WO1999018971A1 - Mometasone furoate suspensions for nebulization - Google Patents
Mometasone furoate suspensions for nebulization Download PDFInfo
- Publication number
- WO1999018971A1 WO1999018971A1 PCT/US1998/020480 US9820480W WO9918971A1 WO 1999018971 A1 WO1999018971 A1 WO 1999018971A1 US 9820480 W US9820480 W US 9820480W WO 9918971 A1 WO9918971 A1 WO 9918971A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- suspension
- mometasone furoate
- buffer
- surfactant
- solid particles
- 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
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
Definitions
- the present invention relates to aqueous suspensions of water- insoluble pharmaceutical substances, and more particularly to suspensions of substances intended for inhalation therapy.
- inhaled therapeutic substances has become common for the treatment of airway disorders, such disorders including, without limitation thereto, asthma, infections, emphysema and various inflammatory conditions.
- Substances commonly delivered to the lower airway surfaces, that is, the trachea, bronchial tree and lungs, by oral or nasal inhalation include bronchodilators, corticosteroids, anti-infectives and anti-inflammatory medicaments.
- Various methods have been used for such delivery, including pressurized metered dose inhalers, dry powder inhalers and nebulizers. Nebulizers are considered to be instruments generating very fine particles of a liquid in a gas.
- particles intended for treatment of the lower airway i.e., the bronchial tree or the lungs
- particles much smaller than about 0.5 ⁇ m in the largest dimension frequently are not easily deposited at the desired location, and a large fraction of these simply will be exhaled by a patient.
- it is generally desired to produce particles which average 1-7 ⁇ m in their largest dimension while preferably minimizing production of particles having sizes either less than about 0.5 or greater than about 10 ⁇ m.
- the more preferred average particle sizes are in the range of 0.5-5 ⁇ m.
- Nebulization although used more infrequently than other drug delivery techniques, has certain advantages for special patient groups, such as young children and the very infirm. Although somewhat cumbersome equipment is needed and there may be more stringent cleaning requirements than exist for some of the more popular delivery techniques, no particular patient skill or coordination is required: the patient merely needs to breathe normally to introduce the medication into the airway. Thus, treatment can be delivered even to an unconscious patient or an infant. It is also considered an advantage of nebulizers that quantities of moisture are delivered to the airway; this may help to fluidize secretions and tends to increase patient comfort.
- the typical nebulized medication is a water-soluble substance which can form relatively dilute aqueous solutions. This is desired, due to the relatively large volumes of solution which will be entrained in an inhaled air stream, and to the very small quantities of drug which will typically be delivered in a single treatment. Handling of a drug solution is quite uncomplicated: a desired volume of a solution (usually aqueous) is either nebulized directly or is measured into a larger volume of sterile water for nebulization.
- inhalation drugs have little or essentially no water solubility.
- examples of such drugs are corticosteroids, typically administered in the treatment of asthma by inhalation from pressurized metered dose inhalers, either in alcohol solution or as suspended micronized particles, or from dry powder inhalers of various types.
- corticosteroid mometasone furoate for treating disorders of the lower airway make this drug a desirable candidate for delivery by nebulization. Since this drug is not soluble in aqueous media, it has become necessary to develop aqueous suspensions for nebulization.
- the invention comprises an aqueous suspension of micronized mometasone furoate monohydrate, also containing a nonionic surfactant, a soluble salt and optionally a pH buffer.
- a nonionic surfactant are those known as polysorbates.
- the soluble salt may be sodium chloride, in amounts needed to render the solution phase isotonic.
- the buffer When the buffer is present, it preferably will be chosen to maintain a solution pH between about 3 and about 7.
- Fig. 1 is a graphical representation of results from the experiment of Example 3.
- the suspension formulations of the invention may be delivered to a patient using any of the usual nebulizer devices.
- Typical commercial nebulizer devices produce dispersions of droplets in gas streams by one of two methods. Jet nebulizers use a compressed air supply to draw up a fluid by venturi action and introduce it into a flowing gas stream, after which the fluid is caused to impact one or more stationary baffles to remove excessively large droplets.
- Jet nebulizers use an electrically driven transducer to subject a fluid to high-frequency oscillations, producing a cloud of droplets which can be entrained in a moving gas stream; these devices are less preferred for delivering suspensions.
- Suspension formulations suitable for nebulization must, of course, contain solid particles of a respirable size (e.g., preferably averaging less than about 5 ⁇ m in the largest dimension and more preferably averaging less than about 2 ⁇ m) and must maintain their suspended particle size distribution during storage.
