Download Inhaler Devices

Inhaler Devices
Dr. Dane EDIGER
Uludağ University School of Medicine
Departement of Allergy
1
Inhalation Devices
Aim
To make aerosol from the drugs solution or
solid particles
1-Metered dose inhaler
2-Dry powder inhaler
3-Nebulizer
2
Definition of an aerosol
• Aero air
• Sol solution
• Liquid or solid suspensions into gas
medium
• Particles which are sufficiently small so as
to remain airborne for a considerable
period of time
3
• Lower aerosol size
• Upper aerosol size
.
0,001 µm
0,01 µm
0,1 µm 1 µm
10 µm
100 µm =0,1 mm
4
History of Inhaled Therapy
•
•
•
•
China, India, Middle-east
Hippokrattes
Galenos
4000 years ago: the smoke of ephedra
sinica was used to asthma therpy
• Smoke of Atropa belladona, Datura
stramonium
• Sulphur, arsenic, menthol, timol, eucaliptus
5
Modern age
• Metered dose inhaler 1956 Medihaler
• Dry powder inhaler
1960
• Multidose dry powder inhaler 1970
• 440 million boxes aerosols per year are
manufactured in the world
6
Why Inhalation Therapy?
• Targeted delivery of medication to the
lungs
• Rapid onset of action
• Smaller doses
• Less systemic and GI adverse effects
• Relatively comfortable
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PHARMACOKINETICS OF INHALED
DRUGS
Oropharynx
absorbtion
Lung absorbtion
Gastrointestinal
absorbtion
SYSTEMIC CIRCULATION
Vena porta
Hepatic inactivation
first pass effect
Urine elimination
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Adverse Effects
INH KS
INH B2
AGONIST
LOCAL
SYSTEMIC
Candidiasis
Dysphonia
Adrenal suppression
Growth retardation
(large doses)
Sympathetic
stimulation- tremor
Tachicardia
Hypokalemia
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Deposition of particles
> 5 µ impaction
1-5 µ sedimentation
< 1 µ like gas
10
Hypothesis from available data
Particle size
(microns)
Regional
deposition
>5
Mouth /
oesophageal
region
No clinical
effect
Absorption
from GI
tract if
swallowed
1–5
Upper / central
airways
Clinical
effect
Subsequent
absorption
from lung
<1
Peripheral
airways / alveoli
Efficacy
Some local
clinical
effect
Safety
High
systemic
absorption
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Lung deposition of drug
• Particle
–
–
–
–
size
shape
particle density
solid or liquid phase
• Type of inhalation
device
• Tecknique
• Airway obstruction
• Drug molecule
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4 Types of Inhaler Devices
• MDI/ DPI
• Jet /Ultrasound
nebulizer
• Small volumes
• Ready for use
• Stable obstructive
disease
• High fill volume > 1 ml
• Preparation required
• Severe respiratory
insufficiency (asthma
attack, COPD exac.,
CF)
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Pressured Metered Dose Inhalers
(pMDI)
•
•
•
•
Canister
Small reservoir
Metering reservoir
After pressure
valve drug sprays
• Aerosol
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Metered Dose Inhalers (pMDI)
• Canister
– Propellent gas (liquid under
pressure)
• Drug
– Dissolved or solid microparticules
into the gas
• Surfaktant
– Physical stabilisation
– Prevent clustering
– Decreas valv friction
• Drug layer is surface of liquid
propellent because more
lightweight, it must be rinced
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before use
Propellant
Chloro fluoro carbon (CFC)
–
–
–
–
CFC (freon gas)
CFC not flammable
Vapouring after spray
Particules continue
movement
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Propellant
Hydro fluoro alcan (HFA)
– Not include chloride
– Not disturbe Ozone layer
– İt influence on global heating
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MDI advantages
• Rapid application
• Handling
• Multidose
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MDI Disadvantages
• Hand-breathe coordinations
• İneffective use in poor ventilated
patiens
• Oropharyngeal deposition and local
side effects
• Not include dosimeter
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Hand-breathe coordinations
Autohaler
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MDI spacer
Decrease of oropharyngeal
deposition
Proposing inhaled CS
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MDI spacer
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Not include dosimeter
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Chest. 2002;121:871-876
The SmartMist was 100%
accurate, The Doser CT was
94.3% and MDILog was 90.1%
All three devices are sufficiently
accurate to monitor adherence in
most clinical settings
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Freon (CFC)
• Cold freon effect
• Oropharyngeal irritation, cough and
bronchospasm
• Harmfull for ozone layer
• Cardiac arrhytmia
• Less effective in cold climate
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MDI with HFA (CFC-free)
• Evohaler
• Salbutamol
• Flutikazon
• Budesonide Formoterol
• BDP
• Levalbuterol
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Therapeutic Ratio of Hydrofluoroalkane and
Chlorofluorocarbon Formulations of
Fluticasone Propionate
Fowler SJ., Chest, 2002
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Dry powder inhaler (DPI)
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Classification of Dry Powder Inhalers,
Based on Design and Function
Single-Dose Devices
Aerolizer
formoterol capsule
HandiHaler tiotropium capsule
Multiple Unit-Dose Devices
Diskhaler
fluticasone blister
zanamivir blister
Multiple-Dose Devices
Turbuhaler budesonide
Turbuhaler budesonide/formoterol
Diskus
salmeterol
Diskus
salmeterol/fluticasone
single
single
cassette
cassette
reservoir 200
reservoir 120
blister strip 60
blister strip 60
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Dry powder inhaler (DPI)
Multi doses
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Lung depostion form a budesonide Turbohaler
measured by gamma scintigraphy
Borgstrom et al Eur Respir J 1994;7:69-73
Total lung deposition
(% of inhaled dose)
30L/min
60L/min
Inspiration Rate
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FAST vs SLOW INHALATION USING 500mcg
TERBUTALINE via A TURBOHALER
(n=10 ASTHMATICS)
FEV1, MMFR & PEFR
FOR FAST > SLOW
BUT N.S.
