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WO2001085243A1 - Chambre pour inhalateur - Google Patents

Chambre pour inhalateur Download PDF

Info

Publication number
WO2001085243A1
WO2001085243A1 PCT/GB2001/001993 GB0101993W WO0185243A1 WO 2001085243 A1 WO2001085243 A1 WO 2001085243A1 GB 0101993 W GB0101993 W GB 0101993W WO 0185243 A1 WO0185243 A1 WO 0185243A1
Authority
WO
WIPO (PCT)
Prior art keywords
chamber
chamber according
medicament
particulate material
charge
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
PCT/GB2001/001993
Other languages
English (en)
Inventor
Philip Braithwaite
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.)
Innovata Ltd
Innovata Biomed Ltd
Original Assignee
Innovata Biomed Ltd
ML Laboratories PLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB0010742A external-priority patent/GB0010742D0/en
Priority claimed from GB0011743A external-priority patent/GB0011743D0/en
Application filed by Innovata Biomed Ltd, ML Laboratories PLC filed Critical Innovata Biomed Ltd
Priority to AU62479/01A priority Critical patent/AU6247901A/en
Publication of WO2001085243A1 publication Critical patent/WO2001085243A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61M15/0086—Inhalation chambers
    • 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
    • A61M15/02—Inhalators with activated or ionised fluids, e.g. electrohydrodynamic [EHD] or electrostatic devices; Ozone-inhalators with radioactive tagged particles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
    • B05B5/025—Discharge apparatus, e.g. electrostatic spray guns
    • B05B5/057—Arrangements for discharging liquids or other fluent material without using a gun or nozzle
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
    • B05B5/16—Arrangements for supplying liquids or other fluent material
    • B05B5/1683—Arrangements for supplying liquids or other fluent material specially adapted for particulate materials

