WO2013005020A1 - Procédé de fabrication d'une composition de nébuliseur - Google Patents

Procédé de fabrication d'une composition de nébuliseur Download PDF

Info

Publication number
WO2013005020A1
WO2013005020A1 PCT/GB2012/051543 GB2012051543W WO2013005020A1 WO 2013005020 A1 WO2013005020 A1 WO 2013005020A1 GB 2012051543 W GB2012051543 W GB 2012051543W WO 2013005020 A1 WO2013005020 A1 WO 2013005020A1
Authority
WO
WIPO (PCT)
Prior art keywords
nebuliser
active agent
pharmaceutically active
solid dosage
composition
Prior art date
Application number
PCT/GB2012/051543
Other languages
English (en)
Inventor
Abdelbary ELHISSI
Fatmohn JAMA
Waqar AHMED
Kevin Taylor
Original Assignee
University Of Central Lancashire
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
Application filed by University Of Central Lancashire filed Critical University Of Central Lancashire
Publication of WO2013005020A1 publication Critical patent/WO2013005020A1/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
    • A61K9/0078—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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats

Definitions

  • the present invention relates to a method of producing a nebuliser composition, in particular a nebuliser composition for the nebulised pulmonary delivery of a pharmaceutically active agent.
  • the present invention also relates to a nebuliser composition obtained by this method, a method of nebulising a pharmaceutically active agent, a method of delivering a pharmaceutically active agent by nebulisation, a solid dosage form of a pharmaceutically active agent for use as a medicament in in situ nebulised pulmonary delivery, and a kit of parts.
  • drugs can be administered to patients via a variety of different delivery routes, including oral, parenteral, transdermal, pulmonary, intranasal, vaginal and rectal routes. Typically drugs are appropriately formulated for a pre-determined delivery route.
  • pulmonary drug delivery or delivery of drugs to the lungs can offer significant therapeutic advantages over other means of drug delivery.
  • pulmonary delivery is often preferred for drugs which act locally within the respiratory system, as faster onset of therapeutic effects can be achieved at lower doses with fewer systemic adverse effects.
  • pulmonary delivery can allow drugs to evade first pass hepatic effects. Such advantages are particularly marked where rapid delivery of a drug to the lungs is desirable, such as in the nebulised delivery of salbutamol to treat asthma and asthma attacks.
  • Nebulisers are unique in their ability to generate large volumes of aerosols from simply prepared solutions or dispersions (including suspensions) of the drug (O'Callaghan, C. and Barry, P.W., The science of nebulised drug delivery. Thorax, 52 (1997) Suppl 2, S31 -S44).
  • a typical example of a nebuliser is the air-jet nebuliser (also known as a compressor nebuliser), which operates by passing highly compressed gas through a small "venturi" nozzle, resulting in creation of liquid filaments that are then converted into aerosol droplets. Large droplets are recycled by the nebuliser baffles whilst smaller ones are released for inhalation (O'Callaghan and Barry, 1997).
  • the bronchodilator, salbutamol sulphate is typically supplied as an aqueous nebuliser composition for use in nebulised pulmonary delivery.
  • nebuliser compositions degrade over time via hydrolysis (Malkki, L, Tammilehto, S., Decomposition of salbutamol in aqueous solutions. I. The effect of pH, temperature and drug concentration. International Journal of Pharmaceutics, 63 (1990) 17-22). Therefore, current nebuliser compositions suffer from storage stability problems, especially in warmer climates where storage temperatures tend to be higher. As such, drug safety problems can arise from the prolonged storage of stocks of such nebuliser compositions.
  • a nebuliser composition comprising a pharmaceutically active agent dispersed and/or dissolved in a pharmaceutically acceptable diluent, said method comprising:
  • the inventors have found solid dosage forms of pharmaceutically active agents to be surprisingly effective for producing nebuliser compositions.
  • a solid dosage form to be a surprisingly useful nebulisable form of a pharmaceutically active agent.
