Compositions, methods and systems for respiratory delivery of two or more active agents

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

COMPOSITIONS, METHODS & SYSTEMS FOR RESPIRATORY DELIVERY OF TWO OR MORE ACTIVE AGENTS

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 161.-. (canceled)62. A pharmaceutical composition deliverable from a metered dose inhaler , the composition comprising:a suspension medium comprising a pharmaceutically acceptable propellant;one or more species of respirable active agent particles comprising two or more active agents; anda plurality of respirable suspending particles different than the active agent particles and comprising a particulate phospholipid material that is substantially insoluble in the suspension medium, wherein the active agent particles and suspending particles are included in the suspension medium at a weight ratio of total mass of the suspending particles to total mass of the one or more species of active agent particles that ranges from above 1:1 and up to 200:1.63. The pharmaceutical composition of claim 62 , wherein the two or more active agents are selected from short-acting beta agonist claim 62 , long-acting and ultra long-acting βadrenergic receptor agonist (LABA) claim 62 , corticosteroid claim 62 , anti-inflammatory claim 62 , anti-tussive claim 62 , bronchodilator claim 62 , muscarinic antagonist claim 62 , and long-acting muscarinic antagonist (LAMA) active agents claim 62 , including any pharmaceutically acceptable salts claim 62 , esters claim 62 , or isomers thereof64. The pharmaceutical composition of claim 63 , wherein the one or more species of respirable active agent particles comprises two or more different species of respirable active agent particles claim 63 , each of the two or more different species of respirable active agent particles comprises a different active agent claim 63 , and the different active ...

Compositions for respiratory delivery of active agents and associated methods and systems

Compositions, methods and systems are provided for pulmonary or nasal delivery of active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Compositions, methods & systems for respiratory delivery of two or more active agents

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

COMPOSITIONS FOR PULMONARY DELIVERY OF LONG-ACTING MUSCARINIC ANTAGONISTS AND ASSOCIATED METHODS AND SYSTEMS

Compositions, methods and systems are provided for pulmonary delivery of long-acting muscarinic antagonists and long-acting β 2 adrenergic receptor agonists via a metered dose inhaler. In particular embodiments, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

COMPOSITIONS FOR RESPIRATORY DELIVERY OF ACTIVE AGENTS AND ASSOCIATED METHODS AND SYSTEMS

Compositions, methods and systems are provided for pulmonary or nasal delivery of active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 1. A pharmaceutical composition deliverable from a metered dose inhaler , comprising:a suspension medium comprising a pharmaceutically acceptable propellant;a first population of particles comprising active agent particles, wherein the active agent particles comprise respirable, micronized active agent; anda second population of particles comprising respirable suspending particles, wherein the respirable suspending particles are substantially insoluble in the suspension medium, and comprise a phospholipid; andwherein a weight ratio of total mass of respirable suspending particles to total mass of active agent particles ranges from 1:1 to about 200:1.2. The pharmaceutical composition according to claim 1 , wherein at least 90% of the active agent particles by volume exhibits an optical diameter of 7 μm or less.3. The pharmaceutical composition according to claim 1 , wherein at least 50% of the active agent particles by volume exhibits an optical diameter of 5 μm or less.4. The pharmaceutical composition according to claim 1 , wherein the active agent particles comprise particles of active agent in crystalline form.57.-. (canceled)8. The pharmaceutical composition according to claim 1 , wherein the active agent particles comprise two or more species of respirable claim 1 , micronized active agent particles.9. The pharmaceutical composition according to claim 1 , wherein the active agent particles comprise one or more active agents selected from short-acting beta agonists claim 1 , such as bitolterol claim 1 , carbuterol claim 1 , fenoterol claim 1 , hexoprenaline claim 1 , isoprenaline (isoproterenol) claim 1 , ...

Compositions for pulmonary delivery of long-acting muscarinic antagonists and associated methods and systems

Compositions, methods and systems are provided for pulmonary delivery of long-acting muscarinic antagonists and long-acting β 2 adrenergic receptor agonists via a metered dose inhaler. In particular embodiments, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

COMPOSITIONS, METHODS & SYSTEMS FOR RESPIRATORY DELIVERY OF TWO OR MORE ACTIVE AGENTS

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 1. A method for treating a pulmonary disease or disorder in a patient , the method comprising: a suspension medium comprising a pharmaceutically acceptable propellant substantially free of additional constituents;', 'a first species of respirable active agent particles comprising a first active agent, wherein the first active agent is substantially crystalline glycopyrrolate, including pharmaceutically acceptable salts, esters, isomers or solvates thereof;', {'sub': '2', 'one or more additional species of respirable active agent particles comprising one or more additional active agents selected from a short-acting beta agonist, a long-acting and ultra long-acting βadrenergic receptor agonist (LABA), a corticosteroid, an anti-inflammatory, an anti-tussive, a bronchodilator, and a muscarinic antagonist; and'}, 'a plurality of respirable suspending particles, wherein the total mass of the respirable suspending particles exceeds the total mass of the respirable active agent particles and the active agent particles associate with the plurality of suspending particles to form a co-suspension; and, 'providing a metered dose inhaler comprising a canister containing a pharmaceutically acceptable co-suspension, the co-suspension comprising{'sub': 1', '1, 'administering the co-suspension to the patient by actuating the metered dose inhaler, wherein said administering of the co-suspension comprises delivering a dose of 150 μg, or less, of glycopyrrolate per actuation of the metered dose inhaler and said delivery results in a clinically significant increase in FEVin 0.5 hours, or less, and the increase in FEVremains ...