Definitions

  • This invention relates to a novel form of chamber and to inhalers used in conjunction with such a chamber.
  • a dry powder inhaler (DPI) will produce a cloud of solid medicament or medicament and excipient particles.
  • a metered dose inhaler MDI
  • a nebuliser will produce a mist comprising a solution or suspension of medicament particles in a solvent, usually water.
  • conventional inhalers act by delivery of an aerosol, whether that be particles dispersed in a propellant gas (MDI) or in air (DPI).
  • aerosol used hereinafter shall be taken to encompass any conventionally delivered medicament particles and shall not be restricted to MDIs.
  • the optimum particle size range is from 1 to 10 ⁇ m.
  • Achieving such an aerosol is dependant on a number of factors including the processing of the medicament and/or excipient particles (often by micronisation) and suitable formulation of the product.
  • the characteristics and performance of the delivery device are also critical in determining the extent of medicament delivery to the targeted pulmonary regions.
  • optimum delivery is itself influenced by a number of variables, including, but not limited to, the static interaction between medicament particles, between medicament particles and an excipient, and between medicament particles and the surfaces of the delivery device.
  • Medicament particles will tend to agglomerate to produce particles outside the optimum range of 1 to 10 ⁇ m.
  • Deagglomeration is usually attempted by the use of a carrier e.g. lactose.
  • a carrier e.g. lactose.
  • applying energy to a powder in order to deagglomerate it and create an aerosol of fine particles creates electrostatic charges on the particle surfaces.
  • These electrostatic charges cause particles to be attracted to corresponding oppositely charged particles and/or to charged (or neutral/earthed) surfaces.
  • the electrostatic charges can cause a reduction in optimisation of the delivery of medicament due to, inter alia, agglomeration or surface depositing of the medicament.
  • Particles can become charged (intentionally or not) in a variety of manners. The three most common methods are triboelectrification, corona charging and induction charging.
  • Triboelectric charging is the process of charging by frictional effects only and arises from two materials being rubbed together and then subsequently separated.
  • Corona charging uses an electrode with a sharp point, or consisting of a fine-gauge wire, is connected directly, or via a high voltage ballast resistance, to a high voltage source.
  • This type of electrode geometry causes significant field enhancement near the electrode, and for a high enough voltage, corona discharges are initiated, as the limiting value of the reduced electric field E/n (E is the electric field and n is the number density of the gas) is exceeded.
  • the polarity of the discharge may be either positive or negative. For a negative polarity the electrons, which have a high mobility, are rapidly trapped by air molecules to form a low-mobility negative ion.
  • the method of induction charging is widely used in liquid charging systems and requires the particle that is to be charged to be more conductive (p ⁇ 10 8 ⁇ m) than most powder particles.
  • electronic conduction through the bulk of the material may be achieved relatively easily, and it will readily acquire charge of the same polarity as the electrode and will retain this charge when contact is broken. Since no free ions are produced, the system performance will be similar to that of a tribo-charged system.
  • Drug delivery to the bronchial system can be administered either orally or directly.
  • Oral administration has an efficiency of about 0.5% ' whereas direct administration is about 10% efficient, and is thus the method of choice.
  • the particle size should be in the range 2-5 ⁇ m. Above 5 ⁇ m impaction limits the progress of particles. This occurs primarily at the bifurcation of airway surfaces.
  • fine particles of a carrier e.g. lactose
  • a carrier e.g. lactose
  • lactose particles were in the range 63-90 ⁇ m and those of the fine particles were ⁇ 10 ⁇ m. It was found that the triboelectric charge acquired by passing the powders through a stainless steel pipe, had a negative polarity, and ranged from about 70 nC g "1 for a powder with no fine particles to about 8 nC g " for a powder with 30% fine particles.
  • a further alternative device is that described by K ⁇ hler in European Patent Application No 95118325.0.
  • antistatic spacers are known, for example, a device comprising a metal spacer is available from Astra Zeneca
  • the device of the invention utilises an inherent/existing charge in particulate material and/or applies a charge . to such particles, by exciting and energising the particles.
  • a charge to the chamber and/or the particulate material, movement is generated in the particles by charge repulsion/attraction; and a "floating cloud" of particulate material can be produced which prevents deposition and/or agglomeration of particles.
  • a chamber for use in the delivery of a particulate material which comprises means for introducing an electric charge to the chamber and/or the particulate material and means for separating coarse particles from fine particles.
  • the electric charge is applied to the particulate material, such a charge may be applied directly to the particles or may be applied via the charge applied to the chamber. Furthermore, charge may be applied solely to the particles or the charge may be applied to both the particles and the chamber.
  • the charge is applied solely to the chamber.
  • charge can be applied to both the chamber and the particulate material.
  • the means for introducing an electric charge to the chamber will comprise at least a pair of electrodes.
  • the means will comprise a plurality of such pairs of electrodes, generally greater control and usability is achieved if the number of electrodes is increased.
  • the electrodes are used to set up a substantially uniform field of charge within the space of the chamber.
  • the performance of the chamber may be optimised by varying, for example, the configuration of the chamber, the applied voltage, the electrode gap spacing, the peak and/or average electric field, the atmospheric conditions, particulate composition and size, the pulse width, the number of electrodes and/or the repetition rate.
  • the output of the pairs of electrodes may vary from between 1 v and 50 kN, more preferably between 1 v and 10 kV, most preferably between 1 kN and 10 kV, for example 5 kN to 10 kV and especially 7 or 8 kN.
  • the means for separating the fine and coarse particles will generally comprise at least a pair of electrodes.
  • the means comprises a plurality of pairs of electrodes connected such that the power to each of the electrodes will be pulsed.
  • the separation of coarse and fine particles may occur separately, simultaneously or sequentially with the application of the electric charge.
  • the separation may occur separately to the application of electric charge. Alternatively it may occur simultaneously.
  • the separation occurs sequentially with application of the electric charge.
  • the charge to mass ratio is higher for smaller particles, the fine particles will be repelled away from the electrodes, e.g. to the middle portion of the chamber, whilst the coarser particles will remain closer to the electrodes, e.g. inner surface of the chamber.
  • the frequency of the pulsed power may be varied, depending, inter alia, upon the size and nature of the medicament particles being delivered.
  • a frequency of between 0.1 and 1000 pulses per second (pps) is desirable, preferably a frequency between 100 and 1000 pps is desirable, more preferably between 200 and 800 pps.
  • the chamber of the invention is especially advantageous in the delivery of medicaments and especially particulate material in the form of a powder.
  • powdered medicaments are especially useful as an inhalation therapy e.g. in the treatment of respiratory disorders or systemic disorders, for example, insulin dependent diabetes.
  • an inhaler system comprising an inhaler in conjunction with a chamber as hereinbefore described.
  • the inhaler and chamber of the invention may be provided separately, together or as a kit of parts.
  • the particle size of the medicament may be varied depending, inter alia, on the type of aerosol being formed.
  • the particle size of the medicament, and the carrier, if one is present may be varied.
  • the nature of the carrier may also be varied.
