Stabilized preparations for use in metered dose inhalers
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-009/00
A61K-009/10
A61K-009/12
A61K-009/14
A61K-038/00
A61K-038/02
A61K-047/42
A61K-031/56
A61K-031/565
A61K-031/567
A61K-031/568
A61K-031/569
A61K-031/57
A61K-031/573
A61K-031/575
A01N-027/00
A01N-029/00
A01N-031/00
A01N-035/00
A01N-033/00
출원번호
UP-0644265
(2003-08-19)
등록번호
US-7628978
(2009-12-16)
발명자
/ 주소
Weers, Jeffry G.
Schutt, Ernest G.
Dellamary, Luis
Tarara, Thomas E.
Kabalnov, Alexey
출원인 / 주소
Novartis Pharma AG
대리인 / 주소
Janah & Associates
인용정보
피인용 횟수 :
14인용 특허 :
331
초록▼
Stabilized dispersions are provided for the delivery of a bioactive agent to the respiratory tract of a patient. The dispersions preferably comprise a plurality of perforated microstructures dispersed in a suspension medium that typically comprises a hydrofluoroalkane propellant. As density variatio
Stabilized dispersions are provided for the delivery of a bioactive agent to the respiratory tract of a patient. The dispersions preferably comprise a plurality of perforated microstructures dispersed in a suspension medium that typically comprises a hydrofluoroalkane propellant. As density variations between the suspended particles and suspension medium are minimized and attractive forces between microstructures are attenuated, the disclosed dispersions are particularly resistant to degradation, such as, by settling or flocculation. In particularly preferred embodiments, the stabilized dispersions may be administered to the lung of a patient using a metered dose inhaler.
대표청구항▼
What is claimed is: 1. A respiratory dispersion for the pulmonary delivery of one or more bioactive agents, the dispersion comprising a suspension medium having dispersed therein a plurality of perforated microstructures, the perforated microstructures comprising at least one bioactive agent wherei
What is claimed is: 1. A respiratory dispersion for the pulmonary delivery of one or more bioactive agents, the dispersion comprising a suspension medium having dispersed therein a plurality of perforated microstructures, the perforated microstructures comprising at least one bioactive agent wherein said suspension medium comprises at least one propellant and permeates said perforated microstructures comprising a mean geometric diameter that is between 0.5 and 5 μm. 2. The respiratory dispersion of claim 1, wherein said propellant comprises a compound selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane, perfluoroethane, monochlorodifluoromethane, 1,1-difluoroethane and combinations thereof. 3. The respiratory dispersion of claim 1 wherein said propellant is a hydrofluoroalkane propellant. 4. The respiratory dispersion of claim 3 wherein said hydrofluoroalkane propellant comprises 1,1,1,2-tetrafluoroethane. 5. The respiratory dispersion of claim 3 wherein said hydrofluoroalkane propellant comprises 1,1,1,2,3,3,3-heptafluoro-n-propane. 6. The respiratory dispersion of claim 1 wherein said perforated microstructures comprise a surfactant. 7. The respiratory dispersion of claim 6 wherein said surfactant is selected from the group consisting of phospholipids, nonionic detergents, nonionic block copolymers, ionic surfactants, biocompatible fluorinated surfactants and combinations thereof. 8. The respiratory dispersion of claim 6 wherein said perforated microstructures comprise oleic acid or its alkali salt. 9. The respiratory dispersion of claim 6 wherein said surfactant comprises a lipid. 10. The respiratory dispersion of claim 9 wherein said lipid has a gel to liquid crystal phase transition greater than about 40° C. 11. The respiratory dispersion of claim 9 wherein said lipid is a phospholipid. 12. The respiratory dispersion of claim 11 wherein said phospholipid is selected from the group consisting of dilauroylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, behenoylphosphatidylcholine, arachidoylphosphatidylcholine and combinations thereof. 13. The respiratory dispersion of claim 6 wherein said perforated microstructures comprise greater than about 10% w/w surfactant. 14. The respiratory dispersion of claim 13 wherein said surfactant comprises a phospholipid. 15. The respiratory dispersion of claim 13 wherein said surfactant comprises oleic acid or its alkali salt. 16. The respiratory dispersion of claim 1 wherein said suspension medium and said perforated microstructures have a refractive index differential of less than about 0.4. 17. The respiratory dispersion of claim 1 wherein said suspension medium and said perforated microstructures have a refractive index differential of less than about 0.3. 