COMPOSITIONS, METHODS & SYSTEMS FOR RESPIRATORY DELIVERY OF TWO OR MORE ACTIVE AGENTS

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 130-. (canceled)31. A method for treating a pulmonary disease or disorder in a patient , the method comprising: a suspension medium comprising a pharmaceutically acceptable propellant free of additional constituents;', 'a first species of respirable active agent particles comprising a pharmaceutically acceptable salt, ester, or isomer of glycopyrrolate in crystalline form, as a first active agent;', {'sub': '2', 'one or more additional species of respirable active agent particles comprising one or more additional active agents selected from the group consisting of a short-acting beta agonist, a long-acting and ultra long-acting βadrenergic receptor agonist (LABA), a corticosteroid, an anti-inflammatory, an anti-tussive, a bronchodilator, and a muscarinic antagonist; and'}, 'a plurality of respirable suspending particles, wherein the total mass of the respirable suspending particles exceeds the total mass of the respirable active agent particles, the plurality of suspending particles are formed of a material that is substantially insoluble in the suspension medium, and the active agent particles co-locate with the plurality of suspending particles to form a co-suspension; and, 'providing a metered dose inhaler comprising a canister containing a pharmaceutically acceptable co-suspension, the co-suspension comprisingadministering a therapeutically effective amount of glycopyrrolate and the one or more additional species of active agents to the patient, wherein said administering comprises delivering the co-suspension to the patient by actuating the metered dose inhaler.32. The method of claim 31 , wherein the ...

COMPOSITIONS, METHODS & SYSTEMS FOR RESPIRATORY DELIVERY OF TWO OR MORE ACTIVE AGENTS

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 1. A method for treating a pulmonary disease or disorder in a patient , the method comprising: a suspension medium comprising a pharmaceutically acceptable propellant;', 'two or more active agents;', 'one or more species of respirable active agent particles; and', 'one or more species of respirable suspending particles, wherein the active agent particles and suspending particles associate to form a co-suspension within the suspension medium; and, 'providing a pharmaceutically acceptable co-suspension, the co-suspension comprisingadministering the co-suspension to the patient as a respirable aerosol, wherein said administering of the co-suspension comprises delivering a therapeutically effective amount of the two or more active agents to the patient.2. The method of claim 1 , wherein providing a pharmaceutically acceptable co-suspension comprises providing a co-suspension comprising two or more active agents selected from short-acting beta agonist claim 1 , long-acting and ultra long-acting βadrenergic receptor agonist (LABA) claim 1 , corticosteroid claim 1 , anti-inflammatory claim 1 , anti-tussive claim 1 , bronchodilator claim 1 , muscarinic antagonist claim 1 , and long-acting muscarinic antagonist (LAMA) active agents claim 1 , including any pharmaceutically acceptable salts claim 1 , esters claim 1 , isomers or solvates thereof.3. The method of claim 2 , wherein the pulmonary disease or disorder is selected from at least one of asthma claim 2 , COPD claim 2 , chronic bronchitis claim 2 , emphysema claim 2 , bronchiectasis claim 2 , allergic rhinitis claim 2 , sinusitis claim 2 , pulmonary ...

COMPOSITIONS FOR PULMONARY DELIVERY OF LONG-ACTING B2 ADRENERGIC RECEPTOR AGONISTS AND ASSOCIATED METHODS AND SYSTEMS

Compositions, methods and systems are provided for pulmonary delivery of long-acting muscarinic antagonists and long-acting βadrenergic receptor agonists via a metered dose inhaler. In particular embodiments, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 1. A pharmaceutical composition deliverable from a metered dose inhaler , comprising:a suspension medium comprising a pharmaceutically acceptable propellant;{'sub': '2', 'a plurality of active agent particles comprising an active agent selected from a long-acting muscarinic antagonist (LAMA) active agent and a long-acting βadrenergic receptor agonist (LABA) active agent; and'}a plurality of respirable suspending particles, wherein the plurality of active agent particles associate with the plurality of suspending particles to form a co-suspension.2. A method for treating a pulmonary disease or disorder in a patient , the method comprising: a suspension medium comprising a pharmaceutically acceptable propellant;', 'a plurality of active agent particles comprising an active agent selected from a LAMA active agent and a LABA active agent; and', 'a plurality of respirable suspending particles, wherein the plurality of active agent particles associate with the plurality of suspending particles; and, 'providing metered dose inhaler comprising a pharmaceutically acceptable co-suspension, the co-suspension comprisingadministering the co-suspension to the patient by actuating the metered dose inhaler, wherein said administering of the co-suspension composition comprises delivering a therapeutically effective amount of the LAMA or LABA active agent to the patient.3. A method for respiratory delivery of a LAMA or LABA active agent to a patient , the method comprising; a suspension medium comprising a pharmaceutically acceptable propellant;', 'a plurality of active ...