  • Such solid dosage forms exhibit excellent storage stability as compared to currently available nebuliser compositions which are supplied in a pre-diluted form.
  • the solid dosage forms of the present invention are stable for prolongued periods under relatively warm storage conditions, and can be readily used to produce nebuliser compositions shortly before (or indeed simultaneously with) the nebulised pulmonary delivery thereof.
  • solid dosage forms are more volume efficient than their currently available pre-diluted counterparts, and thus easier and cheaper to transport and store.
  • a nebuliser composition obtainable by, obtained by, or directly obtained by the method of the first aspect.
  • a method of nebulising a pharmaceutically active agent comprising nebulising the nebuliser composition obtainable by, obtained by, or directly obtained by the method of the first aspect.
  • a method of delivering a pharmaceutically active agent by nebulisation comprising nebulising the nebuliser composition obtainable by, obtained by, or directly obtained by the method of the first aspect.
  • a solid dosage form of a pharmaceutically active agent in the manufacture of a medicament for treating a medical condition via in situ nebulised pulmonary delivery.
  • a solid dosage form of a pharmaceutically active agent for use as a medicament in in situ nebulised pulmonary delivery of the pharmaceutically active agent.
  • kits of parts comprising a solid dosage form of a pharmaceutically active agent, and a pharmaceutically acceptable diluent.
  • Figure 1 is a schematic view of a modern air-jet nebuliser showing the workings of the vent system during inhalation (left) and exhalation (right) [Source: O'Callaghan C, Barry PW, (1997). The science of nebulised drug delivery. Thorax, 52:Suppl 2, S31 -S44];
  • a “nebuliser composition” refers to a composition that is purpose made for the nebulised delivery of a pharmaceutically active agent.
  • solid dosage form refers to a solid form of a pharmaceutically active agent in admixture with one or more pharmaceutically acceptable excipients.
  • the terms "dispersed”, “dispersing” or “dispersion” are, unless otherwise stated, intended to refer to a dispersion of particles in a liquid medium. This includes, by way of example, a course dispersion of particles (i.e. suspended particles), a colloidal dispersion of particles, and even a nanodispersion.
  • the present invention provides a nebuliser composition obtainable by, obtained by, or directly obtained by the methods described herein.
  • the nebuliser composition is a liquid composition comprising:
  • the nebuliser composition is suitably an aqueous nebuliser composition.
  • the pharmaceutically active agent is dissolved in the pharmaceutically acceptable diluent.
  • the nebuliser composition may comprise a solubility enhancer, for instance where the active agent is not readily soluble in the diluent.
  • the nebuliser may be free of solubility enhancers, for instance, where the active agent is readily soluble in the diluent (such as where salbutamol sulphate is the active agent).
  • the pharmaceutically active agent is dispersed in the pharmaceutically acceptable diluent.
  • the nebuliser composition is a dispersion of the pharmaceutically active agent, suitably a colloidal dispersion thereof.
  • the nebuliser composition is a suspension of the pharmaceutically active agent (such as where a steroid is the active agent).
  • the nebuliser composition is a nanodispersion of the pharmaceutically active agent. Suitably such a nanodispersion comprises a nanocarrier.
  • the nebuliser composition is an isolated composition that is ready-for-use in the nebulised pulmonary delivery thereof.
  • the nebuliser composition is not isolated, but is rather generated in situ within a nebuliser.
  • the weight ratio of the solid dosage form to diluent is suitably between 1 :100 and 1 :10000, more suitably between 1 :1000 and 1 :5000, and most suitably between 1 :1500 and 1 :2500.
  • the active agent may be any pharmaceutically active agent suitable for pulmonary delivery via a nebuliser.
  • Pharmaceutically active agents that are prone to degradation such as salbutamol and salts thereof, are particularly suitable for use with the present invention.