18. The respiratory dispersion of claim 1 wherein said perforated microstructures comprise hollow porous microspheres. 19. The respiratory dispersion of claim 18 wherein the perforated microspheres comprise a surfactant. 20. The respiratory dispersion of claim 1 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 5 μm. 21. The respiratory dispersion of claim 1 wherein the perforated microstructures comprise a mean geometric diameter that is between 0.5 and 5 μm. 22. The respiratory dispersion of claim 1 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 3 μm. 23. The respiratory dispersion of claim 1 wherein said perforated microstructures provide a fine particle fraction following aerosolization of greater than 30%. 24. The respiratory dispersion of claim 1 wherein said perforated microstructures provide a fine particle fraction following aerosolization of greater than 50%. 25. The respiratory dispersion of claim 1 wherein the density differential between the density of the suspended perforated microstructures permeated with the suspension medium and the density of the suspension medium is less than about 0.6 g/cm3. 26. The respiratory dispersion of claim 1 wherein said bioactive agent is selected from the group consisting of antiallergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, leukotriene inhibitors or antagonists, antihistamines, antiinflammatories, antiinfectives, antineoplastics, anticholinergics, anesthetics, anti-tuberculars, imaging agents, cardiovascular agents, enzymes, steroids, genetic material, viral vectors, vaccines antisense agents, proteins, peptides and combinations thereof. 27. The respiratory dispersion of claim 1 wherein said bioactive agent is selected from the group consisting of steroids, bronchodilators and peptides. 28. The respiratory dispersion of claim 1 wherein said bioactive agent is selected from the group consisting of budesonide, fluticasone propionate, salmeterol, formoterol and DNase. 29. A respiratory dispersion for the pulmonary delivery of one or more bioactive agents, the dispersion comprising a suspension medium having dispersed therein a plurality of perforated microstructures, the perforated microstructures comprising greater than about 20% w/w surfactant and at least one bioactive agent wherein said suspension medium comprises at least one propellant and permeates the perforated microstructures comprising a mean geometric diameter that is between 0.5 and 5 μm. 30. The respiratory dispersion of claim 29 wherein said dispersed perforated microstructures comprise greater than about 30% w/w surfactant. 31. The respiratory dispersion of claim 29, wherein said propellant comprises a compound selected from the group consisting of 1,1,1,2-tetrafluoroethane 1,1,1,2,3,3,3-heptafluoro-n-propane, perfluoroethane, monochlorodifluoromethane, 1,1-difluoroethane and combinations thereof. 32. The respiratory dispersion of claim 29 wherein said propellant is a hydrofluoroalkane propellant. 33. The respiratory dispersion of claim 32 wherein said hydrofluoroalkane propellant comprises 1,1,1,2-tetrafluoroethane. 34. The respiratory dispersion of claim 29 wherein said surfactant is selected from the group consisting of phospholipids, nonionic detergents, nonionic block copolymers, ionic surfactants, biocompatible fluorinated surfactants and combinations thereof. 35. The respiratory dispersion of claim 29 wherein said perforated microstructures comprise oleic acid or its alkali salt. 36. The respiratory dispersion of claim 29 wherein said surfactant comprises a lipid. 37. The respiratory dispersion of claim 36 wherein said lipid has a gel to liquid crystal phase transition greater than about 40° C. 38. The respiratory dispersion of claim 36 wherein said lipid is a phospholipid. 39. The respiratory dispersion of claim 38 wherein said phospholipid is selected from the group consisting of dilauroylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, behenoylphosphatidylcholine, arachidoylphosphatidylcholine and combinations thereof. 40. The respiratory dispersion of claim 29 wherein said perforated microstructures comprise hollow porous microspheres. 