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EP2278959A2 - Support composite pour médicaments pulvérulents, procédé de fabrication du support et équipement pour la fabrication des particules de support composite - Google Patents

Support composite pour médicaments pulvérulents, procédé de fabrication du support et équipement pour la fabrication des particules de support composite

Info

Publication number
EP2278959A2
EP2278959A2 EP09735696A EP09735696A EP2278959A2 EP 2278959 A2 EP2278959 A2 EP 2278959A2 EP 09735696 A EP09735696 A EP 09735696A EP 09735696 A EP09735696 A EP 09735696A EP 2278959 A2 EP2278959 A2 EP 2278959A2
Authority
EP
European Patent Office
Prior art keywords
carrier
particles
composite
solution
particle
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
EP09735696A
Other languages
German (de)
English (en)
Inventor
Leon Gradon
Tomasz Sosnowski
Michal Pirozynski
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Przedsiebiorstwo Produkcji Farmaceutycznej Hasco-L
Original Assignee
PRZEDSIEBIORSTWO PRODUKCJI FARMACEUTYCZNEJ HASCO-LEK SA
HAN STANISTAW
Przed Produkcji Farmaceutycznej Hasco Lek S A
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 PRZEDSIEBIORSTWO PRODUKCJI FARMACEUTYCZNEJ HASCO-LEK SA, HAN STANISTAW, Przed Produkcji Farmaceutycznej Hasco Lek S A filed Critical PRZEDSIEBIORSTWO PRODUKCJI FARMACEUTYCZNEJ HASCO-LEK SA
Priority to EP11150820A priority Critical patent/EP2340816A1/fr
Priority to EP11150815A priority patent/EP2340817A1/fr
Publication of EP2278959A2 publication Critical patent/EP2278959A2/fr
Ceased legal-status Critical Current

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
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Definitions