Compositions for respiratory delivery of active agents and associated methods and systems

Compositions, methods and systems are provided for pulmonary or nasal delivery of active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 154.-. (canceled)55. A pharmaceutical composition deliverable from a metered dose inhaler , the composition comprising:a pharmaceutically acceptable suspension medium;a plurality of active agent particles selected from glycopyrrolate, formoterol and budesonide; anda plurality of suspending particles comprising a phospholipid; wherein the concentration of the suspending particles is between about 1 mg/mL and about 15 mg/mL.56. The pharmaceutical composition of claim 55 , wherein the pharmaceutically acceptable suspension medium is an HFA propellant.57. The pharmaceutical composition of claim 56 , wherein the HFA propellant is HFA-134a.58. The pharmaceutical composition of claim 55 , wherein the amount of glycopyrrolate in the pharmaceutical composition is between about 0.04 mg/mL and about 2.25 mg/mL.59. The pharmaceutical composition of claim 55 , wherein the pharmaceutical composition comprises sufficient glycopyrrolate to provide a delivered dose of up to about 20 μg per actuation of the device.60. The pharmaceutical composition of claim 55 , wherein the glycopyrrolate is 3-[(cyclopentyl-hydroxyphenylacetyloxy]-1 claim 55 ,1-dimethylpyrrolidium bromide.61. The pharmaceutical composition of claim 55 , wherein the amount of formoterol in the pharmaceutical composition is between about 0.01 mg/mL and about 1 mg/mL.62. The pharmaceutical composition of claim 55 , wherein the pharmaceutical composition comprises sufficient formoterol to provide a delivered dose of between about 1 μg and about 30 μg formoterol per actuation of the device.63. The pharmaceutical composition of claim 62 , wherein the pharmaceutical composition ...

COMPOSITIONS FOR PULMONARY DELIVERY OF LONG-ACTING B2 ADRENERGIC RECEPTOR AGONISTS AND ASSOCIATED METHODS AND SYSTEMS

Compositions, methods and systems are provided for pulmonary delivery of long-acting muscarinic antagonists and long-acting βadrenergic receptor agonists via a metered dose inhaler. In particular embodiments, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 154.-. (canceled)55. A pharmaceutical composition deliverable from a metered dose inhaler , comprising:a pharmaceutically acceptable HFA suspension medium;a plurality of respirable suspending particles;a plurality of active agent particles comprising formoterol, or a pharmaceutically acceptable salt thereof, in a concentration of between about 0.01 mg/mL and about 0.5 mg/mL; anda plurality of active agent particles comprising glycopyrrolate, or a pharmaceutically acceptable salt thereof, in a concentration of between about 0.04 mg/mL and about 2.25 mg/mL;wherein the respirable suspending particles are formed separately from the active agent particles and are substantially insoluble in the suspension medium; andwherein the respirable suspending particles are present in the suspension medium at a concentration of between about 5 mg/mL and about 8 mg/mL and at a weight ratio of total mass of the respirable suspending particles to total mass of active agent particles that ranges from 1:1 to 200:1.56. The pharmaceutical composition of claim 55 , wherein the concentration of the formoterol active agents particles is between about 0.03 and about 0.4 mg/mL.57. The pharmaceutical composition of claim 55 , wherein the pharmaceutically acceptable salt of formoterol is formoterol fumarate.58. The pharmaceutical composition of claim 55 , wherein the pharmaceutically acceptable salt of glycopyrrolate is 3-[(cyclopentyl-hydroxyphenylacetyl)oxy]-1 claim 55 ,1-dimethylpyrrolidinium bromide.59. The pharmaceutical composition of claim 55 , wherein the concentration of the ...

COMPOSITIONS FOR RESPIRATORY DELIVERY OF ACTIVE AGENTS AND ASSOCIATED METHODS AND SYSTEMS

Compositions, methods and systems are provided for pulmonary or nasal delivery of active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 154-. (canceled)55. A pharmaceutical composition deliverable from a metered dose inhaler , the composition comprising:a pharmaceutically acceptable suspension medium;a plurality of active agent particles selected from glycopyrrolate, formoterol and budesonide; anda plurality of suspending particles comprising a phospholipid; wherein the concentration of the suspending particles is between about 5 mg/mL and about 8 mg/mL.56. The pharmaceutical composition of claim 55 , wherein the pharmaceutically acceptable suspension medium is an HFA propellant.57. The pharmaceutical composition of claim 56 , wherein the HFA propellant is HFA-134a.58. The pharmaceutical composition of claim 55 , wherein the amount of glycopyrrolate in the pharmaceutical composition is between about 0.04 mg/mL and about 2.25 mg/mL.59. The pharmaceutical composition of claim 55 , wherein the pharmaceutical composition comprises sufficient glycopyrrolate to provide a delivered dose of up to about 20 μg per actuation of the metered dose inhaler.60. The pharmaceutical composition of claim 55 , wherein the glycopyrrolate is 3-[(cyclopentyl-hydroxyphenylacetyloxy]-1 claim 55 ,1-dimethylpyrrolidium bromide.61. The pharmaceutical composition of claim 55 , wherein the amount of formoterol in the pharmaceutical composition is between about 0.01 mg/mL and about 1 mg/mL.62. The pharmaceutical composition of claim 55 , wherein the pharmaceutical composition comprises sufficient formoterol to provide a delivered dose of between about 1 μg and about 30 μg formoterol per actuation of the metered dose inhaler.63. The pharmaceutical composition of claim 62 , wherein the ...

