WO1994014490A1 - Compacted drug body for use in the mechanical generation of inhalable active-substance particles - Google Patents

Compacted drug body for use in the mechanical generation of inhalable active-substance particles Download PDF

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Publication number
WO1994014490A1
WO1994014490A1 PCT/EP1993/001158 EP9301158W WO9414490A1 WO 1994014490 A1 WO1994014490 A1 WO 1994014490A1 EP 9301158 W EP9301158 W EP 9301158W WO 9414490 A1 WO9414490 A1 WO 9414490A1
Authority
WO
WIPO (PCT)
Prior art keywords
characterized
group
drug
drug supply
solid structure
Prior art date
Application number
PCT/EP1993/001158
Other languages
German (de)
French (fr)
Inventor
Bernhard Hugemann
Hans G. Burgschat
Helmut Heide
Joachim Pabst
Original Assignee
Bernhard Hugemann
Burgschat Hans G
Helmut Heide
Joachim Pabst
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 to DE4243649 priority Critical
Priority to DEP4243649.4 priority
Application filed by Bernhard Hugemann, Burgschat Hans G, Helmut Heide, Joachim Pabst filed Critical Bernhard Hugemann
Publication of WO1994014490A1 publication Critical patent/WO1994014490A1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M15/00Inhalators
    • A61M15/0065Inhalators with dosage or measuring devices
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/06Solids
    • A61M2202/062Desiccants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/06Solids
    • A61M2202/064Powder
    • A61M2202/066Powder made from a compacted product by abrading

Abstract

The invention concerns a compacted drug body with an isotropic solid structure, the compacted body being produced by isostatic compression.

Description

description

Solidified drug supply for the mechanical production of inhalable particles of active substance

The invention relates to a solidified Arzneistoff¬ supply in the form of a solid, are processed by the means of mechanical tools such as a face mill, the active ingredient particles and sucked by inhalation into the respiratory tract.

From the European patent application 0407 028 A 2, an inhaler is known in which the medicament is arranged as a so--called "compacted body" in the inhaler. By "compacted body" a drug is hereby ver¬ were, which is pressed out of loose powder so largely zusammenge¬ that the active ingredient particles sammenhalten zu¬ to abrasion. As compaction pressures are ge in the application Nannt 1 x 104 to 15 x 104 Nm-2 and 30 x 10 to 15Öx 10 4 Nm-2 # B e i such pressures the powder compact is highly porous and permeable to gas in spite of the compaction. The reference in the notification that the "compacted body" is set at relatively low pressure of micronized drug her¬, means that the active compound to be processed particles retain a micronized structure. Such fine powders is now known physico-chemically highly active phase states is that companies have with regard to the inhalation application the following negative Eigen¬:

- Micronized powders tend almost instantly to agglomerate and form larger particles networks that are not inhalable or Dosierein¬ directions not at first in a reproducible manner can ver¬.

- Micronized powder can in storage and

ADJUSTED SHEET (RULE 91) segregate during transport. This refers in particular powder mixture of different substances. - Due to the very large specific surface are micronized powders chemically very active and nei¬ gene to storage instability (water uptake, oxidation and the like.)

Because of these properties are Inhalatorsysteme that are based on the use of loose or slightly ko paktierter micronized starting materials, in its capacity dosing, drug safety, Be¬ dienungsweise and long term stability hin¬ clearly unsatisfactory.

DE-OS 40 27 390, an inhaler is known in which the medicinal substance is present in form of solidified Tabletten¬ and the active ingredient particles are processed by means of a brush. Of technical data on the consolidation is merely mentioned that the Aus¬ input variable for the compacted powder <^ 1 OA "* - is. This means that it is also here to micronized powder with the above mentioned disadvantages.

The object of the invention is a solidified Arzneistoff¬ stock for the mechanical generating inhalable active compound particles, which avoids the mentioned disadvantages.

According to the invention it is proposed that the stock material Arznei¬ an isotropic solid structure has. By this is meant that the bonding strength of grain is located in a monolithic solid to grain in the same order of magnitude as the specific Eigen¬ strength of the structure-forming constituents. Here, the strength, density and composition of the solid is homogenous.

The solid and homogeneous structure of the invention of Arznei¬ material is depleted allows a defined and particulate material quantities reproducible in dosage processing of Wirk¬. Loosely integrated Partikelver¬ frets and agglomerates can not occur.

