WO2011037549A2 - Dry powder formulation of tiotropium carried in blister strip - Google Patents

Dry powder formulation of tiotropium carried in blister strip Download PDF

Info

Publication number
WO2011037549A2
WO2011037549A2 PCT/TR2010/000183 TR2010000183W WO2011037549A2 WO 2011037549 A2 WO2011037549 A2 WO 2011037549A2 TR 2010000183 W TR2010000183 W TR 2010000183W WO 2011037549 A2 WO2011037549 A2 WO 2011037549A2
Authority
WO
WIPO (PCT)
Prior art keywords
dry powder
medicament formulation
powder form
tiotropium
blister
Prior art date
Application number
PCT/TR2010/000183
Other languages
French (fr)
Other versions
WO2011037549A3 (en
Inventor
Bilgic Mahmut
Original Assignee
Bilgic Mahmut
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=43796421&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2011037549(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bilgic Mahmut filed Critical Bilgic Mahmut
Priority to EP10773176.2A priority Critical patent/EP2480203B1/en
Publication of WO2011037549A2 publication Critical patent/WO2011037549A2/en
Publication of WO2011037549A3 publication Critical patent/WO2011037549A3/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
    • A61M15/0043—Non-destructive separation of the package, e.g. peeling
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
    • A61M15/0046—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier
    • A61M15/0051—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier the dosages being arranged on a tape, e.g. strips
    • 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
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/06—Solids
    • A61M2202/064—Powder