METHODS AND SYSTEMS FOR CONDITIONING OF PARTICULATE CRYSTALLINE MATERIALS

Methods and systems for the preparation of conditioned micronized active agents. Additionally, methods and systems for in-process conditioning of micronized active agent particles and compositions comprising conditioned micronized materials. 1. A method of conditioning a micronized crystalline material comprising:providing aerosolized micronized crystalline particles, wherein said micronized crystalline particles contain one or both of an amorphous material and a residual solvent;continuously mixing the micronized crystalline particles with a conditioning gas comprising a carrier gas and a conditioning vapor in a chamber connected directly to the exit of the micronization apparatus;maintaining the micronized crystalline particles in contact with the conditioning gas for sufficient time to result in annealing of said micronized crystalline particles, wherein said annealing results in one or both of reducing the presence of the amorphous material or reduction in the amount of residual solvent; andseparating the micronized crystalline particles from the conditioning gas.2. The method of claim 1 , wherein the micronized crystalline material is mixed with the conditioning gas for between about 0.1 to 600 seconds before the micronized crystalline material exits the conditioning zone.3. The method of claim 1 , wherein the micronized crystalline material is mixed with the conditioning gas for between about 2 to 6 seconds before the micronized crystalline material exits the conditioning zone.4. The method of claim 2 , wherein the micronized crystalline material is mixed with the conditioning gas for about 3 seconds before the micronized crystalline material exits the conditioning zone.5. The method of claim 1 , wherein the micronized crystalline material is water soluble claim 1 , the solvent vapor included in the conditioning gas is an aqueous solvent vapor claim 1 , and the conditioning gas is provided at a temperature ranging from about 20° C. to 100° C. and at a relative ...

COMPOSITIONS, METHODS AND SYSTEMS FOR RESPIRATORY DELIVERY OF TWO OR MORE ACTIVE AGENTS

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 1. A method for treating a pulmonary disease or disorder in a patient , the method comprising: a suspension medium comprising a pharmaceutically acceptable propellant substantially free of additional constituents;', 'a first species of respirable active agent particles comprising a first active agent, wherein the first active agent is substantially crystalline glycopyrrolate, including pharmaceutically acceptable salts, esters, isomers or solvates thereof;', {'sub': '2', 'one or more additional species of respirable active agent particles comprising one or more additional active agents selected from a short-acting beta agonist, a long-acting and ultra long-acting βadrenergic receptor agonist (LABA), a corticosteroid, an anti-inflammatory, an anti-tussive, a bronchodilator, and a muscarinic antagonist; and'}, 'a plurality of respirable suspending particles, wherein the total mass of the respirable suspending particles exceeds the total mass of the respirable active agent particles and the active agent particles associate with the plurality of suspending particles to form a co-suspension; and, 'providing a metered dose inhaler comprising a canister containing a pharmaceutically acceptable co-suspension, the co-suspension comprising{'sub': 1', '1, 'administering the co-suspension to the patient by actuating the metered dose inhaler, wherein said administering of the co-suspension comprises delivering a dose of 150 μg, or less, of glycopyrrolate per actuation of the metered dose inhaler and said delivery results in a clinically significant increase in FEVin 0.5 hours, or less, and the increase in FEVremains ...

COMPOSITIONS FOR PULMONARY DELIVERY OF LONG-ACTING MUSCARINIC ANTAGONISTS OR LONG-ACTING B2 ADRENERGIC RECEPTOR AGONISTS AND ASSOCIATED METHODS AND SYSTEMS

Compositions, methods and systems are provided for pulmonary delivery of long-acting muscarinic antagonists and long-acting βadrenergic receptor agonists via a metered dose inhaler. In particular embodiments, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 183.-. (canceled)84. A pharmaceutical composition deliverable from a metered dose inhaler , comprising:a suspension medium comprising a pharmaceutically acceptable propellant;{'sub': '2', 'a plurality of active agent particles comprising a long-acting muscarinic antagonist (LAMA) active agent or a long-acting βadrenergic receptor agonist (LABA) active agent; and'}a plurality of respirable suspending particles, wherein the respirable suspending particles are formed separately from and are different particles than the active agent particles and are formed of a dry particulate phospholipid material that is substantially insoluble in the suspension medium;and wherein the ratio of the total mass of the respirable suspending particles to the total mass of the active agent particles is from greater than 1:1 up to 200:1.85. The pharmaceutical composition according to claim 84 , wherein the suspending particles comprise perforated microstructures.86. The pharmaceutical composition according to claim 85 , wherein the perforated microstructures are prepared using a spray drying process.87. The pharmaceutical composition according to claim 86 , wherein the perforated microstructures comprise a spray dried emulsion of perfluorooctyl bromide claim 86 , DSPC claim 86 , and calcium chloride in water.88. The pharmaceutical composition according to claim 84 , wherein the suspending particles exhibit an MMAD selected from the group consisting of between about 10 μm and about 500 nm claim 84 , between about 5 μm and about 750 nm claim 84 , and between about 1 μm and about 3 μm ...

METHODS AND SYSTEMS FOR CONDITIONING OF PARTICULATE CRYSTALLINE MATERIALS

Methods and systems for the preparation of conditioned micronized active agents. Additionally, methods and systems for in-process conditioning of micronized active agent particles and compositions comprising conditioned micronized materials. 1. A method of conditioning a micronized crystalline material comprising:aerosolizing micronized crystalline particles within a delivery gas, wherein said micronized crystalline particles contain one or both of an amorphous material and a residual solvent;continuously mixing the micronized crystalline particles with a conditioning gas comprising a carrier gas and a conditioning vapor in a chamber;maintaining the aerosolized micronized crystalline particles in contact with the conditioning gas for sufficient time to result in annealing of said micronized crystalline particles, wherein said annealing results in one or both of reducing the presence of the amorphous material or reduction in the amount of residual solvent; andseparating the micronized crystalline particles from the conditioning gas.2. The method of claim 1 , wherein the micronized crystalline material is mixed with the conditioning gas for between about 0.1 to 600 seconds before the micronized crystalline material exits the conditioning zone.3. (canceled)4. (canceled)5. The method of claim 1 , wherein the micronized crystalline material is water soluble claim 1 , the solvent vapor included in the conditioning gas is an aqueous solvent vapor claim 1 , and the conditioning gas is provided at a temperature ranging from 20° C. to 100° C. and at a relative humidity ranging from 0.05% to 95%.6. The method of claim 1 , wherein the micronized crystalline material is not water soluble claim 1 , the solvent vapor included in the conditioning gas is an organic solvent vapor claim 1 , and the conditioning gas is provided at a temperature ranging from 20° C. to 100° C. and at a relative saturation of a non-aqueous solvent in the range of 0.05% to 95%.7. The method of claim 1 , ...