  • Such degradable actives benefit, in terms of storage stability, from being stored in a solid dosage form before use in the nebulised pulmonary delivery of such actives.
  • references herein to any particular pharmaceutically active agent are also intended to refer to the pharmaceutically acceptable salts, solvates, and/or closely-related derivatives (e.g. pro-drugs) thereof.
  • the pharmaceutically active agent is an anti-asthma agent (e.g. salbutamol, beclometasone, budesonide, sodium cromoglicate, etc.).
  • Anti- asthma agents are particularly suitable for nebulised pulmonary delivery to patients, since they typically act locally within the respiratory system.
  • the anti-asthma agent is for emergency relief from asthma attacks.
  • the pharmaceutically active agent is salbutamol, or a salt thereof (e.g. salbutamol sulphate).
  • the pharmaceutically active agent is an antimicrobial agent for the treatment of pulmonary bacteria (e.g. tuberculosis) or fungi (e.g. aspergillosis).
  • the pharmaceutically active agent is an anti-cancer agent, especially for the treatment of pulmonary cancers or breast cancers.
  • the pharmaceutically active agent is a vaccine.
  • Many liquid vaccine formulations currently require refrigeration to remain stable, and so the use of solid dosage forms, which exhibit greater storage stability, in the nebulised pulmonary delivery of vaccines is particularly advantageous.
  • the pharmaceutically active agent comprises a hormone, DNA, or siRNA.
  • the pharmaceutically active agent is insulin (especially for the treatment of diabetes).
  • the pharmaceutically active agent is a protein or a gene (e.g. DNA or siRNA).
  • Current dosage forms of proteins and genes tend to suffer from instability problems, which creates storage issues.
  • Solid dosage forms of proteins or genes for use in nebulised pulmonary delivery thus provide a surprising solution to these problems.
  • solid dosage forms comprising GIT enzymes enable such macromolecules to be formulated as tablets for aerosol therapy via nebulisation in accordance with the present invention. Such treatments will considerably improve the quality of life of the relevant patients.
  • the diluent may be any diluent suitable for nebulisation.
  • the diluent is an aqueous diluent, such as water or a saline solution.
  • the diluent is a saline solution.
  • the saline solution comprises 0.1 to 3 wt% sodium chloride, more suitably 0.2 to 2.0 wt%, most suitably 0.5 to 1 .0 wt%.
  • Saline solutions are particularly suitable as diluents where the pharmaceutically active agent is an anti-asthma agent such as salbutamol.
  • the diluent may be selected to complement the pharmaceutically active agent.
  • the diluent contains a solubility enhancer (e.g. a pH adjuster, a surfactant, a co-solvent, a co-solute, a complexing agent) to assist solubility of the pharmaceutically active agent.
  • the diluent comprises an emulsifier (e.g. a surfactant) to facilitate emulsification of the pharmaceutically active agent in the diluent.
  • the diluent may be selected to complement the particular solid dosage form.
  • the diluent contains one or more additives to assist in the disintegration, dispersion, and/or dissolution of the solid dosage form.
  • One suitable additive may be a solubility enhancer, such as a suitable surfactant.
  • the present invention provides a use of a solid dosage form of a pharmaceutically active agent in the manufacture of a medicament for treating a medical condition via in situ nebulised pulmonary delivery of the pharmaceutically active agent.
  • the present invention provides a solid dosage form of a pharmaceutically active agent for use as a medicament in in situ nebulised pulmonary delivery of the pharmaceutically active agent.
  • a "solid dosage form” refers to a solid form of a pharmaceutically active agent in admixture with one or more pharmaceutically acceptable excipients. Any suitable solid dosage form of the pharmaceutically active agent may be used.
  • the solid dosage form may be a tablet, capsule, sachet, or granule formulation.
  • the solid dosage form is a compressed solid formulation.