  • the particle size of the medicament may be substantially between 1 and 20 ⁇ m, more preferably between 1 and 10 ⁇ m. That is, at least 90% w/w of the medicament should have a particle size of between 1 and 20 ⁇ m.
  • a variety of carriers may be used. Certain carriers may be mentioned, by way of example only, such as sugars, e.g. dextran, mannitol and lactose, for example cc-lactose monohydrate.
  • the particle size of the carrier may be across a wide range, between 0.1 and 500 ⁇ m, preferably between 1 and 200 ⁇ m, more preferably between 1 and 100 ⁇ m and especially between 1 and 20 ⁇ m.
  • he carrier may itself comprise a mixture of fine and coarse particles.
  • the chamber may be substantially spherical in shape.
  • a plurality of electrodes may be situated around the periphery of the chamber.
  • the chamber may comprise a plurality of segments wherein each segment comprises an electrically conductive portion and an electrically insulating portion.
  • each segment may comprise an electrically conducting inner portion with an electrically insulating outer portion.
  • the inner portion preferably comprises a mesh arrangement and especially an electrically conducting wire mesh.
  • the outer portion can comprise any conventionally known insulating material, such as a plastics material.
  • each segment is preferably a parabolic shape to facilitate coupling a plurality of such segments to form a sphere.
  • Each of the parabolic shaped segments may be connected to a pulsed and phased high voltage generator.
  • the generator has three phase connections A, B and C and are connected to the parabolic segments in sequence as follows: A connected to 1, 4, 7 and 10, B connected to 2, 5, 8 and 11 and C connected to 3, 6, 9 and 12.
  • the inhaler system of the invention is therefore useful in the treatment of e.g. bronchial disorders. Therefore, any medicaments and/or excipients known to be used in such treatments may be used in the inhaler system of the invention.
  • a variety of medicaments may be administered by using the inhaler system of the invention.
  • Such medicaments are generally antibiotics, bronchodilators or other anti-asthma drugs.
  • Such medicaments include, but are not limited to bronchodilators, e.g. fenoterol, formoterol, pirbuterol, reproterol, rimiterol, salbutamol, salmeterol and terbutaline; non-selective beta-stimulants such as isoprenaline; xanthine bronchodilators, e.g. theophylline, aminophylline and choline theophyllinate; anticholinergics, e.g. ipratropium bromide; mast cell stabilisers, e.g. sodium cromoglycate and ketotifen; bronchial anti-inflammatory agents, e.g. nedocromil sodium; and steroids, e.g. beclomethasone dipropionate, fluticasone, budesonide and flunisolide; and combinations thereof.
  • bronchodilators e.g. fenoterol, formoterol, pirbut
  • Specific combinations of medicaments which may be mentioned include combinations of steroids, such as, beclomethasone dipropionate, fluticasone, budesonide and flunisolide; and combinations of to bronchodilators, such as, formoterol and salmeterol. It is also within the scope of this invention to include combinations of one or more of the aforementioned steroids with one or more of the aforementioned bronchodilator. A specific combination which is preferred is a combination of fluticasone and salmeterol.
  • medicaments which may be mentioned include systemically active materials, such as, proteinaceous compounds and/or macromolecules, for example, hormones and mediators, such as insulin, human growth hormone, leuprolide and alpha interferon; growth factors, anticoagulants, immunomodulators, cytokines and nucleic acids.
  • hormones and mediators such as insulin, human growth hormone, leuprolide and alpha interferon
  • growth factors such as growth factors, anticoagulants, immunomodulators, cytokines and nucleic acids.
  • a further feature of the invention we provide a method of admimstering a medicament to a patient using an inhaler system as hereinbefore described.
  • a method of treatment of a patient suffering from a disorder which comprises the administration of a therapeutically effective amount of an appropriate medicament using an inhaler system as hereinbefore described.
  • the methods of the invention comprise: (i) introducing the medicament into the chamber;
  • any conventional l ⁇ iown power source may be used in conjunction with the device of the invention.
  • the power source may be battery driven or mains supply driven.
  • a dc source may be from 1 to 100 v and ' an ac source from 1 to 240 v
  • Figure 1 is a perspective view of a parabola shaped segment
  • Figure 2 is a perspective view of a chamber
  • Figure 3 is an end view of a chamber
  • Figure 4 is an end view of the chamber showing the circuitry arrangement
  • Figure 5 is an end view of the chamber showing the particle distribution within the chamber.
  • a chamber segment (1) comprises a parabolic shaped wire mesh (2) held in a plastics frame (3).
  • Each end (4 and 5) of the frame (3) is provided with a lug (6 and 7) which enables a plurality of segments (1) to be held together.
  • a plurality of parabolic segments (1) are placed together to make a sphere (8).
  • the lugs (6 and 7) lie adjacent to each other in a circular arrangement (not shown) and a fixing ring (9 and 10) is slotted over each end (11 and 12) holding the lugs (6 and 7) together and retaining the spherical shape.
  • the first fixing ring (9) is apertured (not shown) also acts as an inlet and the second fixing ring (10) is apertured (13) to act as an outlet.
  • an electrical circuit is connected to the wire mesh (2) of the segments (1). All of the parabola shaped pieces are connected to a pulsed and phased high voltage generator.
  • the generator has three phase connections A, B and C and are connected to the parabola pieces in sequence as follows: A connected to 1, 4, 7 and 10, B connected to 2, 5, 8 and 11 and C connected to 3, 6, 9 and 12.
  • the plastics frames (3) act as an insulator for each segment (1).
  • a medicament or medicament and excipient formulation is introduced into the inside of the chamber from an inhaler through the inlet orifice (4).
  • the pulse generator is actuated, causing the particles to be charged. Those that are negatively charged are attracted to the positively charged portions of the sphere; and those that are positively charged to are attracted to the negatively charged portions of the sphere.
  • the pulses are phased, the particles are rapidly, alternatively attracted and repelled, forcing them into a rotating motion within the sphere.
  • An experimental electrospacer was instructed enabling a series of experiments to be undertaken with different types of powders. This device was flexible and versatile to enable a number of different geometries to be tested. It was also large enough to allow suitable diagnostic techniques to be incorporated. A fixed high voltage framework was developed that allows different electrode configurations to be examined. A suitable pulse generator was also developed to drive the experimental electrospacer.
  • the experimental electrospacer was used to characterise the behaviour of different ⁇ powders within the electric field.
  • electrical parameters that influence particle motion including electric field intensity, voltage pulse duration and pulse repetition frequency, electrode geometry and phase requirements.
  • Each powder type requires its own set of parameter values for initial capture and stable confinement.
  • the important powder properties that were examined during this experimental stage include density, appearance (fluffy or pellet), conductivity (water content), electrical permitivity and mass/size.
  • Example 3 The results from Example 3 were considered to identify specifications for a prototype electrospacer and suitable pulse generator.
  • the design was specific to one type of powder.
  • the prototype design takes into account operational issues such as size, power requirements and safety.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention se rapporte à une chambre qui est conçue pour l'administration d'une matière particulaire et comporte un moyen permettant d'y introduire une charge électrique et/ou la matière particulaire, ainsi qu'un moyen permettant de séparer les grosses particules des particules fines. L'invention se rapporte également à un système inhalateur comportant une telle chambre et à un procédé d'administration d'un médicament à un patient au moyen d'un tel système inhalateur.
PCT/GB2001/001993 2000-05-05 2001-05-04 Chambre pour inhalateur Ceased WO2001085243A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU62479/01A AU6247901A (en) 2000-05-05 2001-05-04 Inhalation chamber

