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WO1998001147A1 - Formulation d'une solution d'aerosol medicinal de cyclosporine a - Google Patents

Formulation d'une solution d'aerosol medicinal de cyclosporine a Download PDF

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Publication number
WO1998001147A1
WO1998001147A1 PCT/GB1997/001851 GB9701851W WO9801147A1 WO 1998001147 A1 WO1998001147 A1 WO 1998001147A1 GB 9701851 W GB9701851 W GB 9701851W WO 9801147 A1 WO9801147 A1 WO 9801147A1
Authority
WO
WIPO (PCT)
Prior art keywords
formulation according
solution formulation
pharmaceutical aerosol
aerosol solution
cyclosporin
Prior art date
Application number
PCT/GB1997/001851
Other languages
English (en)
Inventor
Alexander Bell
Original Assignee
Rhone-Poulenc Rorer Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB9614326.8A external-priority patent/GB9614326D0/en
Application filed by Rhone-Poulenc Rorer Limited filed Critical Rhone-Poulenc Rorer Limited
Priority to AU34538/97A priority Critical patent/AU3453897A/en
Priority to JP10504948A priority patent/JP2000514085A/ja
Priority to EP97930662A priority patent/EP0914143A1/fr
Publication of WO1998001147A1 publication Critical patent/WO1998001147A1/fr

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
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A61K38/13—Cyclosporins
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A61K9/124—Aerosols; Foams characterised by the propellant