  • the solid dosage form is suitably a conventional commercially available solid dosage form of the pharmaceutically active agent, such as a tablet, capsule, sachet, or granule formulation.
  • Such solid dosage forms comprise the pharmaceutically active agent in admixture with one or more pharmaceutically acceptable excipients.
  • the solid dosage form is a tablet.
  • the solid dosage form may be a dispersible formulation, such as a dispersible tablet, sachet or granule formulation, which is formulated to disperse and/or solubilise the drug in the diluent prior to administration.
  • the solid dosage form may be a conventional formulation that is normally taken orally in solid form (i.e. without prior dispersion in a diluent), such as a tablet or capsule. In such cases, dispersion and/or dissolution of the drug can be facilitated within the nebuliser by operation of the nebuliser.
  • the solid dosage form is dispersed and dissolved in situ within the nebuliser.
  • the solid dosage form may be dispersed and/or dissolved prior to being placed in the nebuliser and administered.
  • anti-asthma agents such as beclometasone dipropionate are lipophilic and thus solid dosage forms thereof advantageously contain a solubility enhancer to improve their compatibility with the methods of the present invention.
  • excipients e.g. lipids, surfactants
  • lipids, surfactants which protect their primary, secondary, and/or tertiary structure during nebulisation are particularly advantageous to mitigate against protein damage from shearing effects during nebulisation.
  • Solid dosage forms which lead to the formation of nanodispersions, in the methods of the present invention advantageously comprise a nanocarrier.
  • Particularly suitable solid dosage forms for use with the present invention are:
  • Oral solid dosage forms of any of the abovementioned pharmaceutically active agents especially compressed oral dosage forms.
  • the present invention provides a method of producing a nebuliser composition comprising a pharmaceutically active agent dispersed and/or dissolved in a pharmaceutically acceptable diluent, said method comprising:
  • the present invention provides a method of dispersing and/or dissolving a pharmaceutically active agent in a pharmaceutically acceptable diluent, said method comprising:
  • step b) is performed outside the nebuliser.
  • dispersion and/or dissolution of the pharmaceutically active agent in the diluent may be effected by manual or automated agitation, ultrasonication, or other techniques known in the art.
  • step b) takes place within a nebuliser.
  • step a) is performed outside the nebuliser such that an undispersed and/or undissolved mixture of the solid dosage form in the diluent (e.g. a heterogeneous slurry) is charged to a nebuliser reservoir (i.e. the reservoir arranged to receive standard pre-formed nebuliser compositions) before step b) is performed within the nebuliser.
  • step a) is performed within the nebuliser before step b) is then performed within the nebuliser (e.g.
  • step b) is facilitated by operation of the nebuliser.
  • the nebulisation conditions within an operating nebuliser facilitates step b).
  • Step b) may involve disintegration of the solid dosage form, for instance where the solid dosage form is a tablet.
  • the nebuliser is a compressed nebuliser (e.g. an air- jet nebuliser).
  • dispersion and/or dissolution of the pharmaceutically active agent in the diluent is suitably aided within the nebuliser by operating the nebuliser to produce aerosols under the influence of compressed gas passed through a small nozzle (e.g. "venturi" nozzle).
  • Step b) may also be aided by the recycling of aerosols (e.g. those which are too large for inhalation) within the nebuliser.
  • the nebuliser is a vibrating mesh nebuliser.
  • step b) may be aided within the nebuliser by operating the nebuliser to produce aerosols.
  • the nebuliser is an ultrasonic nebuliser.
  • step b) may be aided within the nebuliser by operating the nebuliser to expose the mixture of the solid dosage form in the diluent to ultrasonic radiation.
  • the nebuliser comprises a combination of features selected from the compressed nebuliser, the vibrating mesh nebuliser, and/or the ultrasonic nebuliser. In such cases, step b) may be aided within the nebuliser by operating some or all of this combination of features.