Definitions

  • the present invention relates to a method for providing effective inhalation for the treatmenl of respiratory diseases, in which the medicament formulation containing tiotropium, which is in dry powder form, is delivered to the lungs from blisters arranged adjacently in a peelabk blister strip.
  • Tiotropium (Formula I) is an anticholinergic agent with chemical name (1 ⁇ ,2 ⁇ ,4 ⁇ ,7 ⁇ )- 7- [(hydroxidi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0 2,4 ]nonane.
  • Tiotropium is described in European patent application numbered EP0418716 for the firs time.
  • processes for preparing tiotropium, pharmaceutica compositions containing tiotropium, long-acting, strong anticholinergic activity of tiotropiun and use of it in the treatment of respiratory disorders are defined.
  • Tiotropium is a commonly preferred anticholinergic, because of showing long-acting action for the treatment of respiratory disorders especially chronic disorders such as asthma and chronic obstructive pulmonary disorder (COPD) which threaten the society widely.
  • the inhalation product for the treatment of these disorders is sold by Boehringer and Pfizer under the trade name Spiriva® Handihaler®. This product contains Handihaler® which is a single- dose inhaler and Spiriva® which contains dry powder formulation of tiotropium bromide monohydrate and consists of single dose dry powder inhaler capsules used only in the Handihaler®.
  • This drug which is administered via inhalation route is given in lower doses compared to the the drug given via oral and parenteral route, and shows desired effect and less side-effects.
  • Gastrointestinal disturbances such as low resolution, low permeability, drug irritation, production of undesired metabolites and decrease of bioavailability depending on food, which are change the effectiveness of the drug, are felt in minimum level because of the fact that the drugs administered via inhalation route, reach directly to target area and do noi get into circulation of blood.
  • the mechanical components such as needles that are contained in a single dose dr powder inhalers with capsule are used for piercing capsule. These may become blunt or los ⁇ certain position over time. Thus, an efficient piercing can not be achieved. Since this reduce the rate of utilization of the dry powder formulation in the capsule, effective amount of the dry powder formulation is not delivered to the lungs. Additionally, there is a risk of inhaling the plastic parts of the capsule which stick to the edge of piercing components of the inhalei during the piercing operation.
  • inhalation of the dry powder formulation from the capsule there are different inhalation methods such as the inhalation of a formulation containing one or more active substances from the metered dose inhalers, the nebulizers or the dry powder inhalei containing blister packs pierced just before inhalation.
  • Nebulization and aerosol formulations contain the active substances in liquid form. It is more difficult to provide stability and dose accuracy in liquid form formulations compared to the dry powder formulations.
  • the blistei packs pierced just before inhalation suffer from some drawbacks which are caused by the piercing components in the multi dose dry powder inhalers as mentioned before.
  • the metered dose inhaler requires the mechanical components to be contained in this inhale] for an effective and sufficient inhalation of the dry powder formulation from the reservoir
  • these mechanic components cause increase in the size and weight of the inhaler anc difficulty of use.
  • problems caused by the formulatior being in the liquid form and piercing operation of the capsule or a blister pack in the inhaler lead to drawbacks related to the stability and as a result of that reliability of the dn3 ⁇ 4 formulation.
  • the present invention provides the dry powder formulation which contain: tiotropium and is inhaled from the blisters of the peelable blister strip. In another aspect, the present invention provides the dry powder formulation which contains tiotropium and inhaled by providing controlled dosing of the dry powder formulation in an effective and stable way.
  • the present invention provides the dry powder formulation which contains tiotropium and is inhaled in an effective, hygienic, user-friendly way.
  • the present invention provides a method for inhaling the dry powdei formulation, in which the dry powder formulation containing tiotropium is inhaled from the blisters of the peelable blister strip.
  • the present invention provides the medicament formulation which contains tiotropium and is inhaled from a multi-dose inhaler.
  • the medicament formulation in accordance with the present invention contains optionally one or more excipients.
  • excipient used in said dry powder formulation can be selected from the group comprising monosaccharides, disaccharides, polysaccharides, and oligosaccharides.
  • lactose is used.
  • said dry powder formulation contains the excipient in an amounl in the range of 0 to 50 mg.
  • the cavity volume of the blisters of the blister strip which cany and store said dry powder formulation containing tiotropium, is in the range of 20 to 30 mm . preferably in the range of 21 to 25 mm , most preferably in the range of 22-23 mm .
  • the blister strip which consists of blisters which have a cavity volume in the range of 22 to 23 mm preferably in the range of 21 to 25 mm , most preferabl) in the range of 22-23 mm 3 , is used for providing efficient inhalation by dealing with the drawbacks defined herein before. Additionally, each blister cavity having the volume described above is filled up to 25-100 %, preferably up to 70-100 %, most preferably up tc 90-100 % of the said volume.
