Stable pharmaceutical solution formulations for pressurized metered dose inhalers
AssigneeChiesi Farmaceutici S.p.A.
InventorsDavid Lewis, David Ganderton, Brian Meakin, Gaetano Brambilla, Alessandra Ferraris
Life of this patent
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Abstract
An aerosol solution composition for use in an aerosol inhaler comprises an active material, a propellant containing a hydrofluoroalkane, a cosolvent and optionally a low volatility component to increase the mass median aerodynamic diameter (MMAD) of the aerosol particles on actuation of the inhaler. The composition is stabilized by using a small amount of mineral acid and a suitable can having part or all of its internal metallic surfaces made of stainless steel, anodized aluminium or lined with an inert organic coating.
Claims62
A composition, comprising 8-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]-2(1H)-quinolinone or one of its stereoisomers or a salt thereof, in a solution, wherein said solution comprises:
- at least one liquefied HFA propellant;
- at least one co-solvent selected from one or more pharmaceutically acceptable alcohols;
- and
- at least one mineral acid,
- wherein said solution has an apparent pH between about 2.5 and about 5.0.
A method for preparing an aerosol composition which comprises 8-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]-2(1H)-quinolinone or one of its stereoisomers or a salt thereof, in a solution, wherein said solution comprises:
- at least one liquefied HFA propellant;
- at least one co-solvent;
- and
- at least one mineral acid,
- wherein said solution has an apparent pH between about 2.5 and about 5.0,
- wherein said method comprises:
- (a) preparing a solution of said 8-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]-2(1H)-quinolinone or said stereoisomer or said salt thereof in one or more cosolvent(s) optionally comprising an appropriate amount of a low volatility component;
- (b) filling a device with said solution;
- (c) adding at least one mineral acid to said solution in such an amount to obtain an apparent pH between about 2.5 and about 5.0;
- (d) adding at least one propellant comprising a hydrofluoro-alkane to said solution;
- and
- (e) crimping said device with a valve and gassing.
A metered dose inhaler, which contains a pharmaceutical composition, wherein said pharmaceutical composition comprises 8-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]-2(1H)-quinolinone, or one of its stereoisomers or a salt thereof, wherein said metered dose inhaler delivers said 8-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]-2(1H)-quinolinone in a dosage of 2 to 10 mcg per single actuation of said metered dose inhaler.
A method of delivering an active agent to the respiratory tract of a subject in need thereof, comprising:
- (A) actuating a metered dose inhaler to deliver a pharmaceutical composition to said respiratory tract of said subject,
- wherein said metered dose inhaler contains said pharmaceutical composition, and said pharmaceutical composition comprises:
- (1) 8-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]-2(1H)-quinolinone;
- and optionally
- (2) at least one steroid or at least one anticholinergic atropine-like derivative,
- wherein said metered dose inhaler delivers said 8-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]-2(1H)-quinolinone in a dosage of 2 to 10 mcg per single actuation of said metered dose inhaler.
Dependencies are inferred from the claim text.