41. The respiratory dispersion of claim 40 wherein said hollow porous microspheres have a mean aerodynamic diameter between about 0.5 to 5 μm. 42. The respiratory dispersion of claim 29 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 5 μm. 43. The respiratory dispersion of claim 29 wherein said bioactive agent is selected from the group consisting of antiallergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, leukotriene inhibitors or antagonists, antihistamines, antiinfectives, antiinflammatories, antineoplastics, anticholinergics, anesthetics, anti-tuberculars, imaging agents, cardiovascular agents, enzymes, steroids, genetic material, viral vectors, vaccines antisense agents, proteins, peptides and combinations thereof. 44. The respiratory dispersion of claim 29 wherein said bioactive agent is selected from the group consisting of budesonide, fluticasone propionate, salmeterol, formoterol and DNase. 45. A respiratory dispersion for the pulmonary delivery of one or more bioactive agents, the dispersion comprising a suspension medium having dispersed therein a plurality of perforated microstructures, the perforated microstructures comprising a structural matrix of phospholipid and at least one bioactive agent, wherein said suspension medium comprises at least one propellant and permeates said perforated microstructures. 46. The respiratory dispersion of claim 45, wherein said propellant comprises a compound selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane, perfluoroethane, monochlorodifluoromethane, 1,1-difluoroethane and combinations thereof. 47. The respiratory dispersion of claim 45 wherein said propellant is a hydrofluoroalkane propellant. 48. The respiratory dispersion of claim 47 wherein said hydrofluoroalkane propellant comprises 1,1,1,2-tetrafluoroethane. 49. The respiratory dispersion of claim 47 wherein said hydrofluoroalkane propellant comprises 1,1,1,2,3,3,3-heptafluoro-n-propane. 50. The respiratory dispersion of claim 45 wherein said perforated microstructures comprise a surfactant. 51. The respiratory dispersion of claim 50 wherein said surfactant is selected from the group consisting of phospholipids, nonionic detergents, nonionic block copolymers, ionic surfactants, biocompatible fluorinated surfactants and combinations thereof. 52. The respiratory dispersion of claim 50 wherein said perforated microstructures comprise oleic acid or its alkali salt. 53. The respiratory dispersion of claim 50 wherein said surfactant comprises a lipid. 54. The respiratory dispersion of claim 45 wherein said phospholipid has a gel to liquid crystal phase transition greater than about 40° C. 55. The respiratory dispersion of claim 45 wherein said phospholipid is selected from the group consisting of dilauroylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, behenoylphosphatidylcholine, arachidoylphosphatidylcholine and combinations thereof. 56. The respiratory dispersion of claim 45 wherein said suspension medium and said perforated microstructures have a refractive index differential of less than about 0.4. 57. The respiratory dispersion of claim 45 wherein said suspension medium and said perforated microstructures have a refractive index differential of less than about 0.3. 58. The respiratory dispersion of claim 45 wherein said perforated microstructures comprise hollow porous microspheres. 59. The respiratory dispersion of claim 45 wherein the perforated microspheres comprise calcium. 60. The respiratory dispersion of claim 45 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 5 μm. 61. The respiratory dispersion of claim 45 wherein the perforated microstructures comprise a mean geometric diameter that is between 0.5 and 5 μm. 62. The respiratory dispersion of claim 45 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 3 μm. 63. The respiratory dispersion of claim 45 wherein said perforated microstructures provide a fine particle fraction following aerosolization of greater than 30%. 64. The respiratory dispersion of claim 45 wherein the density differential between the density of the suspended perforated microstructures permeated with the suspension medium and the density of the suspension medium is less than about 0.6 g/cm3". 65. The respiratory dispersion of claim 45 wherein said bioactive agent is selected from the group consisting of antiallergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, leukotriene inhibitors or antagonists, antihistamines, antiinfectives, antiinflammatories, antineoplastics, anticholinergics, anesthetics, anti-tuberculars, imaging agents, cardiovascular agents, enzymes, steroids, genetic material, viral vectors, vaccines antisense agents, proteins, peptides and combinations thereof. 66. The respiratory dispersion of claim 45 wherein said bioactive agent is selected from the group consisting of steroids, bronchodilators and peptides. 