[go: up one dir, main page]

WO2002007705A1 - Materiau support pour inhalation de poudre seche - Google Patents

Materiau support pour inhalation de poudre seche Download PDF

Info

Publication number
WO2002007705A1
WO2002007705A1 PCT/EP2001/008395 EP0108395W WO0207705A1 WO 2002007705 A1 WO2002007705 A1 WO 2002007705A1 EP 0108395 W EP0108395 W EP 0108395W WO 0207705 A1 WO0207705 A1 WO 0207705A1
Authority
WO
WIPO (PCT)
Prior art keywords
carrier
dry powder
powder inhalation
carrier material
produced
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/EP2001/008395
Other languages
English (en)
Inventor
Klass Daniel Kussendrager
Mark Jason Heath Ellison
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.)
Campina Melkune BV
Original Assignee
Campina Melkune BV
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 Campina Melkune BV filed Critical Campina Melkune BV
Priority to AU2001279771A priority Critical patent/AU2001279771A1/en
Publication of WO2002007705A1 publication Critical patent/WO2002007705A1/fr
Anticipated expiration legal-status Critical
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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system

Definitions

  • the present invention relates to a carrier material for use in dry powder inhalation formulations, to the process for manufacture of these carrier materials and to dry powder inhalation formulations using the carrier materials.
  • Dry powder inhalers have been in existence since the late 1960 's. Interest in this technique for delivering pharmacological active components to the lungs was initially limited due to the popularity of pressurized metered dose inhalers (pMDI's). However, since the decision to eliminate CFC's from pMDI's due to environmental issues, dry powder inhalers are becoming more popular.
  • pMDI's pressurized metered dose inhalers
  • formulations for dry powder inhalation comprise a pharmacologically active component and an inert carrier material, being in most cases ⁇ -lactose monohydrate crystals.
  • the active component is usually micronised with a particle size less than 5 ⁇ m, to enable deposition in the lower levels of the lungs.
  • the purpose of the inert carrier is to aid flow and to prevent the formation of agglomerates of the active component which agglomerates can not be dispersed, thus preventing deposition at the site of action.
  • ⁇ -lactose does not have an optimal flow, which may lead to problems, such as clogging, in the inhaler.
  • ⁇ -lactose monohydrate does not always lead to a 100% drug delivery.
  • the carrier hits the throat, after which the drug, which is in loose association with the carrier, detaches therefrom and is transported to the lungs where it has its effect. In case the drug does not end up in the right location, i.e. the lung, there may arise problems for the patient.
  • spray-dried carrier material consists of spherical particles, which show excellent flow characteristics, but that spray dried products may contain amorphous material which can undergo crystallisation in the presence of moisture.
  • the active ingredient such as a drug
  • a crystallisation step should be incorporated into the manufacture of the carrier material .
  • the purpose of the crystallisation step is to remove substantially all, and preferably all the amorphous material present.
  • the present invention thus relates to a carrier material, comprising carrier particles that are spherical in nature and contain substantially no or no amorphous material.
  • carrier material is for example obtainable by a method comprising the steps of: a) providing a carrier base material consisting of spherical carrier particles; and b) crystallising the carrier base material in order to remove amorphous material present in the particles to obtain the carrier material.
  • the provision of the spherical carrier base material can be achieved by spray drying a starting material to obtain a powder that consists of substantially spherical particles of the carrier material that still contain amorphous material.
  • a suitable method for obtaining such carrier base material is described in EP-239 172, which is incorporated herein by reference.
  • the method described therein comprises feeding a slurry of crystalline ⁇ -lactose hydrate in a saturated lactose solution to a spray drier and drying the same, wherein the selection of the ratio between the amounts of crystalline material and dissolved lactose in the slurry determines the ratio between the amounts of crystalline and amorphous lactose in the spray dried product.
