WO1992022286A1 - Formulations pour aerosol en suspension comprenant du sulfate d'albuterol - Google Patents
Formulations pour aerosol en suspension comprenant du sulfate d'albuterol Download PDFInfo
- Publication number
- WO1992022286A1 WO1992022286A1 PCT/US1992/004587 US9204587W WO9222286A1 WO 1992022286 A1 WO1992022286 A1 WO 1992022286A1 US 9204587 W US9204587 W US 9204587W WO 9222286 A1 WO9222286 A1 WO 9222286A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- weight
- percent
- albuterol sulfate
- aerosol
- ethanol
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
Definitions
- This invention relates to suspension aerosol formulations suitable for the administration of medicaments.
- it relates to pharmaceutical suspension aerosol formulations containing albuterol sulfate and in yet another aspect to aerosol formulations using 1,1,1,2-tetrafluoroethane as the propellant.
- Albuterol sulfate is a relatively selective beta 2 -adrenergic bronchodilator. It is available in a variety of different dosage forms including tablets, syrups and formulations suitable for inhalation.
- VENTOLIN 1 " Inhalation Aerosol (commercially available from Allen & Hansburys, Division of Glaxo Inc.; Research Triangle Park, NC) is a metered-dose aerosol unit containing a microcrystalline suspension of albuterol (free base) in propellant (a mixture of trichloromonofluoromethane and dichlorodifluoromethane) with oleic acid.
- VENTOLIN ROTOCAPSTM for Inhalation (commercially available from Allen & Hansburys) contain a mixture of microfine albuterol sulfate with lactose and are intended for use with a specially designed device for inhaling powder.
- VENTOLINTM Solution for Inhalation (commercially available from Allen & Hansburys) is an aqueous solution of albuterol sulfate intended for use with a nebulizer.
- Chlorofluorocarbons including dichloromonofluoro ⁇ methane and dichlorodifluoromethane, have been implicated in the destruction of the ozone layer and their production is being phased out.
- Hydrofluorocarbon 134a (1,1,1,2-tetrafluoroethane) is viewed as being less destructive to ozone than many chlorofluorocarbon propellents; furthermore, it has a low toxicity and a vapor pressure that is suitable for use in aerosols.
- This invention provides suspension aerosol formulations comprising about 0.05 to about 1.5 percent by weight micronized albuterol sulfate, about 0.25 to about 2 percent by weight of oleic acid, about 5 to about 20 percent by weight ethanol, and 1,1,1,2-tetrafluoroethane. This invention also provides a method for inducing bronchodilation in a mammal.
- suspension aerosol formulations of the invention are suitable for oral inhalation.
- suspension aerosol means that the albuterol sulfate is in powder form and is substantially insoluble in the propellant/ethanol blend.
- micronized means that the albuterol sulfate is in the form of a fine powder, that is, over 90 percent of the particles will have a diameter of less than about 10 microns. All weight percentages recited herein are based on the total weight of the formulation unless otherwise indicated.
- Micronized albuterol sulfate constitutes from about 0.05 to 1.5 percent by weight, preferably from about 0.05 to about 1.3 percent by weight, more preferably about 0.4 to about 0.8 percent by weight, and most preferably about 0.4 to about 0.5 percent by weight of the aerosol formulation.
- Oleic acid constitutes from about 0.25 to about 2 percent by weight, preferably from about 0.25 to about 1.0 percent by weight, more preferably about 0.25 to about 0.75 percent by weight, and most preferably about 0.5 percent by weight of the aerosol formulation.
- Ethanol constitutes from about 5 to about 20 percent by weight, preferably about 12 to about 17 percent by weight, and most preferably about 15 percent by weight of the aerosol formulation.
- the aerosol formulations of this invention do not contain a propellant other than 1,1,1,2-tetrafluoroethane.