  • step b) is performed within the nebuliser by operating the nebuliser for a period of time before the nebulised pharmaceutically active agent is released for inhalation.
  • the period of time may suitably be at least 10 seconds, suitably at least 1 minute, suitably at least 5 minutes.
  • the period of time may suitably be less than 30 minutes, suitably less than 20 minutes, suitably less than 10 minutes.
  • Solid dosage forms were found to be surprisingly effective for in situ dispersion (and/or dissolution) and simultaneous nebulisation.
  • the nebulisation process itself was found to be a surprisingly efficient means of dispersing and/or dissolving such solid dosage forms, thereby allowing a nebuliser to serve a dual function of dispersing the solid dosage forms (which are much more stable on storage than standard nebuliser compositions) and nebulising the resulting dispersions to provide a nebulised form of the pharmaceutically active agent for pulmonary delivery to a patient.
  • the present invention provides a method of nebulising a pharmaceutically active agent, said method comprising nebulising the nebuliser composition obtainable by, obtained by, or directly obtained by the methods described herein.
  • the present invention also provides a method of delivering a pharmaceutically active agent by nebulisation, said method comprising nebulising the nebuliser composition obtainable by, obtained by, or directly obtained by the methods described herein.
  • a method suitably further comprises delivering the nebulised nebuliser composition to a patient via inhalation.
  • the method suitably further comprises delivering the nebulised nebuliser composition to the lungs of a patient suffering from asthma.
  • delivery of the nebuliser composition to the patient via inhalation takes place whilst the solid dosage form is still being dispersed and/or dissolved within the diluent in accordance with step b).
  • the method involves simultaneously:
  • the nebulised form of the nebuliser composition comprises aerosol particles having a droplet size less than 6 ⁇ .
  • the nebulised form of the nebuliser composition comprises aerosol particles having a droplet size more than 2 ⁇ .
  • the present invention provides a kit of parts comprising a solid dosage form of a pharmaceutically active agent, and a pharmaceutically acceptable diluent.
  • the kit further comprises instructions on carrying out any of the methods described herein.
  • Salbutamol sulphate (99%), sodium chloride, glacial acetic acid and sodium 1 - hexane sulphonate were purchased from Alfa Aesar, UK. Water and methanol used in high performance liquid chromatography (HPLC) were of HPLC grade and supplied by Fisher Scientific Ltd., UK. Salbutamol sulphate tablets (2.4 mg; equivalent to 2 mg salbutamol) (Actavis, UK) were supplied by a local pharmacy via a prescription for research purposes issued by the School of Pharmacy and Biomedical Sciences, University of Central Lancashire.
  • the nebuliser employed in the following examples was a Pari LC Sprint nebuliser linked to a Pari TurboBoy compressor (Pari GmbH, Germany).
  • FIG. 1 provides a schematic view of the air-jet nebuliser showing the workings of the vent system during inhalation (left) and exhalation (right).
  • the nebuliser 100 has:
  • nebuliser reservoir 40 for initially containing the nebuliser composition (or initially an undispersed and/or undissolved mixture of a solid dosage form and a diluent);
  • a first respiratory valve 60 which opens and closes respectively upon a patient's inspiration and expiration
  • a second respiratory valve 70 which closes and opens respectively on a patient's inspiration and expiration.
  • Modern air-jet nebulisers convert liquids into aerosols by employing compressed gas forced at high velocity through a narrow "venturi” nozzle 20. This creates an area of negative pressure above the liquid which, by the "Bernoulli effect", draws the liquid up a feed tube 30 as fine filaments that collapse into aerosol droplets because of liquid's surface tension (McCallion ONM, Taylor KMG, Bridges PA, Thomas M, Taylor AJ, (1996a). Jet nebulisers for pulmonary drug delivery. Int. J. Pharm., 130:1 -1 1 ; O'Callaghan C, Barry PW, (1997). The science of nebulised drug delivery. Thorax, 52:Suppl 2, S31 -S44).