The solidified drug, stock can be made in any form. Preferably, this is formed as dick¬ walled annular body. This geometric Ge staltung of the drug supply has the following advantages:

The internal cavity of the ring can be used as the start of the Inha¬ lationsrohres so that the Wirkstoffpar¬ tion may occur in the pipe Inhala¬ Tikel immediately after their generation. Dead flow zones are avoided. In a ring, the wall thickness can be selected so that the differences of the speeds of the Geschwindig¬ processing element at the inner and outer ring diameter with respect to the total area to vernach¬ are permeable. As is known, the speed in the center of a solid body would be zero. This would to a defined Un¬ removal from the active compound body and thus lead Un¬ defined particle generation.

The drug inventive material supply can be made that inhale as aerosols and can be used to treat certain diseases of pure drugs alone or drug-excipient combinations there are suitable.

Taking advantage of the new Arznei¬ material preparation according to the invention, the treatment options are er¬ considerably expanded. In addition to the now well-known and established therapies of Atemwegser¬ diseases such as asthma, are inhalable by the erfindungs¬ modern pharmaceutical preparation not only the established drugs but also other, not yet through the respiratory tract appl iz ierbare agents. These are in particular:

Respiratory medicines for example from the group of betamimetics: fenoterol,

Salbutamol, Salmetarol, terbutaline, among others as well as their pharmakologi see active enantio ere from the group of Antichol inergika: Ipratopium- bromide, inter alia from the group of steroids: Budesonide, R-budesonide, Beclamtason, fluticasone, inter alia from the group of anti al lergi ka: Dinatriumchromog LY cat, ketotifen, inter alia from the group of most PAF Antagoni: Gingkolide,

WEB-2086 inter alia Other respiratory drugs such as amiloride, furosemide id, Kai ium channel -Akti vatoren, inhibitors leukotriene In¬ and Bradi kinin-Antagoni most peptide hormones

Insulin, calcitonin, desmopressin, inter alia, drugs for controlling addiction, nicotine, methadone, levo ethadon inter alia Narkoanalgetica / Neuroleptanalgetica buprenorphine, dehydrocodeine, fentanyl, inter alia, for example, alkaloids Scopol amine, inter alia, chemotherapeutic agents such as pentamidine inter alia

These agents may be mixed materials alone or in a homogeneous distribution with effective neutral Zusatz¬ in powder form that are suitable for a Inhalationsap¬ plication. By using these additives following functions can be predetermined - dilution of highly effective drugs

- adjustment of the specific mechanical properties of the active ingredient Abtragungs¬ body relative to the Ab¬ tragungselement of the inhaler

- excipients for adjusting the Verarbeitungseigen¬ properties of the active agent / carrier combination to the manufacturing technique.

As an effective neutral excipients such as lactose, glucose, mannitol, sodium chloride and mixtures of these currently eligible, the arbeitungs- is to adjust certain supply and abrasion properties have proved and for diluting the active ingredients in the abrasive particles to be advantageous.

According to the invention solidified drug stocks with an isotropic solid structure of pourable pharmaceutical preparations, preferably granules, manufactured by isostatic pressing at pressures between 50 and 500 megapascals. Isostatic pressing, the all-round uniform pressure transmission is understood in the bulk material. For this purpose correspondingly shaped elastic matrices are used, for example, which are deformed by hydraulic pressure to the desired Kör¬ per. This gives rise to a homogeneous, uniformly thick and loose texture structure which meets the requirements of drug reserves in inhalers in an optimum manner.

In a further development of the invention, fabric molding stocks pl is astifiz FOURTH Mas.sen, melting method, die casting and the like used in the preparation of isotropic solidified medicine.

The resistance of the Zubereitungs¬ inventive shape to chemical aging, Feuchtigkeitsauf¬ takeover and other changes (shelf life) is another advantageous property. By reducing the active surface due to the he find proper Ko of the starting materials paktierung is a considerable improvement in the storage stability ranges er¬.

In the drawings the invention is described in more detail:

Fig. 1 shows, in section according to the invention Verpackungs¬ unit of the drug supply,

Fig. 2 is a Originalmeßkurve the Partikelver¬ shows distribution of the non mi KRONI overbased starting powder for producing a tablet according to the invention Ring¬,

Fig. 3 shows a corresponding measurement curve of the generated microparticles of an inventively hergestell th ring tablet of this powder (Figure 2).

