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Assignees
Member
Kindeva Drug DeliveryKindeva Drug Delivery is a contract development and manufacturing organization specializing in advanced drug delivery systems including pulmonary, nasal, injectable, transdermal, and intradermal therapies. Services range from formulation and analytical development to commercial-scale, Annex 1-compliant GMP manufacturing across global facilities. The company brings integrated expertise in regulatory strategy, device engineering, process and technology transfer, and quality assurance, with a focus on sustainable solutions such as low-GWP propellants and microneedle patch platforms. Kindeva supports complex, patient-centric, and environmentally optimized therapies from product conception through commercialization.
Kindeva Drug Delivery is a contract development and manufacturing organization specializing in advanced drug delivery systems including pulmonary, nasal, injectable, transdermal, and intradermal therapies. Services range from formulation and analytical development to commercial-scale, Annex 1-compliant GMP manufacturing across global facilities. The company brings integrated expertise in regulatory strategy, device engineering, process and technology transfer, and quality assurance, with a focus on sustainable solutions such as low-GWP propellants and microneedle patch platforms. Kindeva supports complex, patient-centric, and environmentally optimized therapies from product conception through commercialization.
Publication Number
US-12220525-B2
Publication Date
2025-02-11
Expiration Date
Abstract
A metered dose inhaler equipped with a metering valve and having an aerosol canister containing a pharmaceutical composition comprising propellant, ethanol, citric acid, and tiotropium or a pharmaceutically acceptable salt or solvate thereof dissolved in the composition, wherein the aerosol canister has an internal surface that is a non-metal material that is in contact with the pharmaceutical composition.
Core Innovation
The invention relates to a stable, water-free pharmaceutical composition for use in a metered dose inhaler. The metered dose inhaler includes a metering valve and an aerosol canister that contains a composition comprising propellant, ethanol at no greater than about 20 wt. %, citric acid at no greater than 0.07 wt. %, and tiotropium or a pharmaceutically acceptable salt or solvate thereof dissolved in the composition. The pharmaceutical composition does not include water, and the aerosol canister has an internal surface of a non-metal material that is in contact with the pharmaceutical composition.
The disclosure addresses stability and compatibility of tiotropium in the presence of propellant and excipients, and identifies incompatibility with HFA-227 that prevents formation of a stable solution. The composition is described as predominantly based on HFA-134a, and includes citric acid and ethanol within the stated concentration limits. The tiotropium is provided as dissolved tiotropium, including tiotropium bromide, supporting stability over storage in the water-free formulation.
Compatibility is further supported by non-metal coatings on the aerosol canister internal surface. The internal surface is described as having non-metal coatings such as silane primer plus fluorinated compounds, including at least partially fluorinated compounds disposed on the coating composition. Additional non-metal coating options described include polyphenylsulphone and diamond-like glass or carbon-like glass, including implementation on the metering valve interior.
Claims Coverage
The document provides two independent claims and key refinements. The claims center on the combination of a water-free tiotropium-containing composition with defined ethanol and citric acid limits, an aerosol canister having a non-metal internal surface contacting the composition, and a metered dose inhaler configuration including a metering valve.
Water-free metered dose inhaler composition with tiotropium dissolved in propellant
A metered dose inhaler equipped with a metering valve and an aerosol canister containing a pharmaceutical composition comprising propellant; ethanol at a concentration of no greater than about 20 wt. %; citric acid at a concentration of no greater than 0.07 wt. %; and tiotropium or a pharmaceutically acceptable salt or solvate thereof dissolved in the composition, wherein the pharmaceutical composition does not include water.
Non-metal aerosol canister internal surface contacting the pharmaceutical composition
An aerosol canister of the metered dose inhaler having an internal surface that is a non-metal material that is in contact with the pharmaceutical composition.
Metered dose inhaler pharmaceutical composition consisting of water-free components with quantitative limits
A metered dose inhaler equipped with a metering valve and having an aerosol canister containing a pharmaceutical composition consisting of propellant; ethanol at a concentration of no greater than about 20 wt. %; citric acid at a concentration of no greater than 0.07 wt. %; and tiotropium or a pharmaceutically acceptable salt or solvate thereof dissolved in the composition, wherein the aerosol canister has an internal surface that is a non-metal material that is in contact with the pharmaceutical composition.
Propellant comprising specified fluorinated hydrocarbons
The metered dose inhaler wherein the propellant comprises one or more specified fluorinated hydrocarbons including 1,1-difluoroethane, 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane, or combinations thereof.
Non-metal surface chemistry using silane primer plus fluorinated compound
The metered dose inhaler wherein the non-metal material is a silane primer composition with multiple reactive silane groups linked by an organic linker, and wherein a coating composition having at least partially fluorinated compound is disposed on the silane primer.
Storage stability defined by tiotropium loss threshold
The metered dose inhaler wherein losing less than 5 wt. % of tiotropium content after six months of storage in an aerosol canister at 25°C and 60% relative humidity.
Across the independent claims and refinements, the claimed inventive concept is a water-free tiotropium-dissolved metered dose inhaler composition with ethanol and citric acid within the stated limits, used in an aerosol canister having a non-metal internal surface in contact with the composition; further refinements specify fluorinated hydrocarbon propellants, non-metal coating chemistry using silane primer plus at least partially fluorinated compounds, and a defined storage stability threshold based on tiotropium loss.
Stated Advantages
Improved stability/compatibility for dissolved tiotropium in the water-free metered dose inhaler formulation using a non-metal internal surface and specified non-metal coatings.
Defined storage stability performance, including losing less than 5 wt. % of tiotropium content after six months under specified temperature and relative humidity.
Maintained aerosol performance characterized by aerodynamic particle size distribution (NGI) and uniformity of delivered dose (UoDD) as described in the document.
Documented Applications
Metered dose inhaler use for a pharmaceutical composition comprising tiotropium or a pharmaceutically acceptable salt or solvate thereof dissolved in a propellant system with ethanol and citric acid, with a non-metal aerosol canister internal surface.
Performance and stability evaluation use cases including aerodynamic particle size distribution testing (NGI), uniformity of delivered dose (UoDD), and tiotropium stability over storage.
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