Definitions

  • This invention relates to the administration of Cyclosporin A by inhalation via a solution aerosol formulation.
  • Such administrations will have particular benefits in the treatment of asthma or other respiratory diseases but are also expected to provide a convenient method of administering the drug for other purposes such as immunosuppression, treatment of auto-immune diseases, antiparasitic treatments, etc.
  • Cyclosporin A was developed as an immunosuppressant but has more recently been proposed as a treatment for asthma and other respiratory diseases.
  • EP-Al- 0504761 deals with the use of Cyclosporin A in pulmonary delivery systems for this purpose, and is primarily concerned with the administration via inhalation of a particular crystalline form of Cyclosporin A designated CY-A X-III.
  • Cyclosporin A as a solution in chlorofluorocarbon propellants in aerosol inhalation systems is also described. This is not a preferred option however, it being stated that the administration of Cyclosporin A in solution will have none of the advantages of administration of CY-A X-III.
  • WO 95/24892 describes the use of tocopherol and derivatives as surfactants to stabilise suspensions of a number of medicaments in hydrofluorocarbon propellants such as HFC 134a (1,1,1,2- tetrafluoroethane) and HFC 227 (1,1,1,2,3,3,3- heptafluoropropane) .
  • HFC 134a 1,1,1,2- tetrafluoroethane
  • HFC 227 1,1,1,2,3,3,3- heptafluoropropane
  • WO 96/06598 describes the use of polyglycolised glycerides in similar formulations and also exemplifies suspensions of Cyclosporin A in HFC 134a.
  • Cyclosporin A is sufficiently insoluble in the related hydrofluorocarbon, HFC 134a, to be used in a suspension rather than a solution formulation.
  • Cyclosporin A in HFC 227 is such that no co-solvent is required, although excipients may be added for other principal purposes, such as to improve valve function.
  • Excipients conventionally used in pharmaceutical aerosol formulations may be added if required, in particular excipients to improve valve lubrication and/or excipients to modify flavour.
  • Particular lubricants that may be mentioned include ethanol and polyethoxylated compounds, especially polyethylene glycol . Either 96% or absolute ethanol may conveniently be used.
  • polyethylene glycol with a mean molecular weight between 200 to 3000, preferably between 400 to 2000, e.g. 1500, is preferred.
  • Examples of other polyethoxylated compounds that may be used as lubricants include polysorbates, e.g. Polysorbate 80, and alkyl aryl polyether alcohols, e.g. tyloxapol .
  • Examples of other lubricating excipients that may be mentioned include high molecular weight fully halogenated chlorofluorocarbons and esters of medium chain fatty acids, lecithins, oleic acid or ⁇ orbitan esters.
  • the concentration of lubricant will depend on the type of lubricant and the nature of the valve. Ethanol addition will normally be less than 10%v/v, preferably between 2% to 7% v/v (eg about 5%v/v) .
  • the concentration of other lubricants will typically fall within the range of about 0.01 to 4%v/v, more typically about 0.1 to 2%v/v. If necessary a small amount of polar liquid, including ethanol, may be added as adjuvant to help dissolve such lubricants.
  • Flavour modifying excipients include peppermint oil, menthol, Dentomint (Dentomint is a trade name) , saccharin, saccharin sodium and aspartame. A solid excipient, preferably milled to a low particle size to reduce settling, may be used.
  • the concentration of flavouring excipient will typically be 0.005 to 4%v/v, more typically 0.01 to l%v/v.
  • the concentration of Cyclosporin A in the solution will be in the range 1 to 400mg/ml, more preferably in the range 5 to lOOmg/ml and most preferably in the range of about 10 to 50mg/ml.
  • Cyclosporin A may preferably constitute up to about 5% weight per total volume of solution.
  • HFC 227 will generally be used as sole propellant
  • formulations also comprising one or more different propellants are also included within the scope of the invention, provided that there is sufficient HFC 227 present to maintain a stable solution at the concentration required to deliver an effective dose of the medicament.
  • the alternative propellant or propellants will not be chlorocarbons or chlorofluorocarbons .
  • propellants which may be used include HFC 134a, HFC 152, low molecular weight hydrocarbons and dimethyl ether.
  • Formulations containing one or more additional medicaments are also considered to be within the scope of the invention.
  • the additional medicaments may also be in solution or they may be in the form of a suspension of fine drug particles in the conventional manner. In this latter case surfactants or adjuvants commonly used to stabilise such suspensions may be present.
  • Formulations according to the invention may be used to manufacture pharmaceutical aerosols for treatment of respiratory diseases, in particular respiratory obstructive airways diseases (ROAD) such as asthma.
  • ROAD respiratory obstructive airways diseases
  • Cyclosporin A for the manufacture of a solution aerosol formulation in 1, 1, 1, 2 , 3 , 3 , 3-heptafluoropropane for the treatment of respiratory diseases, in particular respiratory obstructive airways diseases such as asthma.
  • a further aspect of the invention provides a method of treating respiratory diseases, including ROAD, comprising administering by inhalation a spray or aerosol derived from a formulation comprising Cyclosporin A dissolved in 1,1,1,2,3,3,3- heptafluoropropane .