- the aerosol formulations of the present invention do not contain ingredients other than
- 1,1,1,2-tetrafluoroethane 1,1,1,2-tetrafluoroethane, ethanol, oleic acid, and albuterol sulfate.
- a particularly preferred formulation according to the invention comprises, in addition to
- the suspension aerosol formulations of this invention can be prepared by first preparing a solution of oleic acid and ethanol in 1,1,1,2-tetrafluoroethane and then suspending the albuterol sulfate in the solution. In order to prepare, a formulation in this manner, the oleic acid and ethanol are placed in an aerosol vial, then 1,1,1,2-tetrafluoroethane is added. The vial is then sealed with a continuous valve.
- the micronized albuterol sulfate is placed in a separate aerosol vial, a continuous valve is crimped onto the vial and the vial is pressure filled with the previously prepared solution.
- the albuterol sulfate is then dispersed in the solution by mixing or homogenizing.
- the formulations can be prepared by first placing the micronized albuterol sulfate, the oleic acid and ethanol in an aerosol vial. In order to prepare a formulation in this manner, a continuous valve is crimped onto a vial containing the micronized albuterol sulfate, the oleic acid, and the ethanol.
- the vial is then pressure filled with 1,1,1,2-tetrafluoroethane and shaken to disperse the albuterol sulfate.
- Preferred formulations of this invention exhibit substantially no growth in particle size or change in crystal morphology of albuterol sulfate over a prolonged period, are substantially and readily redispersible, and upon redispersion do not flocculate so quickly as to prevent reproducible dosing of albuterol sulfate.
- Particle Size Assay metered dose(s) of the aerosol formulation are actuated into filtered Propellant 113 using a needle fitted for an aerosol valve. The particle size distribution of the resulting suspension is then analyzed using a laser diffraction particle size analyzer.
- the particle sizer used is a Malvern 2600c
- the suspending liquid is filtered Propellant 113.
- the aerosol vial to be tested is shaken and primed five times into a vented area away from the analyzer and the suspending liquid.
- the inside of the valve stem, the needle, and the adapter are then flushed with methanol or isopropanol followed by a flush with filtered Propellant 113. All parts are then thoroughly dried with pressurized air.
- the aerosol vial is fitted into the needle, the end of the needle is submerged into the sample cell, and the aerosol vial is actuated. Actuation is repeated (if necessary) until the obscuration value is in the range of 0.15 to 0.30.
- the sample is then analyzed and the percent of particles under 3.0 microns, 5.0 microns and 10.5 microns is reported for each sample.
- the respirable fraction (the percent of particles having an aerodynamic particle size of less than 4.7 microns) of the aerosol suspension is determined using an Anderson Cascade Impactor (available from Anderson Sampler Inc. ; Atlanta, GA) .
- the aerosol vial to be tested is primed five times.
- the valve and valve stem are then cleaned with methanol and dried with compressed air.
- the aerosol vial and a clean, dry actuator are coupled to the glass throat attached to the top of the impactor using an appropriate firing adapter.
- the calibrated vacuum pump (28.3 L/min) attached to the cascade impactor is turned on. A total of 20 sprays is delivered into the cascade impactor by repeatedly shaking the vial, seating it in the actuator and then immediately delivering a single spray.
- the time between sprays is approximately 30 seconds.
- the cascade impactor is disassembled and each component is rinsed separately with diluent (45 parts of methanol mixed with 55 parts 0.1% phosphoric acid, v/v) .
- diluent 45 parts of methanol mixed with 55 parts 0.1% phosphoric acid, v/v
- Each solution is analyzed for albuterol sulfate content using high pressure liquid chromatography.
- the respirable fraction is calculated as follows:
- % respirable drug recovered from plates 3-7 X 100 total drug - drug recovered from recovered actuator and valve Medication Delivery Assay This assay measures the amount of albuterol sulfate delivered per shot.