  • the peelable blister strip wherein the blisters are arranged adjacently consists of a lid sheel and a base sheet which are closed very tightly to provide impermeability by using any suitable method.
  • the lid sheet and the base sheet of the peelable blister strip consists of many layers such as polymeric layer, aluminum foil and optionally Aclar® fiuoropolimer film.
  • Aclar® fluoropolimer film is between the layers which make up the lid sheet and the base sheet of the blister strip.
  • Aclar® fluoropolymer film is a polymeric film which is used for production of the blister strip and provides high moisture protection. This chemically inert film does not cause any change in taste of the formulation when it is in contact with the dry powder formulation. It easily forms a lamellar structure with other polymeric layers which are made from various polymers. It is suitable for treatment with heat.
  • Desiccant agents are optionally added to the polymeric layers in order to reduce moisture and gas permeability of the polymeric layers for protection of stability of the dry powdei formulation contained in the blisters which are arranged adjacently.
  • Some examples of the desiccant agents are silica gel, zeolite, alumina, baucsite, anhydrous calcium sulfate, activated carbon, clay capable of absorbing water.
  • aluminium foil is used both in the lid sheet and in the base sheel of the peelable blister strip to provide high humidity and gas protection because of thai aluminium foil is conventionally used in both the lid sheet and the base sheet of the blistei strip for high humidty and gas protection.
  • These layers must have the sufficient thickness which provides the protection for the stability of humidity sensitive dry powder formulation which is stored in blister cavity. Because of this reason, the thickness of aluminium foil that is used in the lid sheet and the base sheet of the blister strip is in the range of 10 to 40 ⁇ . preferably of 15 to 30 ⁇ .
  • the polymeric layers which are contained in the lid sheet and the base sheet of the peelable blister strip in accordance with the present invention may be made from either same oi different polymers.
  • the thickness of these polymeric layers depends on the type of polymeric substance used and its properties. Therefore, the thickness of each polymeric layer which is used in the lid sheet and the base sheet of said blister strip is in the range of 15 to 60 ⁇ . preferably of 20 to 35 ⁇ depending on the type of polymer used.
  • the inside layer of blister cavity of said blister strip which is in contact with dry powdei formulation is polymeric layer because of the fact that aluminium foil causes adhesion of z part of dry powder formulation to inside layer of the cavity due to electrostatic forces, and hence cause uncontrolled dosing.
  • the polymers used for forming polymeric layers are preferably selected from a group comprising thermo-plastic polymers such as polyethylene, polypropylene, polystyrene, polyolefin, polyamide, polyvinyl chloride, polyurethane.
  • said blisters which placed in the peelable blister strips can be in any shape undei the condition that mentioned above.
  • Said dry powder formulation which contains tiotropium is decomposed by an amount of 3°A with respect to the total weight of the formulation after 16 months under the condition thai said dry powder formulation is stored in the blisters of the peelable blister strip, in the temperature of 25°C and in the relative humidity (RH) of %60.
  • the active agents which is contained in the medicament formulation is tiotropium and it is selected from a group comprising its pharmaceutically acceptable salts, solvates and/or hydrates thereof. According to the invention, it is preferably tiotropium bromide anhydrate.
  • the medicament formulation which is in drj powder form contains the active agents with the particle size of less than 20 ⁇ . Lactose i: used as excipient. The excipients with fine and coarser particles which have different partic size range, are used in order to provide effective inhalation of the medicament formulation.
  • said dry powder formulation contains tiotropium o: pharmaceutically acceptable salts which is present in the range of 1 to 50 ⁇ g in each blister o the peelable blister strip.
  • the medicament formulation in accordance with present invention can be used for the treatment of many respiratory diseases such as asthma, chronic obstructive pulmonary disorder (COPD) and allergic rhinitis. Accordingly, the respiratory diseases include but are not restricted to allergic or non-allergic asthma in various phases, acute lung injury (ALI).
  • ARDS acute respiratory distress syndrome
  • COPD chronic obstructive pulmonary
  • COAD oi COLD chronic obstructive pulmonary
  • emphysema and chronic bronchitis pneumoconiosis, aluminosis anthracosis, asbestosis, chalicosis, ptilosis, siderosis, silicosis, tabacosis and byssinosis.
  • the treatment of said diseases may be prophylactic or symptomatic.
  • the medicament composition in accordance with the present invention is used especially for the symptomatic treatment of asthma, allergic rhinitis and COPD.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pulmonology (AREA)
  • Chemical & Material Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Otolaryngology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to a method for providing effective inhalation for the treatment of respiratory diseases, in which the medicament formulation containing tiotropium, which is in dry powder form and is delivered to the lungs from blisters arranged adjacently in a peelable blister strip.