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0010742.5 2000-05-05
GB0010742A GB0010742D0 (en) 2000-05-05 2000-05-05 Chamber
GB0011743A GB0011743D0 (en) 2000-05-17 2000-05-17 Chamber
GB0011743.2 2000-05-17

Publications (1)

Publication Number Publication Date
WO2001085243A1 true WO2001085243A1 (fr) 2001-11-15

Family

ID=26244212

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2001/001993 Ceased WO2001085243A1 (fr) 2000-05-05 2001-05-04 Chambre pour inhalateur

Country Status (2)

Country Link
AU (1) AU6247901A (fr)
WO (1) WO2001085243A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2781232A1 (fr) * 2013-03-21 2014-09-24 Ca-Mi S.R.L. Dispositif pour faciliter l'inhalation de produits médicinaux
EP3645092B1 (fr) * 2017-06-30 2024-04-03 Avectas Limited Cathéter d'électronébulisation

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993000951A1 (fr) 1991-07-02 1993-01-21 Inhale, Inc. Procede et dispositf d'administration de medicaments en aerosol
WO1994019042A1 (fr) * 1993-02-19 1994-09-01 Bespak Plc Appareil pour inhalation
WO1996010459A2 (fr) * 1994-10-04 1996-04-11 Imperial Chemical Industries Plc Pulverisation electrostatique de matiere particulaire
WO1996040441A1 (fr) * 1995-06-07 1996-12-19 Imperial Chemical Industries Plc Pulverisation electrostatique
US5875776A (en) * 1996-04-09 1999-03-02 Vivorx Pharmaceuticals, Inc. Dry powder inhaler

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993000951A1 (fr) 1991-07-02 1993-01-21 Inhale, Inc. Procede et dispositf d'administration de medicaments en aerosol
WO1994019042A1 (fr) * 1993-02-19 1994-09-01 Bespak Plc Appareil pour inhalation
WO1996010459A2 (fr) * 1994-10-04 1996-04-11 Imperial Chemical Industries Plc Pulverisation electrostatique de matiere particulaire
WO1996040441A1 (fr) * 1995-06-07 1996-12-19 Imperial Chemical Industries Plc Pulverisation electrostatique
US5875776A (en) * 1996-04-09 1999-03-02 Vivorx Pharmaceuticals, Inc. Dry powder inhaler

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2781232A1 (fr) * 2013-03-21 2014-09-24 Ca-Mi S.R.L. Dispositif pour faciliter l'inhalation de produits médicinaux
EP3645092B1 (fr) * 2017-06-30 2024-04-03 Avectas Limited Cathéter d'électronébulisation

Also Published As

Publication number Publication date
AU6247901A (en) 2001-11-20

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