COMPOSITIONS, METHODS & SYSTEMS FOR RESPIRATORY DELIVERY OF TWO OR MORE ACTIVE AGENTS

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. 161.-. (canceled)62. A pharmaceutical composition deliverable from a metered dose inhaler , comprising:a pharmaceutically acceptable propellant;a first species of respirable active agent particles comprising glycopyrrolate, or a pharmaceutically acceptable salt thereof;a second species of respirable active agent particles comprising formoterol, or a pharmaceutically acceptable salt thereof;a third species of respirable active agent particles comprising budesonide, or a pharmaceutically acceptable salt thereof; wherein the glycopyrrolate, formoterol and budesonide, or pharmaceutically acceptable salts thereof, are included in the composition in a concentration of between about 0.05 mg/mL and about 5 mg/mL;a plurality of respirable suspending particles comprising 1,2-distearoyl-sn-glycero-3-phosphocholine and calcium chloride in a concentration of between about 3 mg/mL and about 10 mg/mL; and{'sub': '1', 'wherein the pharmaceutical composition provides a clinically significant increase in forced expiratory volume (FEV) upon administration to a subject in need thereof.'}63. The pharmaceutical composition of claim 62 , wherein the glycopyrrolate claim 62 , or a pharmaceutically acceptable salt thereof is present in a concentration of between about 0.04 mg/L and about 2.25 mg/mL.64. The pharmaceutical composition of claim 62 , wherein the glycopyrrolate claim 62 , or a pharmaceutically acceptable salt thereof claim 62 , is present in a concentration sufficient to provide a delivered dose of up to 10 μg upon actuation of the metered dose inhaler.65. The pharmaceutical composition of claim 62 , wherein the ...

METHODS AND SYSTEMS FOR CONDITIONING OF PARTICULATE CRYSTALLINE MATERIALS

Methods and systems for the preparation of conditioned micronized active agents. Additionally, methods and systems for in-process conditioning of micronized active agent particles and compositions comprising conditioned micronized materials. 1. A method of conditioning a micronized crystalline material comprising:aerosolizing micronized crystalline particles within a delivery gas, wherein said micronized crystalline particles contain one or both of an amorphous material and a residual solvent;continuously mixing the micronized crystalline particles with a conditioning gas comprising a carrier gas and a conditioning vapor in a chamber;maintaining the aerosolized micronized crystalline particles in contact with the conditioning gas for sufficient time to result in annealing of said micronized crystalline particles, wherein said annealing results in one or both of reducing the presence of the amorphous material or reduction in the amount of residual solvent; andseparating the micronized crystalline particles from the conditioning gas.2. The method of claim 1 , wherein the micronized crystalline material is mixed with the conditioning gas for between about 0.1 to 600 seconds before the micronized crystalline material exits the conditioning zone.34.-. (canceled)5. The method of claim 1 , wherein the micronized crystalline material is water soluble claim 1 , the solvent vapor included in the conditioning gas is an aqueous solvent vapor claim 1 , and the conditioning gas is provided at a temperature ranging from 20° C. to 100° C. and at a relative humidity ranging from 0.05% to 95%.6. The method of claim 1 , wherein the micronized crystalline material is not water soluble claim 1 , the solvent vapor included in the conditioning gas is an organic solvent vapor claim 1 , and the conditioning gas is provided at a temperature ranging from 20° C. to 100° C. and at a relative saturation of a non-aqueous solvent in the range of 0.05% to 95%.7. The method of claim 1 , wherein the ...

Compositions, methods & systems for respiratory delivery of two or more active agents

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Pharmaceutical formulation comprising a water-insoluble active agent

A method of preparing a pharmaceutical formulation comprises providing a solution comprising a first solvent, a second solvent, an active agent, and an excipient. The second solvent is less polar than the first solvent and the excipient is more soluble in water than the active agent. The first and second solvents are removed from the solution to produce particles comprising the active agent and the excipient. In one version, the excipient comprises an amino acid and/or a phospholipid. A pharmaceutical formulation made by a version of the invention comprises particles comprising an active agent and an excipient which at least partially encapsulates the active agent, wherein the excipient is more soluble in water than the active agent.

Pharmaceutical formulation comprising a water-insoluble active agent

A method of preparing a pharmaceutical formulation comprises providing a solution comprising a first solvent, a second solvent, an active agent, and an excipient. The second solvent is less polar than the first solvent and the excipient is more soluble in water than the active agent. The first and second solvents are removed from the solution to produce particles comprising the active agent and the excipient. In one version, the excipient comprises an amino acid and/or a phospholipid. A pharmaceutical formulation made by a version of the invention comprises particles comprising an active agent and an excipient which at least partially encapsulates the active agent, wherein the excipient is more soluble in water than the active agent.

Spray drying of an alcoholic aqueous solution for the manufacture of a water-in-soluble active agentmicroparticle with a partial or complete amino acid and/or phospholipid coat

Pharmaceutical formulation comprising a water-insoluble active agent

A method of preparing a pharmaceutical formulation comprises providing a solution comprising a first solvent, a second solvent, an active agent, and an excipient. The second solvent is less polar than the first solvent and the excipient is more soluble in water than the active agent. The first and second solvents are removed from the solution to produce particles comprising the active agent and the excipient. In one version, the excipient comprises an amino acid and/or a phospholipid. A pharmaceutical formulation made by a version of the invention comprises particles comprising an active agent and an excipient which at least partially encapsulates the active agent, wherein the excipient is more soluble in water than the active agent.