- sample diluent prepared by mixing 45 parts of methanol with 55 parts of 0.1% phosphoric acid, v/v
- USP XXI Artificial Respiratory System
- the aerosol vial and actuator are coupled to the intake tube of the Artificial Respiratory System (ARS) using an appropriate firing adapter.
- a total of 4 sprays is delivered into the ARS by repeatedly shaking the vial, seating it in the actuator, applying vacuum (12 ⁇ 1 liter per minute) and immediately delivering a single spray.
- the vial is separated from the actuator after each spray.
- the aerosol vial, actuator and firing adapter are uncoupled from the intake tube.
- the gas washing bottle, firing adapter and intake tube are rinsed with diluent.
- the rinses are combined with the diluent originally placed in the gas wash bottle and analyzed for albuterol sulfate content using high pressure liquid chromatography.
- Example 1 A 0.25 g portion of oleic acid was placed in a 4 ounce vial, 5.0 g of ethanol was added and then 94.25 g of cold (about -65°C) 1,1,1,2-tetrafluoroethane was added. A continuous valve was sealed onto the vial immediately after the addition of the 1,1,1,2-tetrafluoroethane. The resulting stock solution contained 0.25% by weight of oleic acid and 5.0 % by weight of ethanol. A 100 mg portion of micronized albuterol sulfate was placed in each of four 15 mL glass aerosol vials along with 5 mL of glass beads. The vials were sealed with continuous valves and then charged with approximately 20 g of the stock solution.
- the vials were shaken on a WIG-L-BUGTM mixer for at least 30 seconds.
- the resulting aerosol suspension formulations contained 0.5% by weight of albuterol sulfate.
- the vials were chilled in dry ice, the valves were removed and the vial contents were transferred to four 15 mL aluminum vials.
- the vials were sealed with 25 microliter SpraymiserTM (available from Neotechnic; Clithroe, UK) valves. Using the test method described above, the respirable fraction was determined in duplicate. Values of 52.7% and 51.6% were obtained.
- aerosol suspension formulations containing 0.5% by weight of oleic acid, 15.0% by weight of ethanol and 0.5% by weight of albuterol sulfate were prepared.
- the respirable fraction was determined in duplicate. Values of 26.3% and 23.1% were obtained.
- Table 1 shows the amount (percent by weight based on the total weight of the formulation) of oleic acid and ethanol used.
- a 0.1 g portion of micronized albuterol sulfate was added to each of three 15 mL glass aerosol vials containing 5 mL portions of glass beads. Oleic acid and ethanol were added to the vials which were then immediately sealed with continuous valves.
- 1,1,1,2-tetrafluoroethane was added through the valve by using a pressure buret.
- the vials were then shaken on a WIG-L-BUGTM mixer for at least 30 seconds.
- the resulting suspensions were transferred to 15 mL aluminum aerosol vials and sealed with 25 microliter SpraymiserTM valves.
- the respirable fractions were determined in duplicate using the test method described above. The values obtained are shown in Table 1.
- Example 3-5 Using the general method of Examples 3-5, a series of suspension aerosol formulations containing 1.0% by weight of oleic acid and 0.5% by weight of micronized albuterol sulfate were prepared. Table 2 shows the amount (percent by weight based on the total weight of the formulation) of ethanol contained in each formulation. After the formulations had been maintained at room temperature for 42 days, the particle size of the albuterol sulfate was determined using the assay described above. The vials were then placed in a cycling (the temperature is cycled from 4°C to 40°C every 6 hours) chamber. Particle size analysis was performed after 15 days and 22 days. The results of the particle size assays are shown in Table 2. The percent of particles under 3.0 microns, 5.0 microns and 10.5 microns is shown. TABLE 2
- Examples 11-13 Using the general method of Examples 3-5, a series of suspension aerosol formulations containing 0.5% by weight of oleic acid and 15.0% by weight of ethanol were prepared. Table 3 shows the amount (percent by weight based on the total weight of the formulation) of albuterol sulfate contained in each formulation. The respirable fractions were determined in duplicate using the test method described above. The values obtained are shown in Table 3.