- the particle-containing droplets formed during nebulization of the formulations must have appropriate sizes for deposition in the desired area of the respiratory system.
- the formulations of the invention are to be inhaled, it is necessary that they be free of pathogenic organisms. Thus, they may be prepared and handled under sterile conditions, or may be sterilized before or after packaging. In addition, or in lieu of sterilization, a preservative may be incorporated to minimize the possibility of microbial contamination. In addition, all components of the formulations must be chosen for inhalation safety, as the treated tissues are quite sensitive to irritants; it is commonly known that many of the common preservatives have a considerable potential for causing irritation.
- the inventive formulations comprise water, mometasone furoate monohydrate, a nonionic surfactant, a soluble salt and optionally a pH buffer.
- Water for use in the formulations should meet or exceed the applicable regulatory requirements for use in inhaled drugs. Specifications established by the United States Pharmacopoeia for "Sterile Water for Injection” or “Sterile Water for Inhalation” are examples of water suitable for use to prepare formulations of the invention.
- Mometasone furoate is a corticosteroid having the chemical name 9 ⁇ ,21-Dichloro-11 ⁇ ,17-dihydroxy-16 ⁇ -methylpregna-1 ,4-diene-3,20-dione 17- (2-furoate), and is currently marketed by Schering Corporation in cream and lotion formulations for the treatment of dermatologic conditions.
- Information concerning the preparation and properties of mometasone furoate is given in United States Patent 4,472,393. This compound may be used to prepare mometasone furoate monohydrate for use in the present invention.
- Information concerning the preparation and properties of mometasone furoate monohydrate is given in PCT International Application WO 92/04365.
- the concentration of mometasone furoate included in the suspension formulation will depend upon the dose to be delivered to the patient, ease of handling and the characteristics of the nebulizer equipment, as the devices vary considerably in their suspension capacities and nebulization efficiencies.
- Typical suspensions may contain as much as about 5 mg/mL of mometasone furoate, although lower concentrations, such as 50 ⁇ g/mL to 1 mg/mL are more customary for most equipment.
- Surfactants are frequently categorized by their chemical nature, i.e., as cationic, anionic or nonionic.
- Cationic surfactants such as cetyl pyridinium chloride
- anionic surfactants such as docusate sodium, do not appear to provide proper dispersions of particles in the formulations.
- nonionic surfactants are suitable for maintaining the particulate suspensions of the invention. These include surfactants identified as "polysorbates” in the CTFA International Cosmetic Ingredient Dictionary; such surfactants are mixtures of fatty acid esters (predominately monoesters) of sorbitol and sorbitol anhydrides, condensed with ethylene oxide. Although these surfactants vary widely in their hydrophilic-lipophilic balance (“HLB”) numbers, they all appear to function well in the invention. -o-
- polysorbates which are useful in the invention include those listed in the following table, which shows the CTFA designation (Polysorbate number), identity of the fatty acid used to produce the material and the number of moles of ethylene oxide reacted with each mole of ester. Compositions identified with an asterisk are predominately triesters.
- Polysorbate surfactants will be present in a formulation at about 50 to 500 ⁇ g/mL. When the surfactant concentration is below about 20 ⁇ g/mL, the particles tend to form cakes which are not easily redispersed.
- Useful surfactants also include the "Poloxamers,” which are block polymers of polyoxyethylene and polyoxypropylene, generally corresponding to the following formula:
- Poloxamer surfactants are used at concentrations similar to those for the Polysorbates, although certain members are useful at concentrations up to about 1 mg/mL.
- the chosen surfactant should not materially increase the viscosity of the suspension formulation, since the efficiency of the nebulization process is particularly sensitive to viscosity.
- Many nonionic surfactants are useful for preparing inhalation and/or injectable drug formulations, and any of these should be suitable for use in the present invention.
- the formulations further include a soluble salt.
- This salt performs at least two functions: it minimizes the effects of the inhaled formulation on the normal cell fluid balance of airway cells and also stabilizes the suspension of medicament.
- For the first function it is preferred to use sufficient salt concentrations to render the formulation isotonic; sodium chloride and potassium chloride are preferred for this purpose. It has been found that adequate suspension stability is produced by isotonic concentrations (i.e., about 0.9 weight percent) of sodium chloride, although concentrations about 0.2 to about 2 weight percent are useful. Any physiologically compatible alkali metal or alkaline earth metal soluble salt can be used in the present invention.