  • the object of the present invention is a composite carrier for powdery drugs, a method of the drug carrier manufacturing, and a plant for manufacturing the composite carrier particles in a form of a solid particle being a composite of surfactants and mucolytics (mucolytic substances), which is a carrier of a drug delivered into the organism by inhalation.
  • Aerosol therapy is one of the most expansively developing techniques of drug administration.
  • the respiratory system which is the broadest way of contact between the organism and external environment, provides the opportunity for effective delivery of the drug in a system therapy.
  • a biologically active ingredient deposited in the area of alveoli, can be released to the circulatory system in a controlled way.
  • Modern technical solutions offer drug particles containing biologically active ingredients acting as analgesics or antibiotics. Insulin may be administered by inhalation as well.
  • the aerosol therapy is a basic method of treatment of the respiratory system, including such diseases of civilization like asthma. It is also the main method of treatment for the chronic obstructive pulmonary disease (COPD).
  • COPD chronic obstructive pulmonary disease
  • the drug is conversed into the aerosol form, i.e. a stable dispersion of droplets of liquid or solid particles in the inhaled air.
  • the drug in liquid form is conversed into the aerosol by atomization with ultrasonic waves, or by dispersing in nozzle with compressed air.
  • the drag in solid form is pulverized and conversed into aerosol from a suspension in a volatile medium, which was at first produced under increased pressure, and then expanded in the nozzle.
  • the volatile agent evaporates, and particles form aerosol which is inhaled by a patient.
  • the particles of active ingredient are deposited on a surface of bigger particles that are pharmacologically neutral.
  • particles of the active ingredient detach from the carrier.
  • the carrier particles having large diameters, are captured in head airways, while the smaller drug particles enter the further parts of the respiratory system.
  • the drug particles Having been deposited in the bronchial tree, the drug particles penetrate through a layer of mucus that covers bronchi, and enter the receptors located in cytoplasm of epithelium cells. Effectiveness of penetration through mucus is diminished due to its stickiness.
  • the therapeutic power is badly reduced in case of respiratory tract illnesses connected additionally with mucus overproduction (e.g. mucoviscidosis or chronic bronchitis) and increasing stickiness thereof. Because of a thick and compact mucus cover the drug cannot get under it and react with receptors.
  • a combined therapy is applied where the drag is administered by inhalation, in combination with oral administration of mucolytics for thinning the mucus.
  • a bioactive preparation in form of powder and a method of its manufacturing is known from a patent specification PL195212, which describes method of manufacturing of particles for administering bioactive substance into a patient's respiratory tract.
  • the particles can be administered as dry powders or in form of a stabilized dispersion containing non-aqueous continuous phase.
  • Particularly advantageous is to deliver the particles by using a dry powder inhaler, metered-dose inhaler or a nebulizer.
  • a pharmaceutical preparation containing insoluble active ingredient is known from a patent specification PL378270, describing a pharmaceutical preparation for intrapulmonary administration, in form of particles containing a fraction of active ingredient in a lipid matrix, where solubility of the active ingredient in water is below 1.0 mg/ml.
  • the diameter of at least 90% of active ingredient particles in the pharmaceutical preparation is below 3 ⁇ m.
  • the insoluble active ingredient is amfotericin B.
  • the diameter and shape of particles can be such as to easy deliver the pharmaceutical preparation in aerosol form deep into lungs.
  • compositions containing active particles containing active ingredient manufactured by following steps: providing of emulsion where dispersed phase contains solution of active ingredient in a solvent, and inducing formation of solid particles containing active ingredient in the emulsion.
  • the particles can be separated from the emulsion.
  • the invention also refers to active particles having standardized kurtosis not less than 5 and median diameter less than 100 ⁇ m.
  • Powder for application in a dry powder inhaler composition of a carrier particle and a method of such carrier manufacturing are known from a patent specification PL196951.
  • the powder for use in a dry powder inhaler consists of an active ingredient and a carrier, where lubricant percentage in the carrier ranges from 0.05 to 0.5% w/w, and carrier particles are at least partially coated with lubricant particles.
  • the composite carrier for powdered drugs according to the present invention consists in that the composite carrier is in form of particles permanently bound into aggregates containing mucolytic substances and surfactants in the structure.
  • the carrier particle is microporous, with particularly developed surface defects.
  • the active ingredient, permanently bound by carrier particles has the aerodynamic diameter smaller than 5 ⁇ m.
  • the mucolytic substance incorporated in the particle structure is in liquid or solid form under standard conditions at the temperature of 25 0 C and under pressure of 1 arm.
  • mucolytic substances are contained in the carrier particle structure, and are incorporated into the carrier structure in form of solid phase, preferably crystalline; and furthermore, the specific volume of the mucolytic substance is different from the specific volume of the carrier material.
  • surfactant is introduced into a volume structure of the carrier composite and also adsorbed on the surface of that structure.
  • Surfactant is introduced into a volume solution of the carrier composite in the solvent and then adsorbed on the surface of the interface between solution and surrounding gas phase when the droplet of the solution is formed.
  • quantities of the mucolytic substance and the surfactant that are introduced into the carrier particle structure are sufficient to activate the drug transport process within a deposition area covering at least 1 mm 2 of mucus surface.