  • a pharmaceutical aerosol device containing a formulation comprising Cyclosporin A dissolved in 1, 1, 1, 2 , 3 , 3, 3 -heptafluoropropane.
  • the formulation according to the invention will be used in a standard metered dose aerosol inhaler device (MDI) .
  • MDI metered dose aerosol inhaler device
  • Such devices typically use a 50 ⁇ l or lOO ⁇ l valve.
  • a typical dose of Cyclosporin A for inhalation is expected to be approximately 25mg per day, delivered in individual doses of 1 to lOmg per inhalation, preferably 1 to 5mg per inhalation. This will require a solution concentration of Cyclosporin A of about 10 to lOOmg/ml. It will be appreciated that different doses may be required depending on the disease to be treated, and solution concentration and/or valve size can be varied accordingly.
  • MDI devices commonly use a spacer to increase the path length between spray orifice and the mouth of the patient. This slows down the aerosol jet and allows larger aerosol particles to settle out before entering the patient's mouth. Whilst not essential to the operation of the present invention the use of a spacer has been found to reduce the incidence of larger particles with minimum effect on respirable fraction.
  • the formulations according to the invention may be filled into canisters suitable for delivering pharmaceutical aerosol formulations.
  • Canisters generally comprise a container capable of withstanding the vapour pressure of the propellant used such as a plastic or plastic-coated glass bottle or preferably a metal can, for example an aluminium can which may optionally be anodised, lacquer-coated and/or plastic-coated, and closed with a metering valve.
  • the metering valves are designed to deliver a metered amount of the formulation per actuation and incorporate a gasket to prevent leakage of propellant through the valve.
  • the gasket may comprise any suitable elastomeric material such as for example low density polyethylene, chlorobutyl, black and white butadiene-acrylonitrile rubbers, butyl rubber and neoprene .
  • suitable valves are commercially available from manufacturers well known in the aerosol industry, for example, from Valois, France, Bespak pic. UK and 3M-Neotechnic Ltd, UK.
  • Each filled canister is conveniently fitted into a suitable channelling device prior to use to form a metered dose inhaler for administration to the medicament into the lungs or nasal cavity of a patient.
  • Suitable channelling devices comprise for example a valve actuator and a cylindrical or cone- like passage through which medicament may be delivered from the filled canister via the metering valve to the nose or mouth of a patient, e.g. a mouthpiece actuator.
  • each filled canister for use in a metered dose inhaler contains 100 to 250 metered doses or puffs of medicament.
  • Administration of medicament may be indicated for the treatment of mild, moderate or severe acute or chronic symptoms or for prophylactic treatment. It will be appreciated that the precise dose administered will depend on the age and condition of the patient and the frequency of administration and will ultimately be at the discretion of the attendant physician. Typically, administration may be one or more times, for example from 1 to 8 times per day, giving for example 1, 2, 3 or 4 puffs each time.
  • the filled canisters and metered dose inhalers described herein comprise further aspects of the present invention.
  • Cyclosporin A was weighed into a plastic-coated glass bottle and a continuous flow valve crimped onto the bottle. Propellant was added to the bottle from an aerosol can using a suitable transfer valve. The quantity added was chosen to leave some undissolved Cyclosporin A and therefore ensure a saturated solution. The suspension was left to equilibrate overnight at 20°C and filtered through a 0.5 ⁇ m polytetrafluoroethylene (PTFE) membrane using a pressure filtration apparatus into an empty crimped receptor bottle to give a clear saturated solution. The weight of solution in the bottle was determined and the propellant was then carefully vented off to leave the Cyclosporin A. This was dissolved in a measured volume of ethanol and the concentration of the solution measured using High Pressure Liquid Chro atography (HPLC) in order to give the quantity of Cyclosporin A in the original propellant solution.
  • HPLC High Pressure Liquid Chro atography
  • EXAMPLE 2 500mg of Cyclosporin A was weighed into a plastic-coated glass bottle. 10ml of HFC 227 was added and a lOO ⁇ l metering valve immediately crimped into place. The resulting aerosol delivered 5mg Cyclosporin A per actuation. The solution was stable over a period of three months.
  • EXAMPLE 3 A number of formulations containing ethanol were prepared. The ethanol wa ⁇ added to act as lubricant for the aerosol valve and improve dose reproducibility. An ethanolic solution of Cyclosporin A was produced at a concentration suitable for producing the required final concentration in the aerosol. A measured quantity was added to a standard aluminium aerosol can and a metering valve crimped on top. The required amount of propellant was added to the can through the valve. All solutions were found to be stable to chemical degradation on storage at 45°C for one month and to precipitation at temperatures as low as -78°C.
  • HFC 227 formulations were subjected to the standard Anderson Impactor test for respirable fraction with the following results:
  • Cyclosporin A (mg/ml) 50 50 25 25 10