Description

DRY POWDER FORMULATION OF TIOTROPIUM CARRIED IN BLISTER STRIP
DESCRIPTION
The present invention relates to a method for providing effective inhalation for the treatmenl of respiratory diseases, in which the medicament formulation containing tiotropium, which is in dry powder form, is delivered to the lungs from blisters arranged adjacently in a peelabk blister strip.
Tiotropium (Formula I) is an anticholinergic agent with chemical name (1α,2β,4β,7β)- 7- [(hydroxidi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane.
Figure imgf000002_0001
Tiotropium is described in European patent application numbered EP0418716 for the firs time. In this patent document; processes for preparing tiotropium, pharmaceutica compositions containing tiotropium, long-acting, strong anticholinergic activity of tiotropiun and use of it in the treatment of respiratory disorders, are defined.
Tiotropium antagonises effect of acetylcholine via blocking cholinergic muscarinic receptoi Tiotropium is separated slowly from Ml and M3 receptors that cause broncho-construction and it is separated rapidly from M2 receptors that inhibit release of acetylcholine fron cholinergic nerve endings. This situation occurred in lung receptors demonstrates long actinj bronchodilator activity of the drug. Additionally, tiotropium is a long-acting, strong, anticholinergic bronchodilator which is administered orally for the treatment of respiratory disorders.
Tiotropium is a commonly preferred anticholinergic, because of showing long-acting action for the treatment of respiratory disorders especially chronic disorders such as asthma and chronic obstructive pulmonary disorder (COPD) which threaten the society widely. The inhalation product for the treatment of these disorders is sold by Boehringer and Pfizer under the trade name Spiriva® Handihaler®. This product contains Handihaler® which is a single- dose inhaler and Spiriva® which contains dry powder formulation of tiotropium bromide monohydrate and consists of single dose dry powder inhaler capsules used only in the Handihaler®. This drug which is administered via inhalation route is given in lower doses compared to the the drug given via oral and parenteral route, and shows desired effect and less side-effects. Gastrointestinal disturbances, such as low resolution, low permeability, drug irritation, production of undesired metabolites and decrease of bioavailability depending on food, which are change the effectiveness of the drug, are felt in minimum level because of the fact that the drugs administered via inhalation route, reach directly to target area and do noi get into circulation of blood.
Nevertheless, just before every inhalation, one capsule should be taken out of the blister pack and loaded to capsule chamber of a single dose dry powder inhaler. Since the capsule can be loaded into the capsule chamber in a non-hygienic way, there is a risk of inhaling foreigr matters.
Additionally, maintaining the stability and preventing the agglomeration of dry powdei formulation which is contained in a capsule that is prepared for use in a single dose drj powder inhaler in order to achieve an effective inhalation should be considered. Hence, th( capsules, which are convenient for use in a single dose inhaler are carried in a blister pack t( provide a secondary protection for maintaining the stability of the dry powder formulation ii the capsule. This reduces the moisture transition significantly. Even though this methoc solves the problem of maintaining stability of the dry powder formulation, it is not cost effective.
Moreover, the mechanical components, such as needles that are contained in a single dose dr powder inhalers with capsule are used for piercing capsule. These may become blunt or los< certain position over time. Thus, an efficient piercing can not be achieved. Since this reduce the rate of utilization of the dry powder formulation in the capsule, effective amount of the dry powder formulation is not delivered to the lungs. Additionally, there is a risk of inhaling the plastic parts of the capsule which stick to the edge of piercing components of the inhalei during the piercing operation.
As an alternative to the inhalation of the dry powder formulation from the capsule, there are different inhalation methods such as the inhalation of a formulation containing one or more active substances from the metered dose inhalers, the nebulizers or the dry powder inhalei containing blister packs pierced just before inhalation. Nebulization and aerosol formulations contain the active substances in liquid form. It is more difficult to provide stability and dose accuracy in liquid form formulations compared to the dry powder formulations. The blistei packs pierced just before inhalation suffer from some drawbacks which are caused by the piercing components in the multi dose dry powder inhalers as mentioned before. Additionally the metered dose inhaler requires the mechanical components to be contained in this inhale] for an effective and sufficient inhalation of the dry powder formulation from the reservoir Thus, these mechanic components cause increase in the size and weight of the inhaler anc difficulty of use. Furthermore, in all of these methods, problems caused by the formulatior being in the liquid form and piercing operation of the capsule or a blister pack in the inhaler lead to drawbacks related to the stability and as a result of that reliability of the dn¾ formulation.
Because of the above mentioned reasons, there is a need to develop a method which provide; the inhalation of the dry powder formulation containing tiotropium to provide controllec dosing of the dry powder formulation and maintain the stability of the dry powder formulatioi in an user-friendly, hygenic, cost effective way. Suprisingly, the inventor has found that the dry powder formulation which contain: tiotropium, is inhaled effectively from the blisters which are arranged adjacently on a peelabh blister strip and meets the requirements mentioned above.
In one aspect, the present invention provides the dry powder formulation which contain: tiotropium and is inhaled from the blisters of the peelable blister strip. In another aspect, the present invention provides the dry powder formulation which contains tiotropium and inhaled by providing controlled dosing of the dry powder formulation in an effective and stable way.
In another aspect, the present invention provides the dry powder formulation which contains tiotropium and is inhaled in an effective, hygienic, user-friendly way.
In another aspect, the present invention provides a method for inhaling the dry powdei formulation, in which the dry powder formulation containing tiotropium is inhaled from the blisters of the peelable blister strip.