  • the person skilled in the art of spray drying can modify the process conditions to obtain a suitable spray dried product based on his common general knowledge of spray drying.
  • the present invention thus provides a spray dried product with substantially no or no amorphous material, by virtue of which it has excellent flow properties and is stable with regard to air moisture.
  • Preferred carrier materials are those known to be useful for dry powder inhalation formulations.
  • monosaccharides such as glucose, fructose, mannose etc. and the polyols derived therefrom like sorbitol, mannitol etc.
  • disaccharides such as lactose, maltose, sucrose and their derivatives such as lactitol, maltitol, and oligo- and polysaccharides such as dextrins and starches.
  • the carrier base material for the spray drying process can be one of the above mentioned materials or combinations of these.
  • the carrier base material is a crystalline carrier base material, in particular a crystalline sugar such as glucose, fructose, sucrose or mannitol and most preferably the carrier base material is lactose.
  • the amorphous content of the spray dried product (base powder) is generally within the range 0.5% to 50%.
  • the amorphous material present in the spray dried powder particles can then be crystallised by any suitable method.
  • a particularly preferred method yielding good results is the use of a fluid bed dryer using suitable conditions with regard to temperature and relative humidity which allow the amorphous material to crystallise.
  • Suitable temperature conditions are a temperature of 20 to 100°C, preferably 30 to 90°C, more preferably 40 to 80 °C, even more preferably 50 to 70 °C, most preferably 60°C in combination with a suitable relative humidity of 80% to 10%, preferably 70 to 15%, more preferably 60 to 20%, even more preferably 50 to 25%, further more preferably 40 to 30%, most preferably 35%.
  • the carrier material of the invention produced for the purpose of dry powder inhalation has a particle size typically between 1 ⁇ m and 400 ⁇ m. Preferably, the particle size is between 40 ⁇ m and 300 ⁇ m. Typically, at least 90% of the particles are within this latter range.
  • the present invention furthermore relates to a dry powder inhalation formulation which contains a carrier material of the invention and at least one pharmacologically active component.
  • the active component may be selected from the group consisting of steroids, sympathomimetics, mucolytics, proteins, peptides, sodium cromoglycate or from the group consisting of hypnotics, sedatives, analgesics, ani-inflammatory agents, anti-histamines, anticonvulscents, muscle relaxants, anti-spasmodics, anti-bacterials, antibiotics, cardiovascular agents and hypoglycaemic agents.
  • the active component is budesonide or alternatively sodium cromoglycate.
  • ⁇ -lactose monohydrate is commonly used in dry powder inhalation formulations. It has generally a good performance, but over time the problems described in the specification, i.e. crystallisation upon contact with air humidity and thus decreased stability and performance, may occur.
  • ⁇ -lactose monohydrate standard crystal form of lactose
  • non-pretreated ⁇ -lactose monohydrate and a selected size fraction of the carrier material of the invention were used in an inhalation formulation.
  • a second control standard spray dried lactose was used as a second control standard spray dried lactose was used.
  • a suspension of a fine milled ⁇ -lactose monohydrate powder in an aqueous lactose solution was spray dried, resulting in a spray dried powder with approximately 20% amorphous lactose. This represents the standard spray dried lactose.
  • the amorphous lactose in the spray dried powder obtained above was then crystallised by a treatment in a fluid bed dryer at a temperature of 60 °C and a relative humidity of 35 % to obtain a powder having 90% of the particles in the particle size range from 40- 300 ⁇ m.
  • ⁇ -Lactose monohydrate was obtained from DMV International, Veghel, the Netherlands.
  • Budesonide was used as the active component, with an active ingredient to carrier ratio of 1:62.5.
  • the formulations were prepared using a tumble mixer.
  • the budesonide concentrations were determined by UV spectroscopy.
  • the performance of the formulations was assessed in vitro using the multi-stage liquid i pinger, with the method described in the USP24.
  • the device used was a multidose inhaler, utilising a reservoir system. The results obtained are shown in table 1 as a percentage (%) of the nominal dose.
  • the fraction "Stage 3 + 4 + filter" is considered as the fraction reaching the lungs