- Table 4 shows the amount (percent by weight based on the total weight of the formulation) of ethanol and micronized albuterol sulfate contained in each formulation. These formulations were tested for their ability to deliver a consistent dose throughout the "life" of the aerosol by determining the amount of albuterol sulfate delivered per shot for shots 1-4, 96-100, 196-200, 296-300 and 396-400. The amount delivered per shot was determined using the assay described below. The results are shown in Table 4.
- a firing disk was placed in a 100 mL beaker and submerged in about 30 mL of diluent (55 parts 0.1% phosphoric acid/45 parts methanol) .
- the vial was shaken, inserted into the firing disk, and actuated. This step was repeated until a total of 4 actuations had been made.
- the valve and valve stem were rinsed into the beaker with additional diluent.
- the solution in the beaker was quantitatively transferred to a 100 mL volumetric flask which was then brought to volume with additional diluent.
- the vial was then dried and weighed. The amount of albuterol sulfate in the solution was then determined using high performance liquid chromatography.
- the appropriate number of shots were fired (similar to priming) .
- the valve stem was cleaned and dried, and the vial was weighed. The assay was then repeated.
- a 8.0 g portion of albuterol sulfate and a 10.0 g portion of oleic acid were placed in a 150 mL beaker.
- a portion of ethanol was added and the mixture was stirred for at least 3 minutes.
- the resulting slurry was passed through a pump homogenizing system then collected in a tared beaker. Enough ethanol was added to the beaker to bring the total weight of the concentrate (albuterol sulfate, oleic acid, ethanol) to 318 g.
- the concentrate was chilled then placed along with 1682 g of chilled 1,1,1,2-tetrafluoroethane into a cold filling system which had been prechilled to about -40°C.
- Aerosol vials were filled with 14.0 ⁇ 0.5 g of formulation then sealed with 25 ⁇ L SpraymiserTM valves. The resulting formulation contained 0.4% by weight albuterol sulfate.
- the Medication Delivery Assay, described above was performed on two vials. Values of 98.9 ⁇ g albuterol sulfate per shot and 98.7 ⁇ g albuterol sulfate per shot were obtained. Using the assay described above, the respirable fraction was determined using 8 different vials. Values of 54.9%, 53.7%, 55.7%, 58.0%, 52.8%, 51.9%, 56.0%, and 56.0% were obtained.
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Abstract
Formulations d'aérosol en suspension comprenant du sulfate d'albutérol, de l'acide oléique, de l'éthanol et du tétrafluoroéthane-1,1,1,2.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US71379391A | 1991-06-12 | 1991-06-12 | |
US713,793 | 1991-06-12 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1992022286A1 true WO1992022286A1 (fr) | 1992-12-23 |
Family
ID=24867564
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1992/004587 WO1992022286A1 (fr) | 1991-06-12 | 1992-06-02 | Formulations pour aerosol en suspension comprenant du sulfate d'albuterol |
Country Status (6)
Country | Link |
---|---|
AU (1) | AU2178392A (fr) |
IE (1) | IE921851A1 (fr) |
IL (1) | IL102141A0 (fr) |
MX (1) | MX9202855A (fr) |
WO (1) | WO1992022286A1 (fr) |
ZA (1) | ZA924206B (fr) |