Composition and method for spray drying an adjuvant vaccine emulsion

The invention provides for thermostable spray dried formulations including vaccines and pharmaceutical compositions for inducing or enhancing an immune response and methods of use thereof. The spray dried formulations are a dry powder generally comprising an antigen and/or an adjuvant, a metabolizable oil, and one or more excipients.

Composition and method for spray drying an adjuvant vaccine emulsion

The invention provides for thermostable spray dried formulations including vaccines and pharmaceutical compositions for inducing or enhancing an immune response and methods of use thereof. The spray dried formulations are a dry powder generally comprising an antigen and/or an adjuvant, a metabolizable oil, and one or more excipients.

Compositions for pulmonary delivery of long-acting muscarinic antagonists and long-acting b2 adrenergic receptor agonists, and associated methods and systems

【課題】定量噴霧式吸入器により活性剤を呼吸器送達するための組成物の提供。【解決手段】薬学的に許容できる噴射剤を含む懸濁媒体と、長時間作用性のムスカリン拮抗剤（ＬＡＭＡ）活性剤および長時間作用性のβ２アドレナリン受容体作動剤（ＬＡＢＡ）活性剤から選択される活性剤を含む複数の活性剤粒子と、複数の呼吸可能な懸濁粒子とを含み、前記複数の活性剤粒子が前記複数の懸濁粒子と会合して共懸濁剤を形成する、医薬組成物。【選択図】図８

Methionine-containing protein or peptide compositions and methods of making and using

Methionine-containing protein or peptide compositions may include at least one methionine-containing protein or peptide and at least one antioxidant that inhibits oxidation of the at least one methionine-containing peptide or protein, wherein the compositions are inhalable. Particles may include a surface enriched with a surface excipient having a glass transition temperature and a core enriched with at least one methionine-containing protein or peptide. Methods of making, methods of treating and unit dosage forms are also included.

Compositions, methods & systems for respiratory delivery of two or more active agents

Abstract of the Disclosure Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and 5 suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Methods and systems for conditioning of particulate crystalline materials

Methods and systems for the preparation of conditioned micronized active agents. Additionally, methods and systems for in-process conditioning of micronized active agent particles and compositions comprising conditioned micronized materials.

Respiratory delivery of active agents

Abstract of the Disclosure Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Spectroscopic determination of soot in the environment

A metal fiber Raman filter and a diode, preferably a wide-band, multimode, i.e. a pump diode, laser are used. Pulsed emission is used to prevent heating of the sample. The wavelength of the laser is to be about 800 nm to limit fluorescence. Normally this kind of laser can be cooled by a Peltier cooler and can be battery driven so that a portable unit can be constructed. In order to prevent the return of stray radiation onto the sample, holographic -, tinted lens -, or interference filters or interference grids are used. Signal quality is improved by amplitude modulation of the laser in combination with lock-in amplification. A CCD array could be used to transform the spectroscopically differentiated radiation into electrical signals. Optical amplifiers could also be used.

Methods and systems for conditioning of particulate crystalline materials

Methods and systems for the preparation of conditioned micronized active agents. Additionally, methods and systems for in-process conditioning of micronized active agent particles and compositions comprising conditioned micronized materials.

Methods and systems for conditioning of particulate crystalline materials

Methods and systems for the preparation of conditioned micronized active agents. Additionally, methods and systems for in-process conditioning of micronized active agent particles and compositions comprising conditioned micronized materials.

Preservation of bioactive materials by freeze dried foam

This invention provides methods, systems and compositions to preserve bioactive materials in a dried foam matrix. Methods provide non-boiling foam generation and penetration of preservative agents at temperatures near the phase transition temperature of the membranes. Bioactive materials can be preserved with high initial viability in a freeze-foam process employing low temperature secondary drying.

Composition and method for spray drying an adjuvant vaccine emulsion

The invention provides for thermostable spray dried formulations including vaccines and pharmaceutical compositions for inducing or enhancing an immune response and methods of use thereof. The spray dried formulations are a dry powder generally comprising an antigen and/or an adjuvant, a metabolizable oil, and one or more excipients.

pharmaceutical composition, methods of treating a disease or disorder, for the respiratory administration of two or more active agents, for the respiratory administration of a combination of active agents, and for preparing a suitable composition.

Compositions for pulmonary delivery of long-acting muscarinic antagonists and long-acting beta-2 adrenergic receptor agonists and associated methods and systems

COMPOSITIONS, PROCEDURES & SYSTEMS FOR AIR ROAD ADMINISTRATION OF TWO OR MORE ACTIVE AGENTS

Compositions for respiratory delivery of active agents and associated methods and systems.

Se proporcionan composiciones, métodos y sistemas para el suministro pulmonar de antagonistas muscarinicos de acción prolongada y agonistas de receptor P2 adrenérgico de acción prolongada a través de un inhalador de dosis mecida. En modalidades particulares, las composiciones incluyen un modo de suspensión, partículas de agente activo y partículas en suspensión en las cuales las partículas de agente activo y las partículas en suspensión forman una co-suspensión dentro del medio de suspensión.