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dispersion Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Otolaryngology (AREA)
  • Pulmonology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention porte sur la formulation d'une solution de Cyclosporine A dans un 1,1,1,2,3,3,3-heptafluoropropane, cette formulation pouvant être administrée à un patient par inhalation à l'aide de n'importe quel aérosol médicinal de type classique. A cette formulation, on peut également ajouter des excipients de type classique normalement utilisés dans les formulations d'aérosol médicinal pour aider à la lubrication des valves ou pour améliorer le goût. Outre la Cyclosporine A, on peut ajouter d'autres médicaments à la solution ou à la suspension. On peut également ajouter d'autres propulseurs au 1,1,1,2,3,3,3-heptafluoropropane.
PCT/GB1997/001851 1996-07-08 1997-07-07 Formulation d'une solution d'aerosol medicinal de cyclosporine a WO1998001147A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU34538/97A AU3453897A (en) 1996-07-08 1997-07-07 Medicinal cyclosporin-a aerosol solution formulation
JP10504948A JP2000514085A (ja) 1996-07-08 1997-07-07 医薬シクロスポリンａエーロゾル溶液処方物
EP97930662A EP0914143A1 (fr) 1996-07-08 1997-07-07 Formulation d'une solution d'aerosol medicinal de cyclosporine a

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB9614326.8A GB9614326D0 (en) 1996-07-08 1996-07-08 Medicament
GB9614326.8 1996-07-08
US2304896P 1996-08-02 1996-08-02
US60/023,048 1996-08-02

Publications (1)

Publication Number Publication Date
WO1998001147A1 true WO1998001147A1 (fr) 1998-01-15

Family

ID=26309665

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1997/001851 WO1998001147A1 (fr) 1996-07-08 1997-07-07 Formulation d'une solution d'aerosol medicinal de cyclosporine a

Country Status (4)

Country Link
EP (1) EP0914143A1 (fr)
JP (1) JP2000514085A (fr)
AU (1) AU3453897A (fr)
WO (1) WO1998001147A1 (fr)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2326334A (en) * 1997-06-13 1998-12-23 Chiesi Farma Spa Pharmaceutical aerosol compositions
WO1999065464A1 (fr) * 1998-06-18 1999-12-23 Boehringer Ingelheim Pharmaceuticals, Inc. Preparations pharmaceutiques pour aerosols a deux principes actifs ou plus
WO2000030607A1 (fr) * 1998-11-25 2000-06-02 Chiesi Farmaceutici S.P.A. Composition pharmaceutique en aerosol contenant hfa 227 et hfa 137
WO2000045834A3 (fr) * 1999-02-05 2000-12-21 Univ Pittsburgh Utilisation de cyclosporine en aerosol pour la prevention et le traitement de maladies pulmonaires
US6423298B2 (en) 1998-06-18 2002-07-23 Boehringer Ingelheim Pharmaceuticals, Inc. Pharmaceutical formulations for aerosols with two or more active substances
GB2332372B (en) * 1997-12-08 2002-08-14 Minnesota Mining & Mfg Pharmaceutical aerosol compositions
WO2004069223A3 (fr) * 2003-02-06 2005-03-17 Cipla Ltd Compositions pharmaceutiques et leurs utilisations
US6964759B2 (en) 2000-02-22 2005-11-15 Chiesi Farmaceutici S.P.A. Formulations containing an anticholinergic drug for the treatment of chronic obstructive pulmonary disease
US6967017B1 (en) 1999-07-23 2005-11-22 Chiesi Farmaceutici S.P.A. Formulations of steroid solutions for inhalatory administration
US7018618B2 (en) 2000-05-22 2006-03-28 Chiesi Farmaceutici S.P.A. Stable pharmaceutical solution formulations for pressurized metered dose inhalers
US7223381B2 (en) 1998-11-25 2007-05-29 Chiesi Farmaceutici S.P.A. Pressurised metered dose inhalers (MDI)
WO2007109530A1 (fr) * 2006-03-20 2007-09-27 Allergan, Inc. Compositions de cyclosporine a
US7381402B2 (en) 2004-02-27 2008-06-03 Chiesi Farmaceutici S.P.A. Stable pharmaceutical solution formulations for pressurized metered dose inhalers
US7601336B2 (en) 1997-06-13 2009-10-13 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
US7696178B2 (en) 2001-07-02 2010-04-13 Chiesi Farmaceutici S.P.A. Optimised formulation of tobramycin for aerosolization
US9161963B2 (en) 2005-12-06 2015-10-20 Pari Pharma Gmbh Pharmaceutical compositions comprising cyclosporin