Cited By (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU709052B2 (en) * | 1991-12-18 | 1999-08-19 | Minnesota Mining And Manufacturing Company | Suspension aerosol formulations |
US6004537A (en) * | 1998-12-18 | 1999-12-21 | Baker Norton Pharmaceuticals, Inc. | Pharmaceutical solution aerosol formulations containing fluoroalkanes, budesonide and formoterol |
US6054488A (en) * | 1996-06-11 | 2000-04-25 | 3M Innovative Properties Company | Medicinal aerosol formulations of formoterol |
US6290930B1 (en) | 1998-12-18 | 2001-09-18 | Baker Norton Pharmaceuticals, Inc. | Pharmaceutical solution aerosol formulations containing fluoroalkanes and budesonide |
US6451285B2 (en) | 1998-06-19 | 2002-09-17 | Baker Norton Pharmaceuticals, Inc. | Suspension aerosol formulations containing formoterol fumarate and a fluoroalkane propellant |
WO2005003090A1 (fr) | 2003-06-13 | 2005-01-13 | Theravance, Inc. | Derives de 1-(alkylaminoalkyl-pyrolidin-/piperidinyl)-2,2-diphenylacetamide utilises comme antagonistes du recepteur muscarinique |
US7101534B1 (en) | 1991-12-18 | 2006-09-05 | 3M Innovative Properties Company | Suspension aerosol formulations |
WO2007090822A2 (fr) * | 2006-02-09 | 2007-08-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Formulation pharmaceutique destinée à des aérosols, contenant au moins deux agents actifs et au moins une substance tensioactive |
EP1930323A1 (fr) | 2004-03-11 | 2008-06-11 | Theravance, Inc. | Composés biphényle convenant pour la préparation d'antagonistes du récepteur muscarinique |
US7566445B1 (en) | 1996-08-01 | 2009-07-28 | Norton Healthcare Limited | Medicinal aerosols and methods of delivery thereof |
EP2246345A1 (fr) | 2003-02-14 | 2010-11-03 | Theravance Inc | Derives de type biphenyle ayant une activite comme agonistes de recepteurs beta 2 adrenergiques et comme antagonistes de recepteurs muscariniques |
WO2011008809A1 (fr) | 2009-07-15 | 2011-01-20 | Theravance, Inc. | Formes à base libre cristalline d'un composé biphenyle |
WO2012027693A2 (fr) | 2010-08-27 | 2012-03-01 | Neonc Technologies Inc. | Compositions pharmaceutiques comprenant des dérivés de l'alcool périllylique (poh) |
US8236862B2 (en) | 2009-02-06 | 2012-08-07 | University Of Southern California | Therapeutic compositions comprising monoterpenes |
WO2014140647A1 (fr) | 2013-03-15 | 2014-09-18 | Verona Pharma Plc | Association de médicaments |
US9211269B2 (en) | 2010-12-17 | 2015-12-15 | Neonc Technologies Inc. | Methods and devices for using isoperillyl alcohol |
WO2015199626A1 (fr) * | 2014-06-27 | 2015-12-30 | World Medicine İlaç Sanayi̇ Ve Ti̇caret Anoni̇m Şi̇rketi̇ | Formulations stables d'aérosol d'agonistes β2-adrénergiques |
WO2016115147A1 (fr) | 2015-01-13 | 2016-07-21 | Neonc Technologies Inc. | Compositions pharmaceutiques contenant des dérivés de poh |
US9545487B2 (en) | 2012-04-13 | 2017-01-17 | Boehringer Ingelheim International Gmbh | Dispenser with encoding means |
US9616060B2 (en) | 2002-04-17 | 2017-04-11 | Nektar Therapeutics | Particulate materials |
US9682202B2 (en) | 2009-05-18 | 2017-06-20 | Boehringer Ingelheim International Gmbh | Adapter, inhalation device, and atomizer |
US9724482B2 (en) | 2009-11-25 | 2017-08-08 | Boehringer Ingelheim International Gmbh | Nebulizer |
US9744313B2 (en) | 2013-08-09 | 2017-08-29 | Boehringer Ingelheim International Gmbh | Nebulizer |