- the formulations will contain a pH buffer, to maintain the formulation pH between about 3 and about 7. It has been found that stability of the drug (as measured by the absence of degradation reaction products) in suspension is improved by maintaining pH conditions below about 6. For reasons of tissue compatibility, excessively acidic products are not desired, so the pH should not be made to be below about 3. Some experimentation may be needed to qualify specific buffers for use in the invention: phosphate buffers in concentrations of 1 to 50 millimolar do not appear to adequately prevent caking of the particulates in the suspension when there is no added soluble salt..
- a citrate-citric acid buffer, maintaining pH between about 4 and about 5, has been used with particularly good effect for both maintaining pH during storage and preventing any particulate caking in the absence of soluble salts.
- the citrate-citric acid buffer may be present in suspension formulations at concentrations at least about 2 and up to about 50 millimolar. While the literature has some reports of cough being induced by such buffer systems, this seems to occur primarily at the 150-200 millimolar level, although one report attributed cough to only a 35 millimolar concentration.
- Sterility or adequate antimicrobial preservation of the final packaged formulation is needed for patient protection.
- the use of antimicrobial preservatives is less desirable, since certain of these have been associated with adverse clinical effects, such as bronchospasm.
- Alternative processes which may be considered for achieving sterility usually will not include sterilization steps for the micronized drug substance or formulation, since it has been found that the drug undergoes degradation under the influence of gamma-ray irradiation and sterilizing heat conditions. Sterilization by filtration ordinarily will not be feasible, due to the suspension nature of the formulation.
- it is preferred to produce the mometasone furoate monohydrate under sterile conditions conduct the drug micronization in a sterile environment, and perform a sterile packaging operation.
- Suspensions of drug particles can rapidly undergo particulate size reduction when subjected to "jet milling” (high pressure particle in liquid milling) techniques.
- a presently preferred jet milling procedure for producing the formulations of the invention involves the use of the "Microfluidizer” system sold by Microfluidics International Corporation of Newton, Massachusetts, U.S.A. This device divides a fluid stream, flowing under high pressures (up to about 40,000 pounds per square inch, or 2.76 x 10 8 newton/meter 2 ), between two separate microchannel paths and then recombines them from generally perpendicular directions to create very high shear, impact and cavitation forces.
- Sterile mometasone furoate monohydrate is prepared by a procedure including the following steps:
- a sterilizing filter such as a filtration medium having pores not exceeding 0.2 ⁇ m in diameter
- a sterile precipitation vessel equipped with means for stirring and means for heating the contents (note that sterile equipment and a sterile environment must be used for all subsequent steps);
- the dried sterile mometasone furoate monohydrate product should have a water content, as measured by a standard Karl Fischer titration, of 3.3 percent by weight and contains 96.7 percent by weight mometasone furoate.
- a 40 liter batch of a sterile aqueous suspension of mometasone furoate monohydrate is prepared using the following procedure:
- step (1) add 21.73 grams of mometasone furoate monohydrate, prepared as in Example 1 , to the sterile solution of step (1) and commence stirring the vessel contents to form a suspension; (4) pass the mixture of the preceding step through a sterilized Model 210B-EH pilot-scale Microfluidizer operating at 17500 ⁇ 500 pounds per square inch (1.21 x 10 8 newton/meter 2 ⁇ 3.45 x 10 6 newton/meter 2 ) gauge pressure for 40 + 5 minutes while returning the Microfluidizer discharge into the stirred recirculation vessel ;
- the weight for the mometasone furoate monohydrate includes a 5 percent overcharge to compensate for manufacturing losses.
- a suspension which has the following composition and a pH about 4.5:
- a particle size distribution is determined for the suspension by a laser light scattering technique.
- a Malvern 2600 instrument manufactured by Maivern Instruments, Malvern, Worcestershire, United Kingdom, is set up with a liquid flow cell and a 63 mm lens, and operated in its "particle in liquid” mode with water (containing a small amount of Polysorbate 80 as a wetting agent) as the vehicle.
- Drug suspension is added until an optimum light obscuration is achieved, then the measurements are obtained.
- Data are calculated and expressed on a volume distribution basis, and are graphically represented as shown in Fig. 1. This suspension has a median particle size of 1.24 ⁇ m and a mean particle size of 1.34 ⁇ m.
- nebulizers are used to determine the drug delivery characteristics for the suspension of the preceding example and two commercial suspension products: BECOTIDE beclomethasone dipropionate suspension (Glaxo) and PULMICORT budesonide suspension (Astra).
