NZ797404B2 - An inhalable formulation of fluticasone propionate and albuterol sulfate - Google Patents
An inhalable formulation of fluticasone propionate and albuterol sulfateInfo
- Publication number
- NZ797404B2 NZ797404B2 NZ797404A NZ79740421A NZ797404B2 NZ 797404 B2 NZ797404 B2 NZ 797404B2 NZ 797404 A NZ797404 A NZ 797404A NZ 79740421 A NZ79740421 A NZ 79740421A NZ 797404 B2 NZ797404 B2 NZ 797404B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- formulation
- dry powder
- fluticasone propionate
- port
- swirl chamber
- Prior art date
Links
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61K31/569—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone substituted in position 17 alpha, e.g. ethisterone
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
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- 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
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
- A61M11/001—Particle size control
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- 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
- A61M15/0001—Details of inhalators; Constructional features thereof
- A61M15/0005—Details of inhalators; Constructional features thereof with means for agitating the medicament
- A61M15/0006—Details of inhalators; Constructional features thereof with means for agitating the medicament using rotating means
- A61M15/0008—Details of inhalators; Constructional features thereof with means for agitating the medicament using rotating means rotating by airflow
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- 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
- A61M15/0001—Details of inhalators; Constructional features thereof
- A61M15/0021—Mouthpieces therefor
- A61M15/0025—Mouthpieces therefor with caps
- A61M15/0026—Hinged caps
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- 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
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- 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
- A61M15/0048—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 in a plane, e.g. on diskettes
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- 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
- A61M15/0065—Inhalators with dosage or measuring devices
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- 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
- A61M15/0065—Inhalators with dosage or measuring devices
- A61M15/0068—Indicating or counting the number of dispensed doses or of remaining doses
- A61M15/007—Mechanical counters
- A61M15/0071—Mechanical counters having a display or indicator
- A61M15/0078—Mechanical counters having a display or indicator on a strip
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- 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
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- 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
- A61M2205/00—General characteristics of the apparatus
- A61M2205/75—General characteristics of the apparatus with filters
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- 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
- A61M2206/00—Characteristics of a physical parameter; associated device therefor
- A61M2206/10—Flow characteristics
- A61M2206/16—Rotating swirling helical flow, e.g. by tangential inflows
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- 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
- A61M2207/00—Methods of manufacture, assembly or production
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- 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
- A61P11/06—Antiasthmatics
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- 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
- A61P11/08—Bronchodilators
Abstract
This invention relates to a fixed-dose dry powder inhalation formulation comprising fluticasone propionate and albuterol sulfate, together with an a-lactose monohydrate carrier. In the formulation, the albuterol sulfate stabilises fluticasone propionate.
Claims (21)
1. Use of a dry powder inhalable formulation consisting of fluticasone propionate, albuterol sulfate and a-lactose monohydrate in preparation of a medicament for long-term treatment of asthma or COPD or treatment of acute bations of asthma or COPD, wherein the powder inhalable formulation is a rescue medication.
2. The use as claimed in claim 1, wherein a total daily dose of fluticasone propionate does not exceed 1,000 µg.
3. The use as claimed in claim 1 or claim 2, for treatment of acute exacerbations of asthma or COPD, wherein the dry powder inhalable formulation is a pro re nata rescue medication.
4. The use as claimed in any one of claims 1-3, wherein the dry powder inhalable formulation has an extended in-use shelf life when compared to a composition consisting of fluticasone propionate and alactose monohydrate.
5. A process for preparing a dry powder ble formulation consisting of fluticasone propionate, albuterol sulfate and a-lactose monohydrate, sing the steps of: (i) ing a e of fluticasone propionate and a-lactose monohydrate to form a first blend; (ii) ing a mixture of albuterol sulfate and a-lactose monohydrate to form a second blend; and (iii) mixing the first blend and the second blend to form the formulation.
6. The process as claimed in claim 5, further comprising (iv) conditioning the formulation.
7. The s as claimed in claim 6, wherein ioning the formulation includes: (a) exposure of the formulation to 65%RH / 30°C for a duration of 21 to 36 days; (b) exposure of the ation to 65%RH / 30°C for a duration of 28 to 35 days; or (c) exposure of the formulation to 65%RH / 30°C for a duration of 28 days.
8. The process as claimed in claim 6 or claim 7, wherein the formulation is loaded into a formulation reservoir of a dry powder inhaler, and the dry powder inhaler is placed on a tray prior to the performance of (iv).
9. The process as claimed in claim 6 or claim 7, n the formulation is loaded into a formulation reservoir of a dry powder inhaler, and the dry powder inhaler is placed on a tray and the inhaler and tray are wrapped with a polyethylene wrap prior to the performance of (iv).