Particularly in the case of sensitive active ingredients, such to Example strongly hygroscopic substances not¬ agile storage stability by a corresponding Ver¬ packaging the drug supply 2 (Fig. 1) are supported. The drug substance of the invention stock 2 is inserted into an inhalation tube 1 and, together with the material body In¬ halationsrohr replaced when replacing the spent Wirk¬. The drug supply and the inhalation tube are housed together in a container, which also serves as a closure cap for the inhaler.

In the upper part of the cap 5 there is an air-permeable container 6 in which a Trocken¬ is medium, which supply in the form of ring tablet 2 reliably protects the drug before Feuchtigkeits¬ shot. Since the cap 5 at Aus¬ exchange of the inhalation tube 1 and the drug stoffvor- rats at the same time as a closure cap of a Aerosol¬ generators used remains the drying agent 6 stock over the entire consumption period during Arzneistoff¬ and is only after its consumption by a new unit from inhalation tube 1, ArzneistoffVor¬ rat 2, the closure cap 5 and desiccant 6 er¬ sets. Interference from mechanical and chemical comminuted safe custody of the drug-shaped body in the inventive packaging unit is ge Mäss Fig. 1 completed by a base member 3 in which the inhalation tube 1 "device snap-in" is snapped 4 by means of a. A hermetic Ver¬ circuit of the entire packaging is achieved by a second

11

"Snap closure cap 5 reach device between the base element 3 and Ver¬.

The effectiveness of the drug stoffZube¬ reitung invention with regard reproducible generation of respirable fine particles is documented by the figures 2 and 3. FIG. It is in both cases original writer diagrams of Partikelgrößenver¬ division by the volume fractions and indeed in Fig. 2 of the non mikroni overbased starting mixture of 25% Sal¬ butamol and 75% lactose. In Fig. 3, the Partikel¬ represented size distribution of the mechanically generated aerosol from a ring tablet according to the invention from this mixture, the advantageous after be¬ Sonders Production was compacted homogeneously isosta Steam pressing at 250 MPa.

As is apparent from Fig. 2, the Par¬ extends tikelverteilung the starting mixture over a very large range between 0 to about 200Λ> * n particulate or granulate diameter. In actual respirable range between 0.5 to about 10A ** only very small amounts are starting material represented in this training. In Fig. 3, the Partikelvertei is lung after mechanical aerosol generation from a ring tablet shown which was prepared from the above-mentioned starting mixture. As can be seen, are in this range only inhaled, respirable particles range from 0.5 to 7, 5 t <m, wherein the total amounts of - depending on the drug - between about 10 to 5000 m Mikrogra ein¬ are adjustable.

Claims

claims
1. A cemented drug supply for the mechanical production of inhalable particles of active substance, characterized in that it has an isotropic solid structure.
2. drug supply according to claim 1, characterized gekenn¬ characterized in that this is designed as a thick-walled annular body.
3. drug supply according to claim 1 or 2, characterized in that this has at least one of folic constricting pharmaceutical active substance groups:
Respiratory medicines from the group of betamimetics as fenoterol, Sjlbu- ta ol Salmetarol
Terbutaline and their seh pharmakologi active
Enantiomers, from the group of Antichol Inergi ka, such as ipratropium bromide lergika from the group of steroids, such as budesonide, R-budesonide, beclomethasone, fluticasone from the group of anti al how Dinatriumchromo- glycat, Ketodifen from the group of PAF -Antagon i th as Gingkolide, WEB-2086, and the therapeutics amiloride, furosemide, potassium Kanak-activators, leukotriene inhibitors and Bradi- kinin antagonists. Peptidhor one such as insulin, calcitonin, desmopressin drugs for substance abuse such as nicotine, methadone, Levomethadon
SUBSTITUTE SHEET Narkoaralgetica / Neuroleptanalgetika as Buprenorphi n, dehydrocodeine
Alkaloids such Scopola in
Chemotherapeuti ka as pentamidine
4. drug supply according to claim 3, characterized gekenn¬ characterized in that the active substances with effective neutral carriers such as lactose, glucose, mannitol or sodium chloride are combined.
5. The process for producing solidified Arzneistoff¬ inventories with an isotropic solid structure, characterized in that these material formulations are prepared by isostatic pressing, preferably at pressures ranging between 50 and 500 megapascals, in medicine.
6. The process for producing solidified Arzneistoff¬ inventories with an isotropic solid structure, characterized in that they are made from pharmaceutical compositions by injection molding plastified ed masses.
7. The process for producing solidified Arzneistoff¬ inventories with an isotropic solid structure, characterized in that these pharmaceutical preparations are prepared from the melting process.
8. The process for producing solidified Arzneistoff¬ inventories with an isotropic solid structure, characterized in that these pharmaceutical preparations are made from die-cast.
SUBSTITUTE SHEET
9. orrat drug according to any one of claims 1 to 5, characterized in that it is contained in an insertable in an inhaler holder.
10. drug supply according to claim 9, characterized characterized gekenn¬ that this bevor¬ with the holder in a light, air and moisture-proof container is guess.
11. drug supply according to claim 9 and 10, characterized in that the container is part of the cap of the inhaler Verschlu߬.
SUBSTITUTE SHEET
PCT/EP1993/001158 1992-12-23 1993-05-11 Compacted drug body for use in the mechanical generation of inhalable active-substance particles WO1994014490A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
DE4243649 1992-12-23
DEP4243649.4 1992-12-23