In another aspect, the present invention provides the medicament formulation which contains tiotropium and is inhaled from a multi-dose inhaler.
The medicament formulation in accordance with the present invention contains optionally one or more excipients.
According to the invention, excipient used in said dry powder formulation can be selected from the group comprising monosaccharides, disaccharides, polysaccharides, and oligosaccharides. Preferably lactose is used.
According to the invention, said dry powder formulation contains the excipient in an amounl in the range of 0 to 50 mg.
According to the invention, the cavity volume of the blisters of the blister strip, which cany and store said dry powder formulation containing tiotropium, is in the range of 20 to 30 mm . preferably in the range of 21 to 25 mm , most preferably in the range of 22-23 mm .
According to the invention, the blister strip which consists of blisters which have a cavity volume in the range of 22 to 23 mm preferably in the range of 21 to 25 mm , most preferabl) in the range of 22-23 mm3, is used for providing efficient inhalation by dealing with the drawbacks defined herein before. Additionally, each blister cavity having the volume described above is filled up to 25-100 %, preferably up to 70-100 %, most preferably up tc 90-100 % of the said volume. The peelable blister strip wherein the blisters are arranged adjacently consists of a lid sheel and a base sheet which are closed very tightly to provide impermeability by using any suitable method.
The lid sheet and the base sheet of the peelable blister strip, consists of many layers such as polymeric layer, aluminum foil and optionally Aclar® fiuoropolimer film. Preferably, Aclar® fluoropolimer film is between the layers which make up the lid sheet and the base sheet of the blister strip.
Aclar® fluoropolymer film is a polymeric film which is used for production of the blister strip and provides high moisture protection. This chemically inert film does not cause any change in taste of the formulation when it is in contact with the dry powder formulation. It easily forms a lamellar structure with other polymeric layers which are made from various polymers. It is suitable for treatment with heat.
Desiccant agents are optionally added to the polymeric layers in order to reduce moisture and gas permeability of the polymeric layers for protection of stability of the dry powdei formulation contained in the blisters which are arranged adjacently. Some examples of the desiccant agents are silica gel, zeolite, alumina, baucsite, anhydrous calcium sulfate, activated carbon, clay capable of absorbing water.
According to the invention, aluminium foil is used both in the lid sheet and in the base sheel of the peelable blister strip to provide high humidity and gas protection because of thai aluminium foil is conventionally used in both the lid sheet and the base sheet of the blistei strip for high humidty and gas protection. These layers must have the sufficient thickness which provides the protection for the stability of humidity sensitive dry powder formulation which is stored in blister cavity. Because of this reason, the thickness of aluminium foil that is used in the lid sheet and the base sheet of the blister strip is in the range of 10 to 40 μπι. preferably of 15 to 30 μηι.
The polymeric layers which are contained in the lid sheet and the base sheet of the peelable blister strip in accordance with the present invention may be made from either same oi different polymers. The thickness of these polymeric layers depends on the type of polymeric substance used and its properties. Therefore, the thickness of each polymeric layer which is used in the lid sheet and the base sheet of said blister strip is in the range of 15 to 60 μηι. preferably of 20 to 35 μηι depending on the type of polymer used.
The inside layer of blister cavity of said blister strip which is in contact with dry powdei formulation is polymeric layer because of the fact that aluminium foil causes adhesion of z part of dry powder formulation to inside layer of the cavity due to electrostatic forces, and hence cause uncontrolled dosing.
According to the present invention, the polymers used for forming polymeric layers are preferably selected from a group comprising thermo-plastic polymers such as polyethylene, polypropylene, polystyrene, polyolefin, polyamide, polyvinyl chloride, polyurethane. Moreover, said blisters which placed in the peelable blister strips, can be in any shape undei the condition that mentioned above.
Said dry powder formulation which contains tiotropium, is decomposed by an amount of 3°A with respect to the total weight of the formulation after 16 months under the condition thai said dry powder formulation is stored in the blisters of the peelable blister strip, in the temperature of 25°C and in the relative humidity (RH) of %60.
In accordance with the present formulation, the active agents which is contained in the medicament formulation is tiotropium and it is selected from a group comprising its pharmaceutically acceptable salts, solvates and/or hydrates thereof. According to the invention, it is preferably tiotropium bromide anhydrate. Said dry powder form, which is stored in the blister cavities of the peelable blister strip i: produced with methods known in the prior art. The medicament formulation which is in drj powder form, contains the active agents with the particle size of less than 20 μηι. Lactose i: used as excipient. The excipients with fine and coarser particles which have different partic size range, are used in order to provide effective inhalation of the medicament formulation. According to the invention, said dry powder formulation contains tiotropium o: pharmaceutically acceptable salts which is present in the range of 1 to 50 μg in each blister o the peelable blister strip. The medicament formulation in accordance with present invention can be used for the treatment of many respiratory diseases such as asthma, chronic obstructive pulmonary disorder (COPD) and allergic rhinitis. Accordingly, the respiratory diseases include but are not restricted to allergic or non-allergic asthma in various phases, acute lung injury (ALI). acute respiratory distress syndrome (ARDS), exacerbation of airways hyperactivity, bronchiectasis, chronic obstructive pulmonary, airways or lung diseases (COPD, COAD oi COLD) including emphysema and chronic bronchitis, pneumoconiosis, aluminosis anthracosis, asbestosis, chalicosis, ptilosis, siderosis, silicosis, tabacosis and byssinosis. The treatment of said diseases may be prophylactic or symptomatic. In addition to this, the medicament composition in accordance with the present invention is used especially for the symptomatic treatment of asthma, allergic rhinitis and COPD.