10. A process for preparing a dry powder inhalable formulation consisting of fluticasone propionate, albuterol sulfate and a-lactose monohydrate, comprising the steps of: (i) preparing a mixture of fluticasone propionate, albuterol sulfate and a-lactose monohydrate; and (ii) conditioning the mixture, wherein the formulation has an extended in-use shelf life when ed to a ition consisting of fluticasone propionate and a-lactose monohydrate.
11. The process as claimed in claim 10, wherein step (ii) includes: (a) exposure of the ation to 65%RH / 30°C for a duration of 21 to 36 days; or (b) exposure of the formulation to 65%RH / 30°C for a duration of 28 to 35 days; or (c) exposure of the formulation to 65%RH / 30°C for a duration of 28 days.
12. The process as claimed in claim 10 or claim 11 wherein the formulation is loaded into a formulation oir of a dry powder inhaler, and the dry powder inhaler is placed on a tray prior to the performance of step (ii).
13. The process as claimed in claim 10 or claim 11, wherein the formulation is loaded into a ation reservoir of a dry powder inhaler, and the dry powder inhaler is placed on a tray and the inhaler and tray are wrapped with a polyethylene wrap prior to the performance of step (ii).
14. The use as claimed in any one of claims 1-3, wherein the dry powder inhalable formulation is contained in a dry powder inhaler sing a cyclone deagglomerator for breaking up agglomerates of the dry powder inhalable formulation.
15. The use as claimed in claim 14, n the cyclone deagglomerator comprises: an inner wall defining a swirl chamber extending along an axis from a first end to a second end; a dry powder supply port in the first end of the swirl chamber for providing fluid communication n a dry powder ry passageway of the inhaler and the first end of the swirl chamber; at least one inlet port in the inner wall of the swirl chamber adjacent to the first end of the swirl chamber providing fluid communication between a region exterior to the deagglomerator and the first end of the swirl chamber; an outlet port providing fluid communication between the second end of the swirl chamber and a region exterior to the deagglomerator; and vanes at the first end of the swirl chamber extending at least in part radially dly from the axis of the chamber, each of the vanes having an oblique surface facing at least in part in a direction transverse to the axis; whereby a breath induced low pressure at the outlet port causes air flows into the swirl chamber through the dry powder supply port and the inlet port.
16. The use as claimed in claim 14 or claim 15, wherein the dry powder inhaler comprises: a sealed reservoir including a dispensing port; a channel communicating with the dispensing port and including a pressure relief port; a conduit providing fluid communication between an interior of the sealed oir and the pressure relief port of the channel; and a cup assembly movably received in the channel and including, a recess d to receive formulation when aligned with the dispensing port, a first sealing surface adapted to seal the dispensing port when the recess is unaligned with the dispensing port, and a second sealing e adapted to sealing the pressure relief port when the recess is aligned with the dispensing port and unseal the pressure relief port when the recess is unaligned with the dispensing port.
17. The use as claimed in any one of claims 1-3, wherein the particle size distribution of the inhaled albuterol sulfate is d10 = 0.4-1.0 µm, d50 = 1.0-3.0 µm, d90 = 2.5-9.0 µm and NLT99% <10 µm.
18. The use as claimed in any one of claims 1-3, wherein the particle size distribution of the d a-lactose drate is d10 = 10-25 µm, d50 = 85-105 µm, d90 = 140-180 µm, NLT99% <300 µm and 1.5-8.5% <10 µm, or d10 = 19-43 µm, d50 = 50-65 µm, d90 = 75-106 µm, NLT99% <300 µm and 1.55% <10 µm.
19. The use as claimed in any one of claims 1-3, wherein the particle size distribution of the fluticasone propionate is d10=0.4-1.0 µm, d50=1.0-3.0 µm, d90=2.5-7.5 µm and NLT99%<10 µm.
20. The use as claimed in claim 3, for treatment of asthma in patients with step 2 asthma as defined by the Global Initiative for Asthma (GINA) 2005 guidelines.
21. The use as claimed in claim 3, for ent of COPD in patients with airflow limitation severity GOLD 2 as defined by the tee for the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines. 3 ‘_____—_____¢~._§ “d —; z: 110 me 110 133 ' 103 , 105 1 1 D - 1GB _ 1 1D on 1 Position 2 Posnion 3 Back
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB2012742.9A GB202012742D0 (en) | 2020-08-14 | 2020-08-14 | An inhalable medicament |
| PCT/EP2021/072718 WO2022034241A1 (en) | 2020-08-14 | 2021-08-16 | An inhalable formulation of fluticasone propionate and albuterol sulfate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ797404A NZ797404A (en) | 2025-10-31 |
| NZ797404B2 true NZ797404B2 (en) | 2026-02-03 |
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