- the nebulizers are WHISPER JET (Marquest Medical Products, Englewood, Colorado, U.S.A.) and PARI JET (PARI Respiratory Equipment, Inc., Richmond, Virginia, U.S.A.). Suspensions are placed into the nebulizers in 3 mL amounts, and the equipment is connected to a compressor and operated according to the manufacturers' instructions.
- Nebulized drug is directed into the top of a 500 mL separatory funnel containing a 1 gram plug of cotton, and the lower outlet of the funnel is connected to a vacuum line. After the nebulizer becomes dry, the vacuum line is disconnected and the funnel (with the plug) is washed with 25 mL of a solvent for the drug (e.g., methanol), which is then collected and analyzed for the drug by high performance liquid chromatography to determine the percentage of originally charged drug which was delivered to the funnel. Results are obtained as follows, where the values are averages of four determinations: Percent Delivered
- Citric acid monohydrate ⁇ g 181 181 80
- the mometasone furoate content is provided by mometasone furoate monohydrate.
- Mometasone furoate ⁇ g 500 500 750
- Citric acid monohydrate ⁇ g 294 181 181 Sodium Citrate dihydrate, ⁇ g 174 335 335 Sodium chloride, mg 9 4.5 18
- the mometasone furoate content is provided by mometasone furoate monohydrate.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Cosmetics (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000515604A JP3676674B2 (en) | 1997-10-09 | 1998-10-06 | Mometasone furoate suspension for spraying |
AT98950781T ATE216244T1 (en) | 1997-10-09 | 1998-10-06 | MOMETASONE FUROATE SUSPENSIONS FOR ABRASION |
DE69804998T DE69804998T2 (en) | 1997-10-09 | 1998-10-06 | MOMETASON FUROAT SUSPENSIONS FOR SPRAYING |
EP98950781A EP1033991B1 (en) | 1997-10-09 | 1998-10-06 | Mometasone furoate suspensions for nebulization |
CA002305256A CA2305256C (en) | 1997-10-09 | 1998-10-06 | Mometasone furoate suspensions for nebulization |
AU96743/98A AU9674398A (en) | 1997-10-09 | 1998-10-06 | Mometasone furoate suspensions for nebulization |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US94811897A | 1997-10-09 | 1997-10-09 | |
US08/948,118 | 1997-10-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1999018971A1 true WO1999018971A1 (en) | 1999-04-22 |
Family
ID=25487304
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1998/020480 WO1999018971A1 (en) | 1997-10-09 | 1998-10-06 | Mometasone furoate suspensions for nebulization |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP1033991B1 (en) |
JP (1) | JP3676674B2 (en) |
AT (1) | ATE216244T1 (en) |
AU (1) | AU9674398A (en) |
CA (1) | CA2305256C (en) |
DE (1) | DE69804998T2 (en) |
ES (1) | ES2172217T3 (en) |
WO (1) | WO1999018971A1 (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000051591A1 (en) * | 1999-03-03 | 2000-09-08 | Novartis Ag | Combinations of formoterol and mometasone furoate for asthma |
EP1530966A1 (en) * | 2003-10-22 | 2005-05-18 | MonteResearch S.r.l. | Process for the preparation of pharmaceutical suspensions for inhalation |
EP1683514A1 (en) | 2005-01-20 | 2006-07-26 | Eratech S.r.l. | Concentrated suspensions of drugs and their use to produce suspensions for inhalatory administration |
WO2007064912A2 (en) * | 2005-12-02 | 2007-06-07 | Elan Pharma International Limited | Mometasone compositions and methods of making and using the same |
US7811606B2 (en) | 2003-04-16 | 2010-10-12 | Dey, L.P. | Nasal pharmaceutical formulations and methods of using the same |
US7972626B2 (en) | 2003-04-16 | 2011-07-05 | Merck Patent Gmbh | Fluticasone propionate nasal pharmaceutical formulations and methods of using same |
US8129364B2 (en) | 2003-04-16 | 2012-03-06 | Dey Pharma, L.P. | Formulations and methods for treating rhinosinusitis |
US9907807B2 (en) | 2010-05-26 | 2018-03-06 | Almirall, S.A. | Topical pharmaceutical compositions |
US10945950B2 (en) | 2014-09-15 | 2021-03-16 | Verona Pharma Plc | Liquid inhalation formulation comprising RPL554 |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE9704186D0 (en) | 1997-11-14 | 1997-11-14 | Astra Ab | New composition of matter |
