Medicinal aerosol products containing formulations of ciclesonide and related steroids

• US 6,120,752 A
• Filed: 05/13/1998
• Issued: 09/19/2000
• Est. Priority Date: 05/21/1997
• Status: Expired due to Term

• Current Assignee: 3M Innovative Properties Company (3M Company), Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: 3M Innovative Properties Company (3M Company), BYK Gulden Lomberg Chemische Fabrik GMBH (Takeda Pharmaceutical Company Limited)
• Inventors: Scott, John S., Oliver, Martin J., Muller, Helgert, Fatania, Kanu M.
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US09/076,958
• Time in Patent Office: 860 Days
• Field of Search: 424/45, 424/46, 514/826
• US Class Current: 424/45
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• 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: A61M 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

A pharmaceutical aerosol formulation suitable for oral and/or nasal inhalation including an anti-inflammatory steroid of the formula ##STR1## in which: R₁ is 1-butyl, 2-butyl, cyclohexyl or phenyl and

R₂ is acetyl or isobutanoyl, in particular ciclesonide. The formulations also include hydrofluorocarbon propellants such as HFC 134a and/or 227, and cosolvent such as ethanol in an amount sufficient to solubilize the ciclesonide or related steroid (and various optional ingredients, such as surfactant). The formulations exhibit very desirable physical and chemical stability, as well as excellent delivery characteristics.

Claims

1. A pharmaceutical aerosol product comprising an aerosol vial equipped with a dispensing valve and containing an aerosol formulation suitable for oral or nasal inhalation comprising a therapeutically effective amount of a dissolved compound of the formula:

##STR4## in which;

R₁ is 1-butyl, 2-butyl, cyclohexyl or phenyl and

R₂ is acetyl or isobutanoyl, and a propellant selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane and a mixture thereof, and cosolvent in an amount effective to solubilize the compound of formula (I) and optionally a surfactant.

2. A pharmaceutical composition as claimed in claim 1 in which the valve is a metered dose dispensing valve.

3. A pharmaceutical composition as claimed in claim 2 in which the valve comprises a valve ferrule having a rim and associated rim gasket for engaging the aerosol vial and an aperture therethrough;

a metering tank having walls defining an exterior, an internal metering chamber, an inlet orifice, an inlet end, and an outlet end;

an elongate valve stem having a filling channel, a filling end, a discharge end, and a discharge orifice;

wherein the outlet end of the metering tank is in sealing engagement with the valve ferrule, the discharge end of the valve stem passes through both the valve ferrule aperture and the outlet end of the metering tank and is in slidable sealing engagement with the valve ferrule;

wherein the filling end of the valve stem passes through and is in slidable engagement with the inlet orifice of the metering tank, and a bottle emptier surrounding the metering tank and filling end of the elongate valve stem and defining a passage between the metering tank and bottle emptier allowing communication between the inlet orifice of the metering tank and the aerosol vial;

wherein the valve stem is movable between an extended closed position wherein the filling channel of the valve stem allows open communication, via the inlet orifice, between the interior and the exterior of the metering chamber, and wherein the outlet end of the metering tank is closed, and a compressed open position wherein the inlet orifice of the metering tank is in sealing engagement with the filling end of the valve stem and the discharge orifice of the valve stem allows open communication between the interior and exterior of the metering chamber.

4. A pharmaceutical product as claimed in claim 3 additionally comprising an adapter having a body for containing the aerosol vial, a nozzle block accommodating the discharge end of the valve stem and a mouthpiece.

5. A pharmaceutical product as claimed in claim 4 in which the nozzle block has an exit orifice directed towards the mouthpiece, the exit orifice having a diameter in the range 0.20 to 0.33 mm.

6. A pharmaceutical product as claimed in claim 5 in which the exit orifice has a diameter of about 0.28 mm.

7. A pharmaceutical product as claimed in claim 6 in which the exit orifice has a jet length in the range 0.30 to 0.60 mm.

8. A pharmaceutical product as claimed in claim 7 in which the exit orifice has a jet length of 0.50 mm.