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7851419B2 (en) * 2005-09-12 2010-12-14 Nawaz Ahmad Substantially anhydrous sprayable personal lubricant

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0504760A1 (fr) * 1991-03-18 1992-09-23 Sandoz Ltd. Formulation de cyclosporine pour administration par voie pulmonaire
EP0633019A1 (fr) * 1993-07-08 1995-01-11 ASTA Medica Aktiengesellschaft Conditionnement de gaz comprimé avec polyoxyéthylène glyceryl esters d'acide gras comme stabilisateurs de suspensions et lubricants pour valves
WO1995024892A1 (fr) * 1994-03-14 1995-09-21 Abbott Laboratories Formule d'un aerosol medicamenteux contenant de la vitamine e
WO1996006598A1 (fr) * 1994-08-26 1996-03-07 Abbott Laboratories Formulations medicamenteuses en aerosol contenant des glycerides polyglycolyses
WO1996011943A1 (fr) * 1994-10-14 1996-04-25 Astra Aktiebolag Nouveaux peptides a effets immunodulateurs

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0504760A1 (fr) * 1991-03-18 1992-09-23 Sandoz Ltd. Formulation de cyclosporine pour administration par voie pulmonaire
EP0633019A1 (fr) * 1993-07-08 1995-01-11 ASTA Medica Aktiengesellschaft Conditionnement de gaz comprimé avec polyoxyéthylène glyceryl esters d'acide gras comme stabilisateurs de suspensions et lubricants pour valves
WO1995024892A1 (fr) * 1994-03-14 1995-09-21 Abbott Laboratories Formule d'un aerosol medicamenteux contenant de la vitamine e
WO1996006598A1 (fr) * 1994-08-26 1996-03-07 Abbott Laboratories Formulations medicamenteuses en aerosol contenant des glycerides polyglycolyses
WO1996011943A1 (fr) * 1994-10-14 1996-04-25 Astra Aktiebolag Nouveaux peptides a effets immunodulateurs