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
AU40666/93A AU4066693A (en) 1992-12-23 1993-05-11 Compacted drug body for use in the mechanical generation of inhalable active-substance particles

Publications (1)

Publication Number Publication Date
WO1994014490A1 true WO1994014490A1 (en) 1994-07-07

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Country Status (3)

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JP (1) JPH06339513A (en)
AU (1) AU4066693A (en)
WO (1) WO1994014490A1 (en)

Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4429707C1 (en) * 1994-08-04 1996-02-01 Bernhard Dipl Ing Hugemann Inhaler with an integrated, solidified, annular drug tablet
WO1999029432A1 (en) * 1997-12-05 1999-06-17 Palas Gmbh Method and device for producing a solid aerosol
WO1999061003A1 (en) * 1998-05-27 1999-12-02 Euroceltique S.A. Drug delivery system comprising a tightly compacted solid medicament stock
WO2001085174A1 (en) * 2000-05-12 2001-11-15 Chiesi Farmaceutici S.P.A. Formulations containing a glucocorticoid drug for the treatment of bronchopulmonary diseases
US6964759B2 (en) 2000-02-22 2005-11-15 Chiesi Farmaceutici S.P.A. Formulations containing an anticholinergic drug for the treatment of chronic obstructive pulmonary disease
US6967017B1 (en) 1999-07-23 2005-11-22 Chiesi Farmaceutici S.P.A. Formulations of steroid solutions for inhalatory administration
US7018618B2 (en) 2000-05-22 2006-03-28 Chiesi Farmaceutici S.P.A. Stable pharmaceutical solution formulations for pressurized metered dose inhalers
DE102005028696A1 (en) * 2005-06-21 2006-12-28 Pulmotec Gmbh Use of auxiliary material comprising calcium stearate, magnesium stearate, stearic acid, cromoglycic acid and/or di-sodium-cromoglycate, active substance and carrier material, for adjusting abrasion firmness of hardened preparation
US7220737B1 (en) 1997-09-04 2007-05-22 Novoneuron, Inc Noribogaine in the treatment of pain and drug addiction
US7223381B2 (en) 1998-11-25 2007-05-29 Chiesi Farmaceutici S.P.A. Pressurised metered dose inhalers (MDI)
US7297344B1 (en) 1999-05-27 2007-11-20 Euro-Celtique, S.A. Preparations for the promotion of wound healing in the upper respiratory tract and/or ear
US7300667B1 (en) 1999-05-27 2007-11-27 Euro-Celtique, S.A. Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract
US7381402B2 (en) 2004-02-27 2008-06-03 Chiesi Farmaceutici S.P.A. Stable pharmaceutical solution formulations for pressurized metered dose inhalers
EP1941868A2 (en) 2000-02-28 2008-07-09 PharmaKodex Limited Improvements in or relating to the delivery of oral drugs
US7468194B1 (en) 1999-05-27 2008-12-23 Euro-Celtique, S.A. Preparations for the application of anti-inflammatory agents
US7601336B2 (en) 1997-06-13 2009-10-13 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