67. The respiratory dispersion of claim 45 wherein said bioactive agent is selected from the group consisting of budesonide, fluticasone propionate, salmeterol, formoterol and DNase. 68. A respiratory dispersion for the pulmonary delivery of one or more bioactive agents, the dispersion comprising a suspension medium having dispersed therein a plurality of perforated microstructures, the perforated microstructures comprising a structural matrix of phospholipid, calcium, and at least one bioactive agent, wherein said suspension medium comprises at least one propellant and permeates said perforated microstructures. 69. The respiratory dispersion of claim 68 wherein said propellant comprises a compound selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane, perfluoroethane, monochlorodifluoromethane, 1,1-difluoroethane and combinations thereof. 70. The respiratory dispersion of claim 68 wherein said propellant is a hydrofluoroalkane propellant. 71. The respiratory dispersion of claim 70 wherein said hydrofluoroalkane propellant comprises 1,1,1,2-tetrafluoroethane. 72. The respiratory dispersion of claim 70 wherein said hydrofluoroalkane propellant comprises 1,1,1,2,3,3,3-heptafluoro-n-propane. 73. The respiratory dispersion of claim 68 wherein said perforated microstructures comprise a surfactant. 74. The respiratory dispersion of claim 73 wherein said surfactant is selected from the group consisting of phospholipids, nonionic detergents, nonionic block copolymers, ionic surfactants, biocompatible fluorinated surfactants and combinations thereof. 75. The respiratory dispersion of claim 73 wherein said perforated microstructures comprise oleic acid or its alkali salt. 76. The respiratory dispersion of claim 73 wherein said surfactant comprises a lipid. 77. The respiratory dispersion of claim 68 wherein said phospholipid has a gel to liquid crystal phase transition greater than about 40° C. 78. The respiratory dispersion of claim 68 wherein said phospholipid is selected from the group consisting of dilauroylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, behenoylphosphatidylcholine, arachidoylphosphatidylcholine and combinations thereof. 79. The respiratory dispersion of claim 68 wherein said suspension medium and said perforated microstructures have a refractive index differential of less than about 0.4. 80. The respiratory dispersion of claim 68 wherein said suspension medium and said perforated microstructures have a refractive index differential of less than about 0.3. 81. The respiratory dispersion of claim 68 wherein said perforated microstructures comprise hollow porous microspheres. 82. The respiratory dispersion of claim 68 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 5 μm. 83. The respiratory dispersion of claim 68 wherein the perforated microstructures comprise a mean geometric diameter that is between 0.5 and 5 μm. 84. The respiratory dispersion of claim 68 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 3 μm. 85. The respiratory dispersion of claim 68 wherein said bioactive agent has a fine particle fraction following aerosolization of greater than 30%. 86. The respiratory dispersion of claim 68 wherein the density differential between the density of the suspended perforated microstructures permeated with the suspension medium and the density of the suspension medium is less than about 0.6 g/cm3". 87. The respiratory dispersion of claim 68 wherein said bioactive agent is selected from the group consisting of antiallergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, leukotriene inhibitors or antagonists, antihistamines, antiinfectives, antiinflammatories, antineoplastics, anticholinergics, anesthetics, anti-tuberculars, imaging agents, cardiovascular agents, enzymes, steroids, genetic material, viral vectors, vaccines antisense agents, proteins, peptides and combinations thereof. 88. The respiratory dispersion of claim 68 wherein said bioactive agent is selected from the group consisting of steroids, bronchodilators and peptides. 89. The respiratory dispersion of claim 68 wherein said bioactive agent is selected from the group consisting of budesonide, fluticasone propionate, salmeterol, formoterol and DNase. 90. A respiratory dispersion for the pulmonary delivery of one or more bioactive agents, the dispersion comprising a suspension medium having dispersed therein a plurality of perforated microstructures, the suspension medium comprising at least one propellant that permeates said perforated microstructures, and the perforated microstructures comprising at least one bioactive agent in a structural matrix comprising at least one phospholipid selected from the group consisting of dilauroylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, behenoylphosphatidylcholine, arachidoylphosphatidylcholine and combinations thereof. 