US9757750B2 (en) | 2011-04-01 | 2017-09-12 | Boehringer Ingelheim International Gmbh | Medicinal device with container |
US9827384B2 (en) | 2011-05-23 | 2017-11-28 | Boehringer Ingelheim International Gmbh | Nebulizer |
US9833451B2 (en) | 2007-02-11 | 2017-12-05 | Map Pharmaceuticals, Inc. | Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile |
US9943654B2 (en) | 2010-06-24 | 2018-04-17 | Boehringer Ingelheim International Gmbh | Nebulizer |
WO2018102412A1 (fr) | 2016-11-30 | 2018-06-07 | Neonc Technologies, Inc. | Conjugué d'alcool périllylique-3-bromopyruvate et méthodes de traitement de cancer |
US10004857B2 (en) | 2013-08-09 | 2018-06-26 | Boehringer Ingelheim International Gmbh | Nebulizer |
US10011906B2 (en) | 2009-03-31 | 2018-07-03 | Beohringer Ingelheim International Gmbh | Method for coating a surface of a component |
US10016568B2 (en) | 2009-11-25 | 2018-07-10 | Boehringer Ingelheim International Gmbh | Nebulizer |
US10099022B2 (en) | 2014-05-07 | 2018-10-16 | Boehringer Ingelheim International Gmbh | Nebulizer |
US10124129B2 (en) | 2008-01-02 | 2018-11-13 | Boehringer Ingelheim International Gmbh | Dispensing device, storage device and method for dispensing a formulation |
US10124125B2 (en) | 2009-11-25 | 2018-11-13 | Boehringer Ingelheim International Gmbh | Nebulizer |
US10195374B2 (en) | 2014-05-07 | 2019-02-05 | Boehringer Ingelheim International Gmbh | Container, nebulizer and use |
WO2019157195A1 (fr) | 2018-02-08 | 2019-08-15 | Neonc Technologies, Inc | Procédés de perméabilisation de la barrière hémato-encéphalique |
CN110585177A (zh) * | 2019-10-17 | 2019-12-20 | 广东同德药业有限公司 | 硫酸沙丁胺醇吸入气雾剂及其制备工艺 |
US10722666B2 (en) | 2014-05-07 | 2020-07-28 | Boehringer Ingelheim International Gmbh | Nebulizer with axially movable and lockable container and indicator |
WO2020182322A1 (fr) | 2019-03-14 | 2020-09-17 | Om Pharma Sa | Méthode de traitement et/ou de prévention de l'asthme, d'exacerbations de l'asthme, de l'asthme allergique et/ou d'états associés à un microbiote lié à des troubles respiratoires |
US10864213B2 (en) | 2014-05-12 | 2020-12-15 | Verona Pharma Plc | Treatment |
EP3769754A1 (fr) | 2010-03-03 | 2021-01-27 | Neonc Technologies, Inc. | Compositions pharmaceutiques comprenant des monoterpènes |
EP3872069A1 (fr) | 2015-02-12 | 2021-09-01 | Neonc Technologies, Inc. | Compositions pharmaceutiques comprenant des dérivés d'alcool périllylique |
Citations (1)
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EP0372777B1 (fr) * | 1988-12-06 | 1993-01-07 | Riker Laboratories, Inc. | Formulations d'aérosols à usage médical |
-
1992
- 1992-06-02 AU AU21783/92A patent/AU2178392A/en not_active Abandoned
- 1992-06-02 WO PCT/US1992/004587 patent/WO1992022286A1/fr active Application Filing
- 1992-06-09 IL IL102141A patent/IL102141A0/xx unknown
- 1992-06-09 ZA ZA924206A patent/ZA924206B/xx unknown
- 1992-06-12 MX MX9202855A patent/MX9202855A/es unknown
- 1992-07-01 IE IE185192A patent/IE921851A1/en not_active Application Discontinuation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0372777B1 (fr) * | 1988-12-06 | 1993-01-07 | Riker Laboratories, Inc. | Formulations d'aérosols à usage médical |
Cited By (65)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU709052C (en) * | 1991-12-18 | 2002-04-11 | Minnesota Mining And Manufacturing Company | Suspension aerosol formulations |