LUNG DEPOSITION
(% OF THE DOSE)
60L/min
30L/min
Newman et al Int J Pharm 1991
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Dry powder inhaler (DPI)
single dose
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Device dependent factors
 Device
• pMDI:
• Portability, Treatment time, Drug
preparation, Reproducibility, Coordination,
Actuation, Drug availability, Holding
chamber, Propellant
• DPI:
• Breath-actuation, Coordination, Portability,
Treatment time, Dose counters, Flow
requirement, Drug availability,
Resistance, Costs.
• Aerosol
• Particle size, Velocity, Physico-chemical
characteristics
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Patient dependent factors
 Age
•
•
•
•
co-operation
compliance
airway anatomy
breathing patterns
 Disease
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Lung Deposition of ICS
Dose to the lungs
MDIs
Ciclesonide
Fluticasone
Budesonide
BDP HFA MDI
52%
16%
5-12%
51%
DPIs
Different flow rates
Budesonide Turbuhaler
Budesonide Novolizer
Budesonide Airmax 28-30%
One flow rate
Budesonide Clickhaler
Fluticasone Diskus
17-39%
19-32%
27%
13%
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TOTAL LUNG DEPOSITION AND DISTRIBUTION
OF TERBUTALINE IN THE LUNG FOLLOWING
INHALATION USING A TURBOHALER AND MDI
CENTRAL ZONE
TOTAL LUNG
INTERMEDIATE ZONE
% DEPOSITION
PERIPHERAL ZONE
MDI
TURBOHALER
Borgstrom & Newman Int J Pharm 1993;97:47-53
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Mean intra-subject variability
% coefficient of
variability
60
52.0%
50
40.4%
40
42.4%
35.9%
31.8%
30
20
10
0
Volumatic
Easi-Breathe
Accuhaler
Turbohaler
Evohaler
pMDI
Device
Aswania O et al. J Aerosol Med 2004; 17(3): 231-8.
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•a review looking systematically at the clinical effectiveness
and cost-effectiveness of inhaler devices in asthma and
COPD
39
• Only randomized controlled trials (RCT)
• (394 trials- years 1982 to 2001) assessing
– inhaled corticosteroid,
– B2-agonist
– anticholinergic agents delivered by
•
•
•
•
MDI,
MDI with a spacer/holding chamber,
nebulizer,
DPI
• Only 59 (primarily those that tested B2agonists) proved to have usable data
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Summaries and Results
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Results
• None of the pooled meta-analyses showed a
significant difference between devices in any
efficacy outcome in any patient group for
each of the clinical settings that was
investigated
• The adverse effects that were reported were
minimal and were related to the increased
drug dose that was delivered
• Each of the delivery devices provided similar
outcomes in patients using the correct
technique for inhalation
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B2 agonist ED /ICU
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Aerosol Delivery of Short-Acting B2-Agonists
in the Hospital Emergency dept
• SABA in the ED: nebulizer = MDIs with spacer
– improving pulmonary function
– reducing symptoms of acute asthma
– in both adult and paediatric patients (quality of evidence: good).
• SABA in the ED: DPI = nebulizer = MDIs with spacer
– in adults
– data is inadequate (quality of evidence: low)
• Heart rate  in the ED : nebulizer > MDIs with spacer
(quality of evidence: good)
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Recommendations
• 1. Both the nebulizer and MDI with spacer are
appropriate for the SABA in the ED
– Quality of evidence: good
– net benefit: substantial
– strength of recommendation: A
• 2. Data for DPIs are limited
– Quality of evidence: low
– net benefit: none
– strength of recommendation: I
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The appropriate selection of a particular
device in this setting
–
–
–
–
–
the patient’s ability to use the device correctly
the preferences of the patient for the device
the availability of the drug/device combination
the compatibility between the drug and the delivery device
the lack of time or skills to properly instruct the patient in the use
of the device or to monitor the appropriate use
– the cost of the therapy
– the potential of reimbursement
– Quality of evidence: low
– net benefit: substantial
– Strength of recommendation: B
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Aerosol Delivery of SABA in the
Inpatient Hospital Setting
• SABA in the inpatient: nebulizer = MDI with spacer
– pulmonary function response (quality of evidence: good)
• Recommendations:
• 1. Both nebulizers and MDIs with spacer are appropriate for
use in the inpatient setting
– Quality of evidence: good
– Net benefit: substantial
– strength of recommendation: A
• 2. Data for DPIs are limited
– Quality of evidence: low
– net benefit