US7696178B2 (en) 2001-07-02 2010-04-13 Chiesi Farmaceutici S.P.A. Optimised formulation of tobramycin for aerosolization
US7754710B2 (en) 1997-09-04 2010-07-13 Novoneuron, Inc. Noribogaine in the treatment of pain and drug addiction
US8362007B1 (en) 2010-05-11 2013-01-29 Demerx, Inc. Substituted noribogaine
US8381721B2 (en) 2008-09-26 2013-02-26 Oriel Therapeutics, Inc. Dry powder inhalers with dual piercing members and related devices and methods
US8550071B2 (en) 2008-09-26 2013-10-08 Oriel Therapeutics, Inc. Inhalers with airway disks having discrete airway channels and related disks and methods
US8637648B1 (en) 2010-06-22 2014-01-28 Demerx, Inc. Compositions comprising noribogaine and an excipient to facilitate transport across the blood brain barrier
US8646446B2 (en) 2008-10-01 2014-02-11 Oriel Therapeutics, Inc. Dry powder inhalers with rotating piercing mechanisms and related devices and methods
US8741891B1 (en) 2010-06-22 2014-06-03 Demerx, Inc. N-substituted noribogaine prodrugs
US8765737B1 (en) 2010-05-11 2014-07-01 Demerx, Inc. Methods and compositions for preparing and purifying noribogaine
US8802832B2 (en) 2010-06-22 2014-08-12 Demerx, Inc. Compositions comprising noribogaine and an excipient to facilitate transport across the blood brain barrier
US8859764B2 (en) 2011-01-26 2014-10-14 Demerx, Inc. Methods and compositions for preparing noribogaine from voacangine
US8877921B2 (en) 2012-01-25 2014-11-04 Demerx, Inc. Synthetic voacangine
US8887722B2 (en) 2008-09-26 2014-11-18 Oriel Therapeutics, Inc. Inhaler mechanisms with radially biased piercers and related methods
US8940728B2 (en) 2012-12-20 2015-01-27 Demerx, Inc. Substituted noribogaine
US9045481B2 (en) 2012-12-20 2015-06-02 Demerx, Inc. Substituted noribogaine
US9050427B2 (en) 2008-09-30 2015-06-09 Oriel Therapeutics, Inc. Dry powder inhalers with multi-facet surface deagglomeration chambers and related devices and methods
US9051343B2 (en) 2011-12-09 2015-06-09 Demerx, Inc. Phosphate esters of noribogaine
US9150584B2 (en) 2012-01-25 2015-10-06 Demerx, Inc. Indole and benzofuran fused isoquinuclidene derivatives and processes for preparing them
US9358237B2 (en) 2010-07-23 2016-06-07 Demerx, Inc. Noribogaine compositions
US9394294B2 (en) 2010-05-11 2016-07-19 Demerx, Inc. Methods and compositions for preparing and purifying noribogaine
US9550789B2 (en) 2014-06-18 2017-01-24 Demerx, Inc. Halogenated indole and benzofuran derivatives of isoquinuclidene and processes for preparing them
US9586954B2 (en) 2010-06-22 2017-03-07 Demerx, Inc. N-substituted noribogaine prodrugs
US9617274B1 (en) 2011-08-26 2017-04-11 Demerx, Inc. Synthetic noribogaine
US9783535B2 (en) 2012-12-20 2017-10-10 Demerx, Inc. Substituted noribogaine

