or more medicaments is a bronchodilator selected from the group consisting of ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, isoetharine, tulobuterol, orciprenaline or (-)-4-amino-3,5-dichloro-α

- 6- 2-(2-pyridinyl)ethoxy!hexyl!amino!methyl!benzenemethanol or a physiologically acceptable salt thereof.

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 pirbuterol.

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

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

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

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

8. 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.

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

10. A pharmaceutical aerosol formulation consisting of (i) one or more particulate medicaments, and (ii) 1,1,1,2-tetrafluoroethane as propellant, the 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, wherein said one of the one or more medicaments is a bronchodialtor selected from the group consisting of ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, isoetharine, tulobuterol, orciprenaline or (-)-4-amino-3,5-dichloro-α

- 6- 2-(2-pyridinyl)ethoxy!hexyl!amino!methyl!benzenemethanol or a physiologically acceptable salt thereof.

11. A formulation as claimed in claim 10 wherein said medicament is pirbuterol.

12. A formulation as claimed in claim 10 which contains two or more particulate medicaments.

13. A formulation as claimed in claim 10 which comprises a particulate bronchodilatory medicament and a particulate anti-inflammatory medicament.

14. A formulation as claimed in claim 10 which comprises a particulate bronchodilatory medicament and a particulate anti-allergic medicament.

15. A formulation as claimed in claim 10 which comprises isoprenaline and cromoglycate or a physiologically acceptable salt thereof.

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

17. A formulation as claimed in claim 10 which has a respirable fraction of 20% or more by weight of medicament.