NZ550304A (en) * | 2001-10-26 | 2008-05-30 | Dey L P | An antimicrobial preservative-free albuterol inhalation solution for the relief of bronchospasm in children with asthma |
JP2010184937A (en) * | 2001-10-26 | 2010-08-26 | Dey Lp | Albuterol and ipratropium inhalation solution for relieving symptom of chronic obstructive pulmonary disease, kit, method for preparing one vessel containing the inhalation solution and method for preparing the inhalation solution |
EP1667687A1 (en) * | 2003-09-26 | 2006-06-14 | Schering Corporation | Pulmonary disease treatment |
WO2020070599A1 (en) * | 2018-10-05 | 2020-04-09 | Glenmark Specialty S.A. | Nebulization composition of mometasone |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992004365A1 (en) * | 1990-09-10 | 1992-03-19 | Schering Corporation | Mometasone furoate monohydrate, process for making same and pharmaceutical compositions |
EP0653205A1 (en) * | 1991-06-10 | 1995-05-17 | Schering Corporation | Non-chloroflurocarbon aerosol formulations |
WO1995020393A1 (en) * | 1994-01-27 | 1995-08-03 | Schering Corporation | Use of mometasone furoate for treating airway passage and lung diseases |
-
1998
- 1998-10-06 CA CA002305256A patent/CA2305256C/en not_active Expired - Fee Related
- 1998-10-06 ES ES98950781T patent/ES2172217T3/en not_active Expired - Lifetime
- 1998-10-06 AU AU96743/98A patent/AU9674398A/en not_active Abandoned
- 1998-10-06 JP JP2000515604A patent/JP3676674B2/en not_active Expired - Fee Related
- 1998-10-06 DE DE69804998T patent/DE69804998T2/en not_active Expired - Lifetime
- 1998-10-06 WO PCT/US1998/020480 patent/WO1999018971A1/en active IP Right Grant
- 1998-10-06 AT AT98950781T patent/ATE216244T1/en not_active IP Right Cessation
- 1998-10-06 EP EP98950781A patent/EP1033991B1/en not_active Expired - Lifetime
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992004365A1 (en) * | 1990-09-10 | 1992-03-19 | Schering Corporation | Mometasone furoate monohydrate, process for making same and pharmaceutical compositions |
EP0653205A1 (en) * | 1991-06-10 | 1995-05-17 | Schering Corporation | Non-chloroflurocarbon aerosol formulations |
WO1995020393A1 (en) * | 1994-01-27 | 1995-08-03 | Schering Corporation | Use of mometasone furoate for treating airway passage and lung diseases |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7566705B2 (en) | 1999-03-03 | 2009-07-28 | Novartis Ag | Combination of formoterol and mometasone furoate for asthma |
EP1325765A1 (en) * | 1999-03-03 | 2003-07-09 | Novartis AG | Combinations of Formoterol and Mometasone Furoate for Asthma |
WO2000051591A1 (en) * | 1999-03-03 | 2000-09-08 | Novartis Ag | Combinations of formoterol and mometasone furoate for asthma |
US7067502B2 (en) | 1999-03-03 | 2006-06-27 | Novartis Ag | Combinations of formoterol and mometasone furoate for asthma |
US8912174B2 (en) | 2003-04-16 | 2014-12-16 | Mylan Pharmaceuticals Inc. | Formulations and methods for treating rhinosinusitis |
US8309061B2 (en) * | 2003-04-16 | 2012-11-13 | Dey Pharma, L.P. | Formulations and methods for treating rhinosinusitis |
US9808471B2 (en) | 2003-04-16 | 2017-11-07 | Mylan Specialty Lp | Nasal pharmaceutical formulations and methods of using the same |
US9180126B2 (en) | 2003-04-16 | 2015-11-10 | Mylan Specialty L.P. | Formulations and methods for treating rhinosinusitis |
US7811606B2 (en) | 2003-04-16 | 2010-10-12 | Dey, L.P. | Nasal pharmaceutical formulations and methods of using the same |
US7972626B2 (en) | 2003-04-16 | 2011-07-05 | Merck Patent Gmbh | Fluticasone propionate nasal pharmaceutical formulations and methods of using same |
US7972627B2 (en) | 2003-04-16 | 2011-07-05 | Merck Patent Gmbh | Beclomethasone dipropionate monohydrate nasal pharmaceutical formulations and methods of using the same |
US8129364B2 (en) | 2003-04-16 | 2012-03-06 | Dey Pharma, L.P. | Formulations and methods for treating rhinosinusitis |