Respiratory delivery of active agents

Compositions for pulmonary delivery of long-acting muscarinic antagonists and long-acting b2 adrenergic receptor agonists and associated methods and systems

Compositions, methods and systems are provided for pulmonary delivery of long-acting muscarinic antagonists and long-acting .beta.2 adrenergic receptor agonists via a metered dose inhaler. In particular embodiments, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Composition and method for spray drying an adjuvant vaccine emulsion

composição e método para secagem por pulverização de uma emulsão de vacina adjuvante. a invenção se refere a formulações secas por pulverização termoestáveis, incluindo vacinas e composições farmacêuticas para induzir ou intensificar uma resposta imune e métodos de uso das mesmas. as formulações secas por pulverização são um pó seco que compreende, geralmente, um antígeno e/ou um adjuvante, um óleo metabolizável e um ou mais excipientes. composition and method for spray drying an adjuvant vaccine emulsion. the invention relates to thermostable spray-dried formulations, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response, and methods of using the same. spray dried formulations are a dry powder which generally comprises an antigen and/or an adjuvant, a metabolizable oil and one or more excipients.

Compositions for pulmonary administration of long-acting muscarinic antagonists and long-acting beta-2 adrenergic receptor agonists and associated methods and systems

Una composicion farmaceutica que puede ser administrada desde un inhalador de dosis medida, que comprende: un medio de suspension que comprende un propulsor farmaceuticamente aceptable; una pluralidad de particulas de agente activo micronizadas que comprende un agente activo seleccionado de glicopirrolato y formoterol, que incluye cualquier sal, ester o solvato farmaceuticamente aceptable de los mismos, en la que al menos el 90% del material particulado del agente activo en volumen exhibe un diametro optico de 7 μm o menos; y una pluralidad de particulas en suspension respirables que comprende microestructuras de fosfolipidos perforadas y que exhibe un diametro optico medio en volumen seleccionado entre 0,2 μm y 50 μm, entre 0,5 μm y 15 μm, entre 1,5 μm y 10 μm, y entre 2 μm y 5 μm; en la que una masa total de particulas en suspension excede una masa total de particulas del agente activo, y la pluralidad de particulas del agente activo se asocia con la pluralidad de particulas en suspension para formar una cosuspension. A pharmaceutical composition that can be administered from a metered dose inhaler, comprising: a suspending medium comprising a pharmaceutically acceptable propellant; a plurality of micronized active agent particles comprising an active agent selected from glycopyrrolate and formoterol, including any pharmaceutically acceptable salt, ester or solvate thereof, wherein at least 90% of the active agent particulate by volume exhibits an optical diameter of 7 µm or less; and a plurality of respirable suspended particles comprising perforated phospholipid microstructures and exhibiting a volume mean optical diameter selected between 0.2 µm and 50 µm, between 0.5 µm and 15 µm, between 1.5 µm and 10 µm. , and between 2 µm and 5 µm; wherein a total mass of suspended particles exceeds a total mass of active agent particles, and the plurality of active agent particles associate with the plurality of suspended particles to form a co-suspension.

Compositions for respiratory delivery of active agents and associated methods and systems

Abstract Compositions, methods and systems are provided for pulmonary or nasal delivery of active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Methods and systems for conditioning of particulate crystalline materials

Methods and systems for the preparation of conditioned micronized active agents. Additionally, methods and systems for in-process conditioning of micronized active agent particles and compositions comprising conditioned micronized materials.

Compositions, methods & systems for respiratory delivery of two or more active agents

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Methods and systems for conditioning of particulate crystalline materials

Compositions for pulmonary delivery of long-acting muscarinic antagonists and long-acting b2 adrenergic receptor agonists and associated methods and systems

Compositions, methods and systems are provided for pulmonary delivery of long-acting muscarinic antagonists and long-acting β 2 adrenergic receptor agonists via a metered dose inhaler. In particular embodiments, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Compositions, methods and systems for respiratory delivery of two or more active agents

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Compositions for pulmonary delivery of long-acting muscarinic antagonists and long-acting B2 adrenergic receptor agonists and associated methods and systems

Compositions, methods and systems are provided for pulmonary delivery of long-acting muscarinic antagonists and long-acting βadrenergic receptor agonists via a metered dose inhaler. In particular embodiments, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Compositions, methods & systems for respiratory delivery of two or more active agents

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Compositions for respiratory delivery of active agents and associated methods and systems

Compositions, methods and systems are provided for pulmonary or nasal delivery of active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Compositions for respiratory delivery of active agents and associated methods and systems

Compositions, methods and systems are provided for pulmonary or nasal delivery of active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

MICRONIZED CRYSTALLINE MATERIAL CONDITIONING METHOD AND CONDITIONING SYSTEMS

MÉTODOS E SISTEMAS PARA CONDICIONAMENTO DE MATERIAIS CRISTALINO S PARTICULADOS Métodos e sistemas para a preparação de agentes ativos micronizados condicionados. Além disso, os métodos e sistemas para o condicionamento durante o processo de partículas de agente ativo micronizado e composições compreendendo materiais micronizados condicionados. METHODS AND SYSTEMS FOR CONDITIONING CRYSTALLINE AND PARTICULATE MATERIALS Methods and systems for preparing micronised conditioned active agents. Further, methods and systems for in-process conditioning of micronized active agent particles and compositions comprising conditioned micronized materials.

Compositions, methods & systems for respiratory delivery of two or more active agents

Compositions, methods and systems are provided for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.