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Otolaryngology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un matériau support destiné à des formulations d'inhalation de poudre sèche, constitué de particules support sphériques en nature et ne contenant pas de matériau amorphe. Elle concerne, en outre, un procédé de préparation d'un matériau support destiné à des formulations d'inhalation de poudre sèche, consistant à disposer d'un matériau support de base constitué de particules support sphériques et à cristalliser le matériau support de base de façon à éliminer les parties amorphes présentes dans les particules afin d'obtenir le matériau support.
PCT/EP2001/008395 2000-07-20 2001-07-19 Materiau support pour inhalation de poudre seche Ceased WO2002007705A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001279771A AU2001279771A1 (en) 2000-07-20 2001-07-19 Carrier material for dry powder inhalation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NL1015751 2000-07-20
NL1015751 2000-07-20

Publications (1)

Publication Number Publication Date
WO2002007705A1 true WO2002007705A1 (fr) 2002-01-31

Family

ID=19771766

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2001/008395 Ceased WO2002007705A1 (fr) 2000-07-20 2001-07-19 Materiau support pour inhalation de poudre seche

Country Status (2)

Country Link
AU (1) AU2001279771A1 (fr)
WO (1) WO2002007705A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003082253A1 (fr) * 2002-03-28 2003-10-09 Lab Pharma Oy Procede de traitement de particules de support et utilisation correspondante
WO2003070908A3 (fr) * 2002-02-19 2004-10-28 Dow Agrosciences Llc Nouvelles polyketide synthases produisant des spinosynes
WO2006037738A1 (fr) * 2004-10-01 2006-04-13 Boehringer Ingelheim International Gmbh Modification de surfaces de lactose utilise comme auxiliaire, pour des agents d'inhalation pulverulents
WO2006037736A1 (fr) * 2004-10-01 2006-04-13 Boehringer Ingelheim International Gmbh Poudres a inhaler a base de melanges de lactoses modifies comme auxiliaires
WO2008058691A3 (fr) * 2006-11-15 2008-10-23 Jagotec Ag Améliorations se rapportant à des composés organiques
US8414867B2 (en) 2003-11-14 2013-04-09 Jagotec Ag Dry powder formulations
US8877251B2 (en) 2005-12-12 2014-11-04 Jagotec Ag Powder compositions for inhalation
CN111643487A (zh) * 2020-06-12 2020-09-11 苏州大学 一种乳糖微球及其制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0239172A2 (fr) * 1986-03-21 1987-09-30 Dmv-Campina B.V. Lactose séché par pulvérisation de qualité améliorée et son procédé de préparation
US5254330A (en) * 1990-01-24 1993-10-19 British Technology Group Ltd. Aerosol carriers
US5376386A (en) * 1990-01-24 1994-12-27 British Technology Group Limited Aerosol carriers
WO1998031346A1 (fr) * 1997-01-16 1998-07-23 Massachusetts Institute Of Technology Preparation de particules pour inhalation
US5874063A (en) * 1991-04-11 1999-02-23 Astra Aktiebolag Pharmaceutical formulation

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0239172A2 (fr) * 1986-03-21 1987-09-30 Dmv-Campina B.V. Lactose séché par pulvérisation de qualité améliorée et son procédé de préparation
US5254330A (en) * 1990-01-24 1993-10-19 British Technology Group Ltd. Aerosol carriers
US5376386A (en) * 1990-01-24 1994-12-27 British Technology Group Limited Aerosol carriers
US5874063A (en) * 1991-04-11 1999-02-23 Astra Aktiebolag Pharmaceutical formulation
WO1998031346A1 (fr) * 1997-01-16 1998-07-23 Massachusetts Institute Of Technology Preparation de particules pour inhalation