  • the carrier particle structure diameter may be below 3.5 ⁇ m.
  • the drag composite carrier Preferably all constituents of the drag composite carrier are water- soluble.
  • the carrier particle contains lactose.
  • mannitol is used as a mucolytic substance.
  • dipalmitoylphosphatidylcholine DPPC
  • DPPC dipalmitoylphosphatidylcholine
  • the drug carrier manufacturing method according to the invention consists in that the composite carrier particles are manufactured from a solution of the composite constituents, by atomization of the solution to the form of droplets, followed by controlled evaporation of the solvent, and segregation of dried particles.
  • the solution of substances that are the composite constituents is a solution of a main substance, mucolytic substance and surfactant in a volatile solvent, where such solvent is common for all dissolved constituents.
  • the solution is atomized to droplets of initial diameters not greater than 30 ⁇ m.
  • droplets of solution are formed by pneumatic or ultrasonic method.
  • solvent evaporates whilst droplets pass through a multi- step drying system preset for a particular temperature profile.
  • solvent evaporates in a multi-step drying system, with controlled heating zones, and preset for a particular temperature profile, in a spray-drying process, where the temperature at the inlet to the system is at least 1O 0 C higher than the solvent boiling point, and the temperature in exit section of the drying system is at least 1O 0 C lower than the solvent boiling point.
  • carrier particles during the spray-drying process acquire the carrier particles of expanded surface structure due to microcracks of the solid phase are formed.
  • the dried particles on leaving the air flow drying system enter a pre-separation system, where non-respirable fraction of powder particles greater in size than 5 ⁇ m is separated; then the remaining fraction of particles smaller than 5 ⁇ m is separated in a respirable fraction separation system, and the separated powder is received from a collector as a final product.
  • dried particles of the composite carrier are obtained from a water solution containing lactose as a main component, mannitol as mucolytic substance, and dipalmitoylphosphatidylcholine (DPPC) as surfactant.
  • DPPC dipalmitoylphosphatidylcholine
  • the plant according to the invention consists in that the plant is provided with a system for generation of a liquid aerosol from a multicomponent solution/suspension, then a multi step drying system with controlled heating zones, and after that a system for pre-separation of non- respirable fraction of powder particles.
  • aerosol generation system is a pneumatic atomization system.
  • the aerosol generation system is a ultrasonic generation system.
  • the non-respirable powder fraction pre-separation system is an inertial dust collector.
  • the respirable fraction separation system is a high- performance dedusting system for extraction of particles of aerodynamic diameter below 5 ⁇ m.
  • the composite carrier for powdery drugs according to the invention is distinguished by the particle diameter that corresponds to the size of particles from the respirable fraction, delivered to the respiratory system by inhalation.
  • the composite drug carrier improves drug penetration through a mucus layer once the particle has been deposited on the surface of the respiratory tract.
  • This diameter may be adjusted by selecting the concentration of active substances in the water solution from which the primary droplets are generated, and then in the process of drying solid particles.
  • the particle diameter may be also adjusted by selecting a method of the solution atomization.
  • adoption of a suitable temperature profile in the drying system allows for obtaining of particles of microporoiis structure, what results in apparent density of the composite material below 0,8 g/cm 3 .
  • the surface structure of particles is adjusted be by selection of the solution composition and the temperature profile in the drying process. As a result particles showing low tendency to aggregate are obtained what makes their aerosolization easier.
  • the plant for manufacturing composite carrier particles is presented at the drawing, where 1 is a system for liquid aerosol generation from a multicomponent solution/suspension, 2 is a multi-step drying system with controlled heating zones, 3 is a system for preseparation of a non-respirable fraction of powder particles, and 4 is a respirable fraction separation system.
  • a composite carrier for powdery drugs contains the active ingredient administered by inhalation in form of particles permanently bound in aggregates with particles of the composite carrier containing mucolytics (mucolytic substances) and surfactants in its structure.
  • the carrier particle is microporous, with particularly developed surface defects, its aerodynamic diameter is less than 5 ⁇ m.
  • Mucolytic substance, embedded in the particle structure is in liquid state under standard conditions at the temperature of 25 0 C and under pressure of 1 atm, whereas surfactant is introduced into a volume structure of the carrier composite and also adsorbed on the surface of that structure during the process of spray drying.
  • quantities of the mucolytic substance and the surfactant that are introduced into the carrier particle structure are sufficient to activate the drug transport process within a deposition area covering at least 1 mm 2 of mucus surface, while all constituents of the drug composite carrier are water-soluble.
  • a composite carrier for powdery drugs prepared as described under Example 1, except that the carrier particle contains mucolytic substances in its structure; the mucolytic substances are embedded in the structure, and under standard conditions at the temperature of 25 0 C and under pressure of 1 atm they occur in form of solid, crystalline phase, and furthermore, the specific volume of the mucolytic substance is different from the specific volume of the carrier material.
  • a composite carrier for powdery drugs prepared as described under Example 1, except that the carrier particle containing lactose, has in its structure mucolytic substances in form of non-ionic osmotic agent rnannitol, and surfactant which is a chemical compound dipalmitoylphosphatidylcholine (DPPC).