Συνθεσεις, μεθοδοι και συστηματα για τη χορηγηση δυο ή περισσοτερων δραστικων παραγοντων δια της αναπνευστικης οδου

Παρέχονται συνθέσεις, μέθοδοι και συστήματα για την πνευμονική ή τη ρινική χορήγηση δύο ή περισσοτέρων δραστικών παραγόντων, μέσω μίας συσκευής εισπνοής μετρούμενης δόσης. Σε μία υλοποίηση, οι συνθέσεις περιλαμβάνουν ένα μέσο εναιωρήματος, σωματίδια του δραστικού παράγοντα και σωματίδια εναιωρήματος, στα οποία τα σωματίδια του δραστικού παράγοντα και στα σωματίδια εναιωρήματος σχηματίζουν ένα συν-εναιώρημα μέσα στο μέσο εναιωρήματος.

COMPOSICIONES PARA EL SUMINISTRO PULMONAR DE ANTAGONISTAS MUSCARÍNICOS DE ACCIÓN PROLONGADA Y AGONISTAS DEL RECEPTOR ADRENÉRGICO b₂ DE ACCIÓN PROLONGADA, Y MÉTODOS Y SISTEMAS ASOCIADOS

Composiciones, métodos y sistemas para el suministro pulmonar de antagonistas muscarínicos de acción prolongada y agonistas del receptor adrenérgico b₂ de acción prolongada mediante un inhalador dosificador. En formas de realización particulares, las composiciones incluyen un medio de suspensión, partículas de agente activo y partículas en suspensión, en donde las partículas de agente activo y las partículas en suspensión forman una cosuspensión en el medio de suspensión. Reivindicación 1: Una composición farmacéutica que puede suministrarse desde un inhalador dosificador, caracterizada porque comprende: un medio de suspensión que comprende un propulsor farmacéuticamente aceptable; una pluralidad de partículas de agente activo que comprenden un agente activo seleccionado de un agente activo antagonista muscarínico de acción prolongada (LAMA) y un agente activo agonista del receptor adrenérgico b₂ de acción prolongada (LABA); y una pluralidad de partículas en suspensión respirables, en donde la pluralidad de partículas de agente activo se asocian con la pluralidad de partículas en suspensión para formar una cosuspensión. Reivindicación 43: Una composición farmacéutica de acuerdo con la reivindicación 1, caracterizada porque el agente activo incluido en las partículas de agente activo es un agente activo LABA seleccionado de bambuterol, clenbuterol, formoterol, salmeterol, carmoterol, milveterol, indacaterol y agonistas de b₂ derivados de adamantilo y que contienen saligenina o indol, y cualquiera de sus sales, ésteres, isómeros o solvatos farmacéuticamente aceptables.

Composiciones para el suministro de agentes activos mediante las vías respiratorias, y métodos y sistemas asociados

Reivindicación 1: Una cosuspensión que se puede suministrar desde un inhalador dosificador, caracterizada porque la cosuspensión estable comprende: un medio de suspensión que comprende un propulsor farmacéuticamente aceptable; una pluralidad de partículas de agente activo; y una pluralidad de partículas en suspensión respirables, en donde la pluralidad de partículas de agente activo se asocian con la pluralidad de partículas en suspensión a pesar de las diferencias de flotabilidad entre las partículas de agente activo y las partículas en suspensión dentro en el medio de suspensión. Reivindicación 10: Una cosuspensión de acuerdo con cualquiera de las reivindicaciones precedentes, caracterizada porque se incluyen dos o más agentes activos en las partículas de agente activo, y los dos o más agentes activos se seleccionan de una combinación de formoterol y budesonida, una combinación de glicopirrolato y formoterol, una combinación de ciclesonida y formoterol, una combinación de salmeterol y fluticasona, una combinación de glicopirrolato, formoterol y budesonida y una combinación de glicopirrolato, formoterol y mometasona, incluso cualquiera de sus sales, ésteres, isómeros o solvatos farmacéuticamente aceptable. Reivindicación 33: Una cosuspensión de acuerdo con cualquiera de las reivindicaciones precedentes, caracterizada porque las partículas en suspensión comprenden un excipiente seleccionado del grupo que consiste en lípidos, fosfolípidos, detergentes no iónicos, polímeros, tales como copolímeros en bloque no iónicos, tensoactivos, tales como tensoactivos no iónicos y tensoactivos fluorinados biocompatibles, hidratos de carbono, aminoácidos, sales orgánicas, péptidos, proteínas, alditoles y combinaciones de éstos. Reivindicación 36: Una cosuspensión de acuerdo con cualquiera de las reivindicaciones precedentes, caracterizada porque el medio de suspensión comprende propulsor sustancialmente libre de constituyentes adicionales. Reivindicación 37: La cosuspensión de ...

Composición farmacéutica que puede suministrarse desde un inhalador dosificador

Una composición farmacéutica que puede suministrarse desde un inhalador dosificador, que comprende: un medio de suspensión que comprende un propulsor farmacéuticamente aceptable; una pluralidad de partículas de agente activo que comprenden un corticosteroide o una sal farmacéuticamente aceptable del mismo; y una pluralidad de partículas en suspensión respirables que comprenden partículas de fosfolípido tienen una solubilidad menor de una parte por 100 partes de solvente, donde las partículas de fosfolípido comprenden microestructuras perforadas, y la masa total de la pluralidad de partículas en suspensión excede la masa total de las partículas de agente activo. Reivindicación 3: La composición farmacéutica de acuerdo con la reivindicación 1, caracterizada porque el corticosteroide es budesonida. Reivindicación 12: La composición farmacéutica de acuerdo con la reivindicación 11, caracterizada porque el agente activo agonista de beta de corta acción es albuterol.

Compositions for pulmonary delivery of long-acting muscarinic antagonists and long-acting B2 adrenergic receptor agonists and associated methods and systems