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003070908A3 (fr) * 2002-02-19 2004-10-28 Dow Agrosciences Llc Nouvelles polyketide synthases produisant des spinosynes
WO2003082253A1 (fr) * 2002-03-28 2003-10-09 Lab Pharma Oy Procede de traitement de particules de support et utilisation correspondante
US8414867B2 (en) 2003-11-14 2013-04-09 Jagotec Ag Dry powder formulations
US7736628B2 (en) 2004-10-01 2010-06-15 Boehringer Ingelheim International Gmbh Powdered inhalants based on modified lactose mixtures as excipient
JP2008514675A (ja) * 2004-10-01 2008-05-08 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 粉末吸入剤のために使用される助剤として機能するラクトースの表面の改質
JP2008514674A (ja) * 2004-10-01 2008-05-08 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング アジュバントとして使用される改質ラクトースブレンドをベースとする新規粉末吸入製剤
US7658949B2 (en) 2004-10-01 2010-02-09 Boehringer Ingelheim International Gmbh Surface modification of lactose excipient for use in powders for inhalation
WO2006037736A1 (fr) * 2004-10-01 2006-04-13 Boehringer Ingelheim International Gmbh Poudres a inhaler a base de melanges de lactoses modifies comme auxiliaires
WO2006037738A1 (fr) * 2004-10-01 2006-04-13 Boehringer Ingelheim International Gmbh Modification de surfaces de lactose utilise comme auxiliaire, pour des agents d'inhalation pulverulents
US8877251B2 (en) 2005-12-12 2014-11-04 Jagotec Ag Powder compositions for inhalation
WO2008058691A3 (fr) * 2006-11-15 2008-10-23 Jagotec Ag Améliorations se rapportant à des composés organiques
JP2010509384A (ja) * 2006-11-15 2010-03-25 ヤゴテック アーゲー 有機化合物の、または有機化合物に関連する改良
AU2007321385B2 (en) * 2006-11-15 2013-08-22 Jagotec Ag Powder formulation for inhalation
CN111643487A (zh) * 2020-06-12 2020-09-11 苏州大学 一种乳糖微球及其制备方法

Also Published As

Publication number Publication date
AU2001279771A1 (en) 2002-02-05

Similar Documents

Publication Publication Date Title
EP0464171B1 (fr) Supports d'aerosols
US5376386A (en) Aerosol carriers
DE60025019T2 (de) Trockenpulverzusammensetzungen mit verbesserter dispersivität
CA2218116A1 (fr) Administration par voie pulmonaire de medicaments en aerosols
US20100092453A1 (en) Method of producing porous microparticles
HU217975B (hu) Polipeptidet higítóként melezitózt tartalmazó inhalációs porkészítmények és eljárás előállításukra
JP2003513031A5 (fr)
WO2005092301A1 (fr) Micro-particules a base d'insuline et hautement inhalables
WO2009050726A2 (fr) Compositions et procédé pour une délivrance améliorée de bupropione
JP2003533472A (ja) 吸入用インスリン製剤
EP1339388A1 (fr) Support d'inhalation particulaire
WO2002007705A1 (fr) Materiau support pour inhalation de poudre seche
CA2287333C (fr) Excipient pour inhalateur a poudre seche, son procede de preparation, et compositions pharmaceutiques le contenant
WO2007060384A2 (fr) Poudres respirables
PL207752B1 (pl) Sposób otrzymywania trwałego fizycznie i jednorodnego sproszkowanego preparatu zawierającego tiotropium, sproszkowany preparat i jego zastosowanie
US20050201948A1 (en) Excipient for use in dry powder inhalation preparations
JP2516542B2 (ja) 乳酸菌含有瀉下薬組成物
WO2003094884A1 (fr) Supports d'inhalation particulaire derives
Auriemma et al. Gentamicin and particle engineering: from an old molecule to innovative drug delivery systems
KR20200011133A (ko) 보센탄을 함유한 약학 제제
IE20070049A1 (en) A method of producing porous microparticles
KR20180052566A (ko) 폐 전달용 트립탄 분말

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP