Drug – bio-affecting and body treating compositions – Effervescent or pressurized fluid containing – Organic pressurized fluid
Reexamination Certificate
1998-06-19
2002-09-17
Bawa, Raj (Department: 1616)
Drug, bio-affecting and body treating compositions
Effervescent or pressurized fluid containing
Organic pressurized fluid
C424S046000, C424S489000
Reexamination Certificate
active
06451285
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to pressurized metered dose inhalers and aerosol formulations for inhalation therapy.
BACKGROUND OF THE INVENTION
Because of environmental considerations, chlorohydrocarbon and chlorofluorocarbon propellants for aerosol formulations for medical uses have been largely replaced by hydrofluoroalkanes such as 1,1,1,2-tetrafluoroethane (“HFA-134a”) and 1,1,1,2,3,3,3,-heptafluoropropane (“HFA-227ea”) that have been identified as safe for use in pressurized metered dose inhalers.
Such medicinal aerosol formulations are generally of the solution or suspension type. Each type is composed of, at least, the medicament and the propellant. Some formulations also include one or more special purpose adjuvants such as a cosolvent or a surfactant (EP 0 372777). Conventional aerosol solution formulations contain low concentrations of a cosolvent more polar than the propellant. Conventional aerosol suspension formulations contain a surfactant rather than a cosolvent on a theory that the surfactant would prevent agglomeration of the particles, their adhesion to the walls of the aerosol container, and provide for lubrication of the dispensing valve (“actuator”). (U.S. Pat. No. 3,014,844).
Ethanol has been used as a cosolvent. However, previous teachings (see, e.g., EP 0 616525) have taught away from using concentrations of ethanol greater than 5% for solution aerosol formulations for &bgr;-agonists. Historically, ethanol concentrations greater than 5% have been used only for steroid-based formulations with hydrofluoroalkane propellants.
The &bgr;-agonist drug, formoterol (“eformoterol” in Europe) and its derivatives, have proven difficult to formulate in conventional aerosols. Such formulations have exhibited short shelf-lives and require refrigeration. Refrigeration is undesirable because many patients are required to carry the aerosol canisters on their persons. There remains, therefore, an important need for aerosol formulations for &bgr;-agonist drugs such as formoterol and its derivatives that remain chemically and physically stable during storage at ambient conditions of temperature and humidity.
SUMMARY OF THE INVENTION
An objective of the present invention is to provide a pressurized metered dose inhaler that contains a stable formulation of a &bgr;-agonist drug, which does not require the use of refrigeration.
Another objective of the present invention is to provide a stable formulation of a &bgr;-agonist drug that is suitable for use as an aerosol, which does not require the use of refrigeration.
The above objectives and other objectives are surprisingly achieved by the following. The present invention provides a novel pressurized metered dose inhaler comprising a container equipped with a metering valve and containing a pressurized aerosol formulation formulated from a composition comprising:
a &bgr;-agonist drug;
at least one fluoroalkane propellant; and
greater than 5% by weight, based on total weight of the aerosol formulation, of a solvent that is capable of solubilizing or dissolving the &bgr;-agonist drug.
The invention further provides a novel pressurized metered dose inhaler comprising a container equipped with a metering valve and containing a pressurized aerosol formulation formulated from a composition comprising:
particles of a &bgr;-agonist drug;
at least one fluoroalkane propellant; and
a surfactant that is capable of forming a suspension of the particles of &bgr;-agonist drug.
The invention also provides a novel aerosol formulation adapted for use in a pressurized aerosol container, said aerosol formulation being formulated from a composition comprising:
a &bgr;-agonist drug;
at least one fluoroalkane propellant; and
greater than 5% by weight, based on total weight of the aerosol formulation, of a solvent that is capable of solubilizing or dissolving the &bgr;-agonist drug.
The invention further provides a novel aerosol formulation adapted for use in a pressurized aerosol container, said aerosol formulation being formulated from a composition comprising:
particles of a &bgr;-agonist drug;
at least one fluoroalkane propellant; and
a surfactant that is capable of forming a suspension of the particles of &bgr;-agonist drug.
The aerosol formulations are surprisingly stable under conditions up to about 40° C. and about 75% relative humidity for at least about four weeks.
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Blondino Frank E.
Brucato Michael
Buenafe Maria W.
Baker Norton Pharmaceuticals, Inc.
Bawa Raj
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