Claims

1. A medicament formulation containing tiotropium or its pharmaceutically acceptable sail for the treatment of respiratory disorders is characterized in that:
• said medicament formulation is in dry powder form, and
• said medicament formulation is carried and stored in a peelable blister strip.
2. A medicament formulation according to Claim 1 wherein said medicament formulation comprises optionally one or more pharmaceutically acceptable excipients.
3. A medicament formulation in dry powder form according to claim 2 wherein the excipieni is selected form the group comprising monosaccharides, disaccharides, polysaccharides and oligosaccharides.
4. A medicament formulation in dry powder form according to claim 2 wherein the excipieni is a disaccharide.
5. A medicament formulation in dry powder form according to claim 2 wherein the excipieni is preferably lactose.
6. A medicament formulation in dry powder form according to claim 1 wherein lactose is present in an amount in the range of 0 to 50 μg.
7. A medicament formulation in dry powder form according to claim 1 wherein the active agents have average particle size of less than 20 μπι.
8. A medicament formulation in dry powder form according to claim 1 wherein tiotropium oi pharmaceutically acceptable salts thereof is present in an amount in the range of 1 to 50 μg
9. A medicament formulation in dry powder form according to claim 1 wherein tiotropium oi pharmaceutically acceptable salts thereof is present in an amount in the range of 1 to 50 μ£ and one or more pharmaceutically acceptable excipients which is present in the range of 0 tc 50 μδ.
10. Use of tiotropium or a pharmaceutically acceptable for the preparation of a medicamen formulation in dry powder form according to any of the preceding claims.
11. A medicament formulation in dry powder form according to any one of the preceding claims wherein the active agent is tiotropium, preferably tiotropium bromide anhydrate.
12. A peelable blister strip according to the claim 1 wherein each blister has a cavity volume of 20 to 30 mm and contains said medicament formulation containing tiotropium and one or more excipients in a sufficient amount and is administered by dry powder inhaler.
13. A peelable blister strip according to claim 12 wherein each blister has a cavity volume of
21 to 25 mm and contains said medicament formulation in dry powder form.
14. A peelable blister strip according to claim 12 wherein each blister has a cavity volume of
22 to 23 mm and contains said medicament formulation in dry powder form.
15. A peelable blister strip according to claim 1 wherein each blister cavity is filled up to 25- 100% of the total volume.
16. A peelable blister strip according to claim 1 wherein each blister cavity is is filled up to 70 to 100% of the total volume.
17. A peelable blister strip according to claim 1 wherein each blister cavity is filled up to 90 to 100% of the total volume.
18. A peelable blister according to claim 1 wherein said blister has a lid sheet and a base sheet opened by seperating from each other before inhalation.
19. A base sheet according to claim 18 wherein said base sheet consists of at least one layer comprising a polymeric layer and aluminium foil.
20. A lid sheet according to claim 18 wherein said lid sheet consists of at least one layer comprising a polymeric layer and aluminium foil.
21. A polymeric layer according to any one of the claims 18 to 20 wherein said polymeric layer is present in both the lid sheet and the base sheet of the blister strip and preferably contains a desiccant.
22. A polymeric layer according to claim 21 wherein said polymeric layer, that is present ir the lid sheet and base sheet of the blister strip, is made from a polymeric substance selectee from a group comprising thermoplastics and synthetic polymers.
PCT/TR2010/000183 2009-09-23 2010-09-22 Dry powder formulation of tiotropium carried in blister strip WO2011037549A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP10773176.2A EP2480203B1 (en) 2009-09-23 2010-09-22 Dry powder formulation of tiotropium carried in blister strip