  • DPPC dipalmitoylphosphatidylcholine
  • the surface activity of surfactant combined with lactose is greater than the activity of a pure surfactant.
  • changes produced by the action of mannitol from the new composite particle, in viscosity of 0.1% mucin solution were measured, the mucin solution was assumed as bronchial mucus reference standard. It follows from the obtained results that mannitol in quantity of 0.05 ing per 1 g of the mucus standard reduces its viscosity more than three times.
  • a composite particle, containing a carrier in form of lactose, with added surfactant (DPPC) and mucolytic substance (mannitol), obtained by the new method has a diameter corresponding to the respirable fraction - in terms of size of particles delivered into the respiratory system by inhalation.
  • the diameter may be adjusted by selection of concentrations of active ingredients in the water solution, from which the primary droplets are generated, and then in the drying process of the solid particle.
  • the obtained particles may get microporoiis structure, and the apparent density of the composite material is smaller than 0.8 g/cm 3 .
  • composite material obtained in such a way shows advantageous properties: it liquefies mucus and is surface-active, what activates transport of a drug particle attached to the carrier particle under the mucus surface and thus intensifies therapeutic effects.
  • the drag carrier manufacturing method consists in that the composite carrier particles are obtained from a solution containing a main substance, mucolytic and surfactant in volatile solvent, common for all dissolved constituents, in the process of the solution atomization to the droplets of diameters initially not greater than 30 ⁇ m and the said droplets are formed from the solution by pneumatic method in the liquid aerosol generation system 1.
  • Solvent evaporates whilst droplets pass through the multi step drying system 2 , with controlled heating zones, and preset for a particular temperature profile, in a spray-drying process, where the temperature at the inlet to the oven is at least 1O 0 C higher than the solvent boiling point, and the temperature in the exit zone of the oven is at least 1O 0 C lower than the solvent boiling point.
  • the dried particles are separated in the non-respirable fraction pre-separation system 3, where a fraction of powder particles greater in size than 5 ⁇ m is separated; and the remaining fraction of particles smaller than 5 ⁇ m, having passed through the respirable fraction separation system 4, is received from a collector as a final product.
  • Example 6 The drug carrier manufacturing is carried out as described in Example 4, except that the droplets of solution are formed in the liquid aerosol generation system 1 by ultrasonic method, and that the carrier particles formed during the spray-drying process in the multi step drying system 2 and provided with controlled heating zones, are characterized by expanded surface structure, due to microcracks of the solid phase.
  • Example 6
  • the drug carrier manufacturing is carried out as described in Example 4 or Example 5, except that the drug carrier particles are obtained from a water solution containing lactose as a main component, at amount of 0.07 g per 1 ml of water, non-ionic osmotic agent mannitol as mucolytic, at amount of 0.06 g per 1 ml of water, to reduce mucus viscosity, and dipalmitoylphosphatidylcholine (DPPC) as surfactant, at amount of 0.05 mg per 1 ml of water.
  • DPPC dipalmitoylphosphatidylcholine
  • the solution is atomized to droplets in the liquid aerosol generation system 1, which is an ultrasonic generator of vibration frequency of 2.5 MHz, then the droplets are dried in the multi step drying system 2, which is a pipe oven with temperatures preset downstream to: 15O 0 C, 100 0 C and 8O 0 C, respectively.
  • Particles of an average mass diameter below 3.5 ⁇ in are obtained in a respirable fraction separation system 4. Microscopic observations proved that the particles have a porous, morphologically developed microstructure, of apparent density 0.8 g/cm 3 .
  • a plant for manufacturing composite carrier particles comprises: a system 1 for liquid aerosol generation from a multicomponent solution/suspension, followed by a multi step drying system 2 with controlled heating zones, a system 3 for pre-separation of a non-respirable fraction of powder particles, and a respirable fraction separation system 4.
  • a liquid aerosol in form of a mist composed of droplets suspended in air is produced from a multicomponent solution or suspension of carrier and active substances in a suitable solvent, in a system of aerosol generation 1, operating on a pneumatic, ultrasonic or other principle of atomization.
  • a jet of fresh, cleaned and dried air flows in the generation system 1.
  • the generated mist enters the drying system 2, where heating zones of different temperatures allow for precise control of the crystallization process that proceeds as a result of the solvent evaporation from the droplets.
  • the obtained dry powder aerosol leaves the drying system 2, and undergoes a separation - first in the non-respirable fraction pre- separation system 3, and then - in the respirable fraction separation system 4.
  • the pre-separator 3 can be an inertial dust collector, used for separation of particles having diameters out of the respirable limits, i.e. greater than 5 ⁇ m, whereas the respirable fraction separation system 4 is a high-performance dedusting system, for separation of particles smaller than 5 ⁇ m, that are a desired product used as a powder for inhalation. After the powder separation, the air jet flows out from the respirable fraction separation system 4, to the outside of the plant.
  • the enhanced effectiveness of the composite carrier in comparison to the lactose particles is connected with the fact that molecules DPPC associated with lactose are in their surface area oriented with the hydroxycarbon chains to the outside of the particle. As the result we can observe hindering effect.
  • the particles of the composite carrier do not stick to each other and may be easily entrained. These effect does not occur in relation to the porous particles known from the prior art.