91. The respiratory dispersion of claim 90 wherein the perforated microspheres comprise calcium. 92. The respiratory dispersion of claim 90 wherein the perforated microspheres comprise magnesium. 93. The respiratory dispersion of claim 90 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 5 μm. 94. The respiratory dispersion of claim 90 wherein the perforated microstructures comprise a mean geometric diameter that is between 0.5 and 5 μm. 95. The respiratory dispersion of claim 90 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 3 μm. 96. A respiratory dispersion for the pulmonary delivery of one or more bioactive agents, the dispersion comprising a suspension medium having dispersed therein a plurality of perforated microstructures, the suspension medium comprising at least one propellant that permeates said perforated microstructures, and the perforated microstructures comprising: a structural matrix comprising at least one phospholipid selected from the group consisting of dilauroylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, behenoylphosphatidylcholine, arachidoylphosphatidylcholine and combinations thereof; and at least one bioactive agent selected from the group consisting of antiallergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, leukotriene inhibitors or antagonists, antihistamines, antiinfectives, antiinflammatories, antineoplastics, anticholinergics, anesthetics, anti-tuberculars, imaging agents, cardiovascular agents, enzymes, steroids, genetic material, viral vectors, vaccines antisense agents, proteins, peptides and combinations thereof. 97. The respiratory dispersion of claim 96 wherein the perforated microspheres comprise calcium. 98. The respiratory dispersion of claim 96 wherein the perforated microspheres comprise magnesium. 99. The respiratory dispersion of claim 96 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 5 μm. 100. The respiratory dispersion of claim 96 wherein the perforated microstructures comprise a mean geometric diameter that is between 0.5 and 5 μm. 101. The respiratory dispersion of claim 96 wherein the perforated microstructures comprise a mean geometric diameter that is between 1 and 3 μm.
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Bodner Mordechai (San Diego CA) De Polo Nicholas J. (Solana Beach CA) Chang Stephen (Poway CA) Hsu David Chi-Tang (San Diego CA) Respess James G. (San Diego CA), Retroviral delivery of full length factor VIII.
Knight Jack V. (Houston TX) Gilbert Brian E. (Houston TX) Wilson Samuel Z. (Houston TX) Six Howard R. (East Stroudsborg PA) Wyde Philip R. (Houston TX), Small particle aerosol liposome and liposome-drug combinations for medical use.
Roser, Bruce J.; Colaco, Camilo; Jerrow, Mohammed A. Z.; Blair, Julian; Kampinga, Jaap; Wardell, James Lewis; Duffy, John Alistair, Solid delivery systems for controlled release of molecules incorporated therein and methods of making same.
Manning Mark C. ; Randolph Theodore W. ; Shefter Eli ; Falk ; III Richard F., Solubilization of pharmaceutical substances in an organic solvent and preparation of pharmaceutical powders using the s.
Sutton Andrew D.,GBX ; Johnson Richard A.,GBX ; Senior Peter J.,GBX ; Heath David,GBX, Spray-dried microparticles and their use as therapeutic vehicles.
Schneider Michel (Troinex CHX) Bichon Daniel (Montpellier FRX) Bussat Philippe (Collonge S/Saleve FRX) Puginier Jerome (Le Chable-Beaumont FRX) Hybl-Sutherland Eva (Wiesbaden DEX), Stable microbubbles suspensions injectable into living organisms.
Goldin Stanley M. (Lexington MA) Katragadda Subbarao (Belmont MA) Hu Lain-Yen (Bedford MA) Reddy N. Laxma (Malden MA) Fischer James B. (Cambridge MA) Knapp Andrew G. (Salem MA) Margolin Lee D. (Belmo, Substituted guanidines and derivatives thereof as modulators of neurotransmitter release and novel methodology for ident.
Wong Sui-Ming (Collegeville PA) Newington Ian M. (Hazlemere GB2) Liversidge Elaine M. (West Chester PA) McIntire Gregory L. (West Chester PA) Pitt Alan R. (Sandridge GBX) Shaw Jack M. (Aberdeen MD), Sulfated nonionic block copolymer surfactants as stabilizer coatings for nanoparticle compositions.
Liversidge Gary G. (West Chester PA) Conzentino ; Jr. Philip (West Chester PA) Cundy Kenneth C. (Pottstown PA) Sarpotdar Pramod P. (Malvern PA), Surface modified NSAID nanoparticles.