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Cited By (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4429707C1 (en) * 1994-08-04 1996-02-01 Bernhard Dipl Ing Hugemann Inhaler with an integrated, solidified, annular drug tablet
US7601336B2 (en) 1997-06-13 2009-10-13 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
US8420058B2 (en) 1997-06-13 2013-04-16 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
US7220737B1 (en) 1997-09-04 2007-05-22 Novoneuron, Inc Noribogaine in the treatment of pain and drug addiction
US8178524B2 (en) 1997-09-04 2012-05-15 Demerx, Inc. Noribogaine in the treatment of pain and drug addiction
US7754710B2 (en) 1997-09-04 2010-07-13 Novoneuron, Inc. Noribogaine in the treatment of pain and drug addiction
WO1999029432A1 (en) * 1997-12-05 1999-06-17 Palas Gmbh Method and device for producing a solid aerosol
WO1999061003A1 (en) * 1998-05-27 1999-12-02 Euroceltique S.A. Drug delivery system comprising a tightly compacted solid medicament stock
US8142763B2 (en) 1998-11-25 2012-03-27 Chiesi Farmaceutici S.P.A. Pressurized metered dose inhalers (MDI) containing a solution comprising ipratropium bromide, HFA propellant, and co-solvent and comprising a container with a specific internal surface composition and/or lining
US7223381B2 (en) 1998-11-25 2007-05-29 Chiesi Farmaceutici S.P.A. Pressurised metered dose inhalers (MDI)
US7347199B1 (en) 1998-11-25 2008-03-25 Chiesi Farmaceutici S.P.A. Pressurised metered dose inhalers (MDI)
US7300667B1 (en) 1999-05-27 2007-11-27 Euro-Celtique, S.A. Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract
US7297344B1 (en) 1999-05-27 2007-11-20 Euro-Celtique, S.A. Preparations for the promotion of wound healing in the upper respiratory tract and/or ear
US7468194B1 (en) 1999-05-27 2008-12-23 Euro-Celtique, S.A. Preparations for the application of anti-inflammatory agents
US6967017B1 (en) 1999-07-23 2005-11-22 Chiesi Farmaceutici S.P.A. Formulations of steroid solutions for inhalatory administration
US6964759B2 (en) 2000-02-22 2005-11-15 Chiesi Farmaceutici S.P.A. Formulations containing an anticholinergic drug for the treatment of chronic obstructive pulmonary disease
EP1941868A2 (en) 2000-02-28 2008-07-09 PharmaKodex Limited Improvements in or relating to the delivery of oral drugs
WO2001085174A1 (en) * 2000-05-12 2001-11-15 Chiesi Farmaceutici S.P.A. Formulations containing a glucocorticoid drug for the treatment of bronchopulmonary diseases
US7018618B2 (en) 2000-05-22 2006-03-28 Chiesi Farmaceutici S.P.A. Stable pharmaceutical solution formulations for pressurized metered dose inhalers
US7939502B2 (en) 2001-07-02 2011-05-10 Chiesi Farmaceutici S.P.A. Optimised formulation of tobramycin for aerosolization
US8168598B2 (en) 2001-07-02 2012-05-01 Chiesi Farmaceutici S.P.A. Optimised formulation of tobramycin for aerosolization
US7696178B2 (en) 2001-07-02 2010-04-13 Chiesi Farmaceutici S.P.A. Optimised formulation of tobramycin for aerosolization
US7381402B2 (en) 2004-02-27 2008-06-03 Chiesi Farmaceutici S.P.A. Stable pharmaceutical solution formulations for pressurized metered dose inhalers
DE102005028696A1 (en) * 2005-06-21 2006-12-28 Pulmotec Gmbh Use of auxiliary material comprising calcium stearate, magnesium stearate, stearic acid, cromoglycic acid and/or di-sodium-cromoglycate, active substance and carrier material, for adjusting abrasion firmness of hardened preparation
US8887722B2 (en) 2008-09-26 2014-11-18 Oriel Therapeutics, Inc. Inhaler mechanisms with radially biased piercers and related methods
US8381721B2 (en) 2008-09-26 2013-02-26 Oriel Therapeutics, Inc. Dry powder inhalers with dual piercing members and related devices and methods
US9597465B2 (en) 2008-09-26 2017-03-21 Oriel Therapeutics, Inc. Methods of operating and fabricating inhalers with airway disks having discrete airway channels
US9795749B2 (en) 2008-09-26 2017-10-24 Oriel Therapeutics, Inc. Dry powder inhalers with dual piercing members and methods of operating same
US8985103B2 (en) 2008-09-26 2015-03-24 Oriel Therapeutics, Inc. Dry powder inhalers with dual piercing members
US8671938B2 (en) 2008-09-26 2014-03-18 Oriel Therapeutics, Inc. Inhalers with airway disks having discrete airway channels and related disks and methods
US8550071B2 (en) 2008-09-26 2013-10-08 Oriel Therapeutics, Inc. Inhalers with airway disks having discrete airway channels and related disks and methods
US9050427B2 (en) 2008-09-30 2015-06-09 Oriel Therapeutics, Inc. Dry powder inhalers with multi-facet surface deagglomeration chambers and related devices and methods
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