US8158154B2 (en) | 2003-04-16 | 2012-04-17 | Dey Pharma, L.P. | Nasal pharmaceutical formulations and methods of using the same |
US8663695B2 (en) | 2003-04-16 | 2014-03-04 | Mylan Specialty L.P. | Formulations and methods for treating rhinosinusitis |
EP1530966A1 (en) * | 2003-10-22 | 2005-05-18 | MonteResearch S.r.l. | Process for the preparation of pharmaceutical suspensions for inhalation |
US9155700B2 (en) | 2003-10-22 | 2015-10-13 | Chiesi Farmaceutici S.P.A. | Process for the preparation of pharmaceutical suspensions for inhalation |
EP1683514A1 (en) | 2005-01-20 | 2006-07-26 | Eratech S.r.l. | Concentrated suspensions of drugs and their use to produce suspensions for inhalatory administration |
WO2007064912A2 (en) * | 2005-12-02 | 2007-06-07 | Elan Pharma International Limited | Mometasone compositions and methods of making and using the same |
WO2007064912A3 (en) * | 2005-12-02 | 2007-10-25 | Elan Pharma Int Ltd | Mometasone compositions and methods of making and using the same |
US9907807B2 (en) | 2010-05-26 | 2018-03-06 | Almirall, S.A. | Topical pharmaceutical compositions |
US10945950B2 (en) | 2014-09-15 | 2021-03-16 | Verona Pharma Plc | Liquid inhalation formulation comprising RPL554 |
Also Published As
Publication number | Publication date |
---|---|
ES2172217T3 (en) | 2002-09-16 |
CA2305256C (en) | 2005-05-17 |
AU9674398A (en) | 1999-05-03 |
EP1033991B1 (en) | 2002-04-17 |
CA2305256A1 (en) | 1999-04-22 |
DE69804998T2 (en) | 2002-12-12 |
JP3676674B2 (en) | 2005-07-27 |
EP1033991A1 (en) | 2000-09-13 |
JP2001519397A (en) | 2001-10-23 |
DE69804998D1 (en) | 2002-05-23 |
ATE216244T1 (en) | 2002-05-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU710821B2 (en) | Fluticasone propionate formulations | |
US6187765B1 (en) | Mometasone furoate suspensions for nebulization | |
EP0536250B1 (en) | Aerosol drug formulations | |
EP1033991B1 (en) | Mometasone furoate suspensions for nebulization | |
US20090298802A1 (en) | Pharmaceutical Compositions | |
AU2010203026A1 (en) | Nasal pharmaceutical formulations and methods of using the same | |
PL207863B1 (en) | Process for preparation of a sterile suspension of corticosteroid particles for the administration by inhalation | |
EA012388B1 (en) | Aqueous suspensions of ciclesonide for nebulisation | |
EP1613281B1 (en) | Nasal pharmaceutical formulations and methods of using the same | |
DK2704724T3 (en) | Improved suspension formulation of beclomethasone dipropionate for administration by inhalation | |
EP1169065B1 (en) | Methacoline or histamine formulations for detecting asthma | |
MXPA00003476A (en) | Mometasone furoate suspensions for nebulization | |
WO1996013254A1 (en) | Pharmaceutical composition comprising atovaquone | |
CN101171023A (en) | Particle and preparation containing the particle | |
CN117224482A (en) | Inhalation preparation for treating IPF diseases and preparation method thereof | |
CN113133993A (en) | Suspension preparation for sterile inhalation and preparation method thereof | |
CN116407524A (en) | Monabivalve inhalation powder aerosol and preparation method thereof | |
CN113491677A (en) | Novel medicinal antiviral drug inhalant preparation and preparation method thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AU AZ BA BB BG BR BY CA CN CZ EE GD GE HR HU ID IL IS JP KG KR KZ LC LK LR LT LV MD MG MK MN MX NO NZ PL RO RU SG SI SK SL TJ TM TR TT UA US UZ VN YU |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 1998950781 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2305256 Country of ref document: CA Ref country code: CA Ref document number: 2305256 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2000/003476 Country of ref document: MX |
|
NENP | Non-entry into the national phase |
Ref country code: KR |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2000 515604 Kind code of ref document: A Format of ref document f/p: F |
|
WWP | Wipo information: published in national office |
Ref document number: 1998950781 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 1998950781 Country of ref document: EP |