Liversidge Gary G. (West Chester PA) Cundy Kenneth C. (Pottstown PA) Bishop John F. (Rochester NY) Czekai David A. (Honeoye Falls NY), Surface modified drug nanoparticles.
Andersson Jan (Sodra Sandby SEX) Jagfeldt Hans (Lund SEX) Trofast Eva (Lund SEX) Wetterlin Kjell (Sodra Sandby SEX), System for dispensing pharmaceutically active compounds.
Backstrom Kjell Goran Erik,SEX ; Dahlback Carl Magnus Olof,SEX ; Edman Peter,SEX ; Johansson Ann Charlotte Birgit,SEX, Systemic administration of a therapeutic preparation.
Bckstrm Kjell G. E. (Lund SEX) Dahlbck Carl M. O. (Lund SEX) Edman Peter (Bjrred SEX) Johansson Ann C. B. (Lund SEX), Systemic administration of a therapeutic preparation.
Unger Evan C. (Tucson AZ) Fritz Thomas A. (Tucson AZ) Matsunaga Terry (Tucson AZ) Ramaswami VaradaRajan (Tucson AZ) Yellowhair David (Tucson AZ) Wu Guanli (Tucson AZ), Therapeutic delivery systems related applications.
Unger Evan C. (Tucson AZ) Fritz Thomas A. (Tucson AZ) Matsunaga Terry (Tucson AZ) Ramaswami VaradaRajan (Tucson AZ) Yellowhair David (Tucson AZ) Wu Guanli (Tucson AZ), Therapeutic drug delivery systems.
Backstrom Kjell Goran Erik,SEX ; Dahlback Carl Magnus Olof,SEX ; Edman Peter,SEX ; Johansson Ann Charlotte Birgit,SEX, Therapeutic preparation for inhalation.
Bckstrm Kjell G. E. (Lund SEX) Dahlbck Carl M. O. (Lund SEX) Edman Peter (Bjrred SEX) Johansson Ann C. B. (Lund SEX), Therapeutic preparation for inhalation.
Berger Jacob (Los Altos Hills) Clark Robin D. (Palo Alto) Eglen Richard M. (Mountain View) Smith William L. (Sunnyvale) Weinhardt Klaus K. (San Francisco CA), Tricyclic 5-HT3receptor antagonists.
Schultz Robert K. (Shoreview MN) Quessy Stephen N. (St. Paul MN), Use of soluble fluorosurfactants for the preparation of metered-dose aerosol formulations.
Vehring, Reinhard; Hartman, Michael Steven; Smith, Adrian Edward; Joshi, Vidya B.; Dwivedi, Sarvajna Kumar, Compositions for pulmonary delivery of long-acting muscarinic antagonists and associated methods and systems.
Vehring, Reinhard; Hartman, Michael Steven; Smith, Adrian Edward; Joshi, Vidya B.; Dwivedi, Sarvajna Kumar, Compositions for pulmonary delivery of long-acting β2 adrenergic receptor agonists and associated methods and systems.
Vehring, Reinhard; Hartman, Michael Steven; Lechuga-Ballesteros, David; Smith, Adrian Edward; Joshi, Vidya B.; Dwivedi, Sarvajna Jumar, Compositions, methods and propellant-based systems for respiratory delivery of glycopyrrolate and one or more active agents.
Vehring, Reinhard; Hartman, Michael Steven; Lechuga-Ballesteros, David; Smith, Adrian Edward; Joshi, Vidya B.; Dwivedi, Sarvajna Kumar, Compositions, methods and systems for respiratory delivery of two or more active agents.
Vehring, Reinhard; Hartman, Michael Steven; Lechuga-Ballesteros, David; Smith, Adrian Edward; Joshi, Vidya B.; Dwivedi, Sarvajna Kumar, Compositions, methods and systems for respiratory delivery of two or more active agents.
Vehring, Reinhard; Hartman, Michael Steven; Lechuga-Ballesteros, David; Smith, Adrian Edward; Joshi, Vidya B.; Dwivedi, Sarvajna Kumar, Compositions, methods and systems for respiratory delivery of two or more active agents.
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