AU709052B2 (en) * | 1991-12-18 | 1999-08-19 | Minnesota Mining And Manufacturing Company | Suspension aerosol formulations |
US7101534B1 (en) | 1991-12-18 | 2006-09-05 | 3M Innovative Properties Company | Suspension aerosol formulations |
US6054488A (en) * | 1996-06-11 | 2000-04-25 | 3M Innovative Properties Company | Medicinal aerosol formulations of formoterol |
US9650203B2 (en) | 1996-08-01 | 2017-05-16 | Norton Healthcare Limited | Medicinal aerosols and methods of delivery thereof |
US8834849B2 (en) | 1996-08-01 | 2014-09-16 | Norton Healthcare Limited | Medicinal aerosols and methods of delivery thereof |
US7566445B1 (en) | 1996-08-01 | 2009-07-28 | Norton Healthcare Limited | Medicinal aerosols and methods of delivery thereof |
US6451285B2 (en) | 1998-06-19 | 2002-09-17 | Baker Norton Pharmaceuticals, Inc. | Suspension aerosol formulations containing formoterol fumarate and a fluoroalkane propellant |
US6290930B1 (en) | 1998-12-18 | 2001-09-18 | Baker Norton Pharmaceuticals, Inc. | Pharmaceutical solution aerosol formulations containing fluoroalkanes and budesonide |
US6004537A (en) * | 1998-12-18 | 1999-12-21 | Baker Norton Pharmaceuticals, Inc. | Pharmaceutical solution aerosol formulations containing fluoroalkanes, budesonide and formoterol |
US9616060B2 (en) | 2002-04-17 | 2017-04-11 | Nektar Therapeutics | Particulate materials |
US10251881B2 (en) | 2002-04-17 | 2019-04-09 | Nektar Therapeutics | Particulate materials |
EP3012254A1 (fr) | 2003-02-14 | 2016-04-27 | Theravance Respiratory Company, LLC | Dérivé de type biphényle et son utilisation pour le traitement de troubles pulmonaires |
EP2246345A1 (fr) | 2003-02-14 | 2010-11-03 | Theravance Inc | Derives de type biphenyle ayant une activite comme agonistes de recepteurs beta 2 adrenergiques et comme antagonistes de recepteurs muscariniques |
WO2005003090A1 (fr) | 2003-06-13 | 2005-01-13 | Theravance, Inc. | Derives de 1-(alkylaminoalkyl-pyrolidin-/piperidinyl)-2,2-diphenylacetamide utilises comme antagonistes du recepteur muscarinique |
EP1930323A1 (fr) | 2004-03-11 | 2008-06-11 | Theravance, Inc. | Composés biphényle convenant pour la préparation d'antagonistes du récepteur muscarinique |
EA014776B1 (ru) * | 2006-02-09 | 2011-02-28 | Бёрингер Ингельхайм Фарма Гмбх Унд Ко. Кг | Фармацевтическая композиция для аэрозольного распыления с двумя действующими веществами и по меньшей мере одним поверхностно-активным веществом |
WO2007090822A3 (fr) * | 2006-02-09 | 2007-11-08 | Boehringer Ingelheim Pharma | Formulation pharmaceutique destinée à des aérosols, contenant au moins deux agents actifs et au moins une substance tensioactive |
WO2007090822A2 (fr) * | 2006-02-09 | 2007-08-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Formulation pharmaceutique destinée à des aérosols, contenant au moins deux agents actifs et au moins une substance tensioactive |
US10172853B2 (en) | 2007-02-11 | 2019-01-08 | Map Pharmaceuticals, Inc. | Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile |
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Publication number | Publication date |
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IL102141A0 (en) | 1993-01-14 |
ZA924206B (en) | 1993-03-31 |
MX9202855A (es) | 1992-12-01 |
IE921851A1 (en) | 1992-12-16 |
AU2178392A (en) | 1993-01-12 |
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