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2009/07236 2009-09-23
TR2009/07236A TR200907236A2 (en) 2009-09-23 2009-09-23 Transport of Tiotropium dry powder formulation in blister pack.

Publications (2)

Publication Number Publication Date
WO2011037549A2 true WO2011037549A2 (en) 2011-03-31
WO2011037549A3 WO2011037549A3 (en) 2011-06-09

Family

ID=43796421

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2010/000183 WO2011037549A2 (en) 2009-09-23 2010-09-22 Dry powder formulation of tiotropium carried in blister strip

Country Status (3)

Country Link
EP (1) EP2480203B1 (en)
TR (1) TR200907236A2 (en)
WO (1) WO2011037549A2 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2480203B1 (en) 2009-09-23 2016-08-24 Mahmut Bilgic Dry powder formulation of tiotropium carried in blister strip
EP2460562B1 (en) 2006-12-21 2016-10-05 Galderma Research & Development Cream-gel comprising at least one retinoid and benzoyl peroxide
US9737518B2 (en) 2013-04-01 2017-08-22 Pulmatrix Operating Company, Inc. Tiotropium dry powders
US20210069106A1 (en) * 2018-01-26 2021-03-11 Novartis Ag High dose delivery of inhaled therapeutics

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0418716A1 (en) 1989-09-16 1991-03-27 Boehringer Ingelheim Kg Thienylcarboxylic acid ester of aminoalcohols, their quaternary products, their preparation and use of the compounds

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE9400462D0 (en) 1994-02-11 1994-02-11 Astra Ab Filling device
CH689305A5 (en) * 1994-08-23 1999-02-15 Alusuisse Lonza Services Ag Blister.
GB9902689D0 (en) * 1999-02-08 1999-03-31 Novartis Ag Organic compounds
US6608055B2 (en) 2001-06-22 2003-08-19 Boehringer Ingelheim Pharma Kg Crystalline anticholinergic, processes for preparing it and its use for preparing a pharmaceutical composition
GB0217196D0 (en) * 2002-07-25 2002-09-04 Glaxo Group Ltd Medicament dispenser
GB0225621D0 (en) 2002-11-02 2002-12-11 Glaxo Group Ltd Medicament carrier
SE527190C2 (en) * 2003-06-19 2006-01-17 Microdrug Ag Administration of metered dry powder combined doses of finely divided dry medication powders involves selecting first and second medicaments for forming of pharmaceutical, combined doses
EP1691782A1 (en) * 2003-12-03 2006-08-23 Microdrug AG Medical product containing tiotropium
SE0303569L (en) * 2003-12-03 2005-06-04 Microdrug Ag DPI for delivery of moisture-sensitive drugs
US6945581B2 (en) 2003-12-08 2005-09-20 Lear Corporation Integral lighting for consoles
GB0427856D0 (en) 2004-12-20 2005-01-19 Glaxo Group Ltd Maniflod for use in medicament dispenser
DE102005035705A1 (en) * 2005-07-27 2007-02-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg pharmaceutical blister
GB0515584D0 (en) * 2005-07-28 2005-09-07 Glaxo Group Ltd Medicament dispenser
EP2327403A3 (en) * 2007-02-19 2011-08-31 Cipla Limited Pharmaceutical combinations of at least two bronchodilators
TR200907236A2 (en) 2009-09-23 2011-04-21 Bi̇lgi̇ç Mahmut Transport of Tiotropium dry powder formulation in blister pack.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0418716A1 (en) 1989-09-16 1991-03-27 Boehringer Ingelheim Kg Thienylcarboxylic acid ester of aminoalcohols, their quaternary products, their preparation and use of the compounds