  • Many modern jet nebulisers are designed to be breath-actuated or breath-enhanced. Pari jet nebulisers are common examples of breath-enhanced devices which operate by employing vent systems that close during exhalation (FIG. 1 ).
  • Example 1 Formulation mass output (standard nebuliser composition)
  • a drug solution was prepared by dissolving salbutamol sulphate (24 mg) (equivalent to 20 mg of salbutamol free-base) in NaCI (0.9%) solution (50 ml).
  • a Pari LC Sprint nebuliser was weighed and attached to a Pari TurboBoy compressor (Pari GmbH, Germany).
  • Salbutamol sulphate solution (5 ml) was placed in the nebuliser and the device was again weighed. Nebulisation commenced and completed to "dryness" (30 s after aerosol completely ceased) and the device weight was recorded and the aerosol output calculated.
  • Aerosol output (%) (mass delivered / liquid's mass before nebulisation) X 100%.
  • the nebuliser was rinsed with deionised water and the amount of the drug in the residual volume was determined using HPLC.
  • the drug output i.e. percentage of the weight nebulised
  • the drug output was determined by subtraction from the original amount of the drug before nebulisation (i.e. 2.4 mg).
  • the residual volume was rinsed and the rinsings passed through a 0.45 ⁇ GD/XP syringe filter to get rid of particulates left in the residual volume. Additional water was injected to collect the drug remaining within the filter. The collected salbutamol sulphate was analyzed using HPLC. Drug mass output was calculated by subtracting the amount in the residual volume from the original drug amount.
  • the mobile phase was prepared by mixing an aqueous solution of sodium 1 - hexane sulphonate hydrate (5mM) with methanol and glacial acetic acid (74:25:1 v/v/v).
  • HPLC analysis was performed using an Agilent 1200 instrument with a UV detector (Agilent, USA), salbutamol sulphate solution (10 ⁇ ) was injected via the autosampler G1329A in a C-18 Phenomenex column (4.6mmx250mm, 5 ⁇ ; Waters Phenomenex, UK) after setting up the temperature of the column at 40 °C and the flow rate of the mobile phase at 1 ml /min.
  • the amount of the drug was analyzed against a calibration curve at a UV wavelength of 276 nm.
  • the dose delivered in the "FPF” is also determined by the amount of the drug emitted from the nebuliser (i.e. drug output).
  • the overall dose released from the nebuliser was similar (P>0.05).
  • P>0.05 the overall dose released from the nebuliser was similar (P>0.05).
  • a novel and economical approach to delivering salbutamol sulphate aerosols was employed by dispersing a salbutamol sulphate tablet in an air-jet nebuliser. High drug output and "FPF" were produced and were comparable to those using a conventional salbutamol sulphate solution.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Dispersion Chemistry (AREA)
  • Otolaryngology (AREA)
  • Pulmonology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne un procédé de fabrication d'une composition de nébuliseur, en particulier d'une composition de nébuliseur appropriée pour une administration pulmonaire nébulisée à un patient. Le procédé consiste a) à introduire une forme posologique solide de l'agent pharmaceutiquement actif dans un diluant ; et b) à disperser et/ou à dissoudre l'agent pharmaceutiquement actif dans le diluant pour former la composition de nébuliseur. Des formes posologiques solides d'agents pharmaceutiquement actifs ont été trouvées comme étant de façon surprenante efficaces dans l'administration pulmonaire nébulisée de l'agent pharmaceutiquement actif, en particulier à l'endroit où la forme posologique solide est dispersée et/ou dissoute in situ à l'intérieur d'un nébuliseur et simultanément nébulisée pour administrer l'agent pharmaceutiquement actif au patient.
PCT/GB2012/051543 2011-07-01 2012-07-02 Procédé de fabrication d'une composition de nébuliseur WO2013005020A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB1111250.5 2011-07-01
GBGB1111250.5A GB201111250D0 (en) 2011-07-01 2011-07-01 Method of producing a nebuliser composition