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8420058B2 (en) 1997-06-13 2013-04-16 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
US7601336B2 (en) 1997-06-13 2009-10-13 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
GB2326334A (en) * 1997-06-13 1998-12-23 Chiesi Farma Spa Pharmaceutical aerosol compositions
GB2332372B (en) * 1997-12-08 2002-08-14 Minnesota Mining & Mfg Pharmaceutical aerosol compositions
EP1037604B1 (fr) * 1997-12-08 2005-01-26 Minnesota Mining And Manufacturing Company Compositions pharmaceutiques d'aerosols
AU759222B2 (en) * 1998-06-18 2003-04-10 Boehringer Ingelheim Pharmaceuticals, Inc. Pharmaceutical formulations for aerosols with two or more active substances
KR100600423B1 (ko) * 1998-06-18 2006-07-13 베링거 인겔하임 파마슈티칼즈, 인코포레이티드 2개 이상의 활성 물질을 포함하는 연무질 약제학적 제형
US6423298B2 (en) 1998-06-18 2002-07-23 Boehringer Ingelheim Pharmaceuticals, Inc. Pharmaceutical formulations for aerosols with two or more active substances
BG65252B1 (bg) * 1998-06-18 2007-10-31 Boehringer Ingelheim Pharmaceuticals, Inc. Фармацевтични състави за аерозоли с две или повече активни вещества
HRP20000867B1 (en) * 1998-06-18 2010-10-31 Boehringer Ingelheim Pharmaceuticals Inc. Pharmaceutical formulations for aerosols with two or more active substances
WO1999065464A1 (fr) * 1998-06-18 1999-12-23 Boehringer Ingelheim Pharmaceuticals, Inc. Preparations pharmaceutiques pour aerosols a deux principes actifs ou plus
CZ300910B6 (cs) * 1998-06-18 2009-09-09 Boehringer Ingelheim Pharmaceuticals, Inc. Farmaceutický prostredek
US7223381B2 (en) 1998-11-25 2007-05-29 Chiesi Farmaceutici S.P.A. Pressurised metered dose inhalers (MDI)
US8142763B2 (en) 1998-11-25 2012-03-27 Chiesi Farmaceutici S.P.A. Pressurized metered dose inhalers (MDI) containing a solution comprising ipratropium bromide, HFA propellant, and co-solvent and comprising a container with a specific internal surface composition and/or lining
JP2002530316A (ja) 1998-11-25 2002-09-17 キエシ・フアルマチエウテイチ・ソチエタ・ペル・アチオニ Ｈｆａ２２７およびｈｆａ１３７を含有する製薬学的エアゾル組成物
US6713047B1 (en) 1998-11-25 2004-03-30 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition containing HFA 227 and HFA 134a
US7347199B1 (en) 1998-11-25 2008-03-25 Chiesi Farmaceutici S.P.A. Pressurised metered dose inhalers (MDI)
WO2000030607A1 (fr) * 1998-11-25 2000-06-02 Chiesi Farmaceutici S.P.A. Composition pharmaceutique en aerosol contenant hfa 227 et hfa 137
US8158110B2 (en) 1999-02-05 2012-04-17 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Use of aerosolized cyclosporine for prevention and treatment of pulmonary disease
WO2000045834A3 (fr) * 1999-02-05 2000-12-21 Univ Pittsburgh Utilisation de cyclosporine en aerosol pour la prevention et le traitement de maladies pulmonaires
US6967017B1 (en) 1999-07-23 2005-11-22 Chiesi Farmaceutici S.P.A. Formulations of steroid solutions for inhalatory administration
US6964759B2 (en) 2000-02-22 2005-11-15 Chiesi Farmaceutici S.P.A. Formulations containing an anticholinergic drug for the treatment of chronic obstructive pulmonary disease
US7018618B2 (en) 2000-05-22 2006-03-28 Chiesi Farmaceutici S.P.A. Stable pharmaceutical solution formulations for pressurized metered dose inhalers
US7696178B2 (en) 2001-07-02 2010-04-13 Chiesi Farmaceutici S.P.A. Optimised formulation of tobramycin for aerosolization
US7939502B2 (en) 2001-07-02 2011-05-10 Chiesi Farmaceutici S.P.A. Optimised formulation of tobramycin for aerosolization
US8168598B2 (en) 2001-07-02 2012-05-01 Chiesi Farmaceutici S.P.A. Optimised formulation of tobramycin for aerosolization
WO2004069223A3 (fr) * 2003-02-06 2005-03-17 Cipla Ltd Compositions pharmaceutiques et leurs utilisations
US7381402B2 (en) 2004-02-27 2008-06-03 Chiesi Farmaceutici S.P.A. Stable pharmaceutical solution formulations for pressurized metered dose inhalers
US9161963B2 (en) 2005-12-06 2015-10-20 Pari Pharma Gmbh Pharmaceutical compositions comprising cyclosporin
US9724382B2 (en) 2005-12-06 2017-08-08 Pari Pharma Gmbh Pharmaceutical compositions comprising cyclosporin
WO2007109530A1 (fr) * 2006-03-20 2007-09-27 Allergan, Inc. Compositions de cyclosporine a

Also Published As

Publication number Publication date
EP0914143A1 (fr) 1999-05-12
AU3453897A (en) 1998-02-02
JP2000514085A (ja) 2000-10-24

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