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2460562B1 (en) 2006-12-21 2016-10-05 Galderma Research & Development Cream-gel comprising at least one retinoid and benzoyl peroxide
EP2480203B1 (en) 2009-09-23 2016-08-24 Mahmut Bilgic Dry powder formulation of tiotropium carried in blister strip
US9737518B2 (en) 2013-04-01 2017-08-22 Pulmatrix Operating Company, Inc. Tiotropium dry powders
US20210069106A1 (en) * 2018-01-26 2021-03-11 Novartis Ag High dose delivery of inhaled therapeutics

Also Published As

Publication number Publication date
EP2480203A2 (en) 2012-08-01
WO2011037549A3 (en) 2011-06-09
EP2480203B1 (en) 2016-08-24
TR200907236A2 (en) 2011-04-21

Similar Documents

Publication Publication Date Title
EP2528585B1 (en) Pharmaceutical compositions comprising tiotropium, formoterol and budesonide
EP2528596B1 (en) Dry powder formulations administered by the inhalation route comprising a combination of tiotropium bromide, salmeterol xynafoate and fluticasone propionate.
EP2533777B1 (en) Pharmaceutical compositions comprising fluticasone, tiotropium and sodium cromoglycate
WO2011093819A2 (en) New combination comprising tiotropium
WO2011093820A2 (en) A pharmaceutical combination comprising tiotropium
EP2480203B1 (en) Dry powder formulation of tiotropium carried in blister strip
WO2013109210A1 (en) Dry powder formulations comprising budesonide
WO2013009271A1 (en) New improved dry powder formulation
EP2515888B1 (en) Dry powder formulation containing tiotropium for inhalation
EP2804590A1 (en) Dry powder formulations comprising tiotropium and carmoterol
EP2480202B1 (en) Carrying of a combination containing tiotropium in a blister strip
EP2515848B1 (en) Dry powder combination of tiotropium, a corticosteroid and a cromoglicic acid derivative
EP2528597B1 (en) Dry powder formulation comprising a pharmaceutical combination of tiotropium bromide, formoterol fumarate and mometasone furoate
EP2515845B1 (en) Dry powder combination of tiotropium, formoterol and a cromoglicic acid derivative
US8834931B2 (en) Dry powder formulation containing tiotropium for inhalation
WO2011078817A1 (en) Combination of tiotropium, mometasone and a cromoglicic acid derivative in dry powder form
EP2515846B1 (en) Dry powder combination of tiotropium, budesonide and a cromoglicic acid derivative
EP2804589A1 (en) Pharmaceutical formulations comprising aztreonam
WO2011037550A2 (en) Dry powder combination of tiotropium
WO2013109212A1 (en) Dry powder formulations comprising ciclesonide
WO2013109213A2 (en) Pharmaceutical formulations comprising tiotropium
WO2013109207A1 (en) Dry powder formulations comprising mometasone
WO2013109209A1 (en) Dry powder formulations comprising fluticasone

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: 10773176

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase in:

Ref country code: DE

REEP Request for entry into the european phase

Ref document number: 2010773176

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2010773176

Country of ref document: EP