Publications (1)

Publication Number Publication Date
WO2013005020A1 true WO2013005020A1 (fr) 2013-01-10

Family

ID=44511951

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2012/051543 WO2013005020A1 (fr) 2011-07-01 2012-07-02 Procédé de fabrication d'une composition de nébuliseur

Country Status (2)

Country Link
GB (1) GB201111250D0 (fr)
WO (1) WO2013005020A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11206872B2 (en) 2020-04-07 2021-12-28 Consumernext Labs Gmbh Stable-foam dispensing device and cartridge

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999017754A1 (fr) * 1997-10-08 1999-04-15 Sepracor Inc. Forme posologique pour administration d'aerosol
DE19847968A1 (de) * 1998-10-17 2000-04-20 Boehringer Ingelheim Pharma Verschlußkappe und Behälter als Zweikammer-Kartusche für Vernebler zur Erzeugung von Aerosolen
US20010009151A1 (en) * 1996-04-19 2001-07-26 Dieter Hochrainer Two-chamber cartridge for propellant-free metering aerosols
EP1172099A1 (fr) * 2000-06-26 2002-01-16 Purzer Pharmaceutical Co., Ltd. Procédé de transfert d'un ou plusieurs agents actifs entre phases différentes

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20010009151A1 (en) * 1996-04-19 2001-07-26 Dieter Hochrainer Two-chamber cartridge for propellant-free metering aerosols
WO1999017754A1 (fr) * 1997-10-08 1999-04-15 Sepracor Inc. Forme posologique pour administration d'aerosol
DE19847968A1 (de) * 1998-10-17 2000-04-20 Boehringer Ingelheim Pharma Verschlußkappe und Behälter als Zweikammer-Kartusche für Vernebler zur Erzeugung von Aerosolen
EP1172099A1 (fr) * 2000-06-26 2002-01-16 Purzer Pharmaceutical Co., Ltd. Procédé de transfert d'un ou plusieurs agents actifs entre phases différentes

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
HEYDER, J.: "Effect of cystic fibrosis on inhaled aerosol boluses.", AM. REV. RESPIR. DIS., vol. 140, 1989, pages 1317 - 1324
MAIKKI, L.; TAMMILEHTO, S.: "Decomposition of salbutamol in aqueous solutions. . The effect of pH, temperature and drug concentration.", INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 63, 1990, pages 17 - 22
MCCALLION ONM; TAYLOR KMG; BRIDGES PA; THOMAS M; TAYLOR AJ: "Jet nebulisers for pulmonary drug delivery", INT. J. PHARM., vol. 130, 1996, pages 1 - 11
O'CALLAGHAN C; BARRY PW: "The science of nebulised drug delivery.", THORAX, vol. 52, no. 2, 1997, pages S31 - S44
O'CALLAGHAN, C.; BARRY, P.W.: "The science of nebulised drug delivery.", THORAX, vol. 52, no. 2, 1997, pages S31 - S44
STAHLHOFEN, W.; GEBHART, J; HEYDER, J.: "Experimental determination of the regional deposition of aerosol particles in the human respiratory tract.", AM. IND. HYG. ASSOC. J., vol. 41, 1980, pages 385 - 398

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11206872B2 (en) 2020-04-07 2021-12-28 Consumernext Labs Gmbh Stable-foam dispensing device and cartridge

Also Published As

Publication number Publication date
GB201111250D0 (en) 2011-08-17

Similar Documents

Publication Publication Date Title
KR20100091970A (ko) 파킨슨병 치료용 조성물
JP2017509684A5 (fr)
JP2012082229A (ja) 抗コリン作用薬、コルチコステロイドおよび長時間作用性βアゴニストを合わせる薬物および方法
JP2017528479A (ja) Ｒｐｌ５５４を含む液体吸入製剤
CN107998109A (zh) 药物组合物
JP2014516062A (ja) ウメクリジニウム及びコルチコステロイドを含む組合せ
TW200524615A (en) Aqueous suspensions of ciclesonide for nebulisation
JP5501451B2 (ja) 咳の治療のためのテオブロミン
CN105209013A (zh) 喷雾干燥制剂经喷雾混合的脱非晶化
CN105307639B (zh) 包含与载体颗粒结合的活性剂纳米颗粒的干药物组合物
RU2582218C2 (ru) Способ получения дозирующего распыляющего ингалятора для лечения респираторного заболевания
RU2611665C2 (ru) Улучшенный состав суспензии кортикостероида для ингаляционного введения
CN107106516A (zh) 药物组合产品
WO2013005020A1 (fr) Procédé de fabrication d'une composition de nébuliseur
TW200922600A (en) DHEAS inhalation compositions
EP3485888A1 (fr) Composition médicamenteuse pour inhalation
JP2023543352A (ja) 噴霧器および噴霧化された抗ウイルス薬
TWI332403B (fr)
WO2015065219A1 (fr) Solution de bromure d'ipratropium
US20100291221A1 (en) Method of administering dose-sparing amounts of formoterol fumarate-budesonide combination particles by inhalation
JP6908523B2 (ja) ネブライザー用組成物
KR20220080127A (ko) 폐 질환을 위한 흡입 가능한 건조 분말 조성물
Kantar What Makes Flunisolide Different Among Inhaled Corticosteroids Used for Nebulization
WO2023003593A1 (fr) Formulations de biguanide pulmonaire
EP2429297A1 (fr) Procédé d'administration de quantités posologiques minimales de particules d'une association de fumarate de formotérol-budésonide par inhalation

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12733208

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 12733208

Country of ref document: EP

Kind code of ref document: A1