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

Abstract

La présente invention concerne un support composite pour médicaments pulvérulents qui se traduit par une particule de support liée de manière permanente à une particule de médicament, où le support composite est sous la forme de particules liées de manière permanente en agrégats contenant des mucolytiques et des surfactants dans sa structure. Le procédé de fabrication du support de médicament consiste en ce que les particules de support composite sont fabriquées à partir d'une solution des constituants composites, par atomisation de la solution sous la forme de gouttelettes, suivie d'une évaporation contrôlée du solvant, et de la ségrégation des particules sèches. L'équipement pour la fabrication des particules de support est muni d'un système (1) pour la génération d'aérosol liquide à partir d'une solution/suspension, suivi d'un système de séchage à plusieurs étapes (2) avec des zones de chauffage contrôlées, d'un système (3) pour la pré-séparation d'une fraction non respirable des particules de poudre et d'un système de séparation (4) de la fraction respirable.
EP09735696A 2008-04-21 2009-04-20 Support composite pour médicaments pulvérulents, procédé de fabrication du support et équipement pour la fabrication des particules de support composite Ceased EP2278959A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP11150820A EP2340816A1 (fr) 2008-04-21 2009-04-20 Installation pour la fabrication de particules support composites
EP11150815A EP2340817A1 (fr) 2008-04-21 2009-04-20 Procédé de production d'un support de médicament

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PL384984A PL220269B1 (pl) 2008-04-21 2008-04-21 Kompozytowy nośnik leków proszkowych, sposób wytwarzania nośnika leków oraz urządzenie do wytwarzania cząstek nośnika kompozytowego
PCT/PL2009/000036 WO2009131473A2 (fr) 2008-04-21 2009-04-20 Support composite pour médicaments pulvérulents, procédé de fabrication du support et équipement pour la fabrication des particules de support composite

Publications (1)

Publication Number Publication Date
EP2278959A2 true EP2278959A2 (fr) 2011-02-02

Family

ID=40940506

Family Applications (3)

Application Number Title Priority Date Filing Date
EP11150815A Withdrawn EP2340817A1 (fr) 2008-04-21 2009-04-20 Procédé de production d'un support de médicament
EP11150820A Withdrawn EP2340816A1 (fr) 2008-04-21 2009-04-20 Installation pour la fabrication de particules support composites
EP09735696A Ceased EP2278959A2 (fr) 2008-04-21 2009-04-20 Support composite pour médicaments pulvérulents, procédé de fabrication du support et équipement pour la fabrication des particules de support composite

Family Applications Before (2)

Application Number Title Priority Date Filing Date
EP11150815A Withdrawn EP2340817A1 (fr) 2008-04-21 2009-04-20 Procédé de production d'un support de médicament
EP11150820A Withdrawn EP2340816A1 (fr) 2008-04-21 2009-04-20 Installation pour la fabrication de particules support composites

Country Status (3)

Country Link
EP (3) EP2340817A1 (fr)
PL (1) PL220269B1 (fr)
WO (1) WO2009131473A2 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108295361B (zh) * 2018-02-23 2023-10-03 北京东方金荣超声电器有限公司 一种药物球囊涂药设备

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US5698537A (en) * 1996-06-18 1997-12-16 Clarion Pharmaceuticals Inc. Method of lowering the viscosity of mucus
KR100575070B1 (ko) 1997-09-29 2006-05-03 넥타르 테라퓨틱스 안정화된 생활성 제제 및 이의 사용 방법
AU780327B2 (en) * 1999-06-30 2005-03-17 Novartis Ag Spray drying process for preparing dry powders
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GB0008411D0 (en) 2000-04-05 2000-05-24 Vectura Ltd Pharmaceutical preparations and their manufacture
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Title
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Also Published As

Publication number Publication date
WO2009131473A8 (fr) 2011-04-28
EP2340817A1 (fr) 2011-07-06
WO2009131473A3 (fr) 2009-12-23
EP2340816A1 (fr) 2011-07-06
PL220269B1 (pl) 2015-09-30
WO2009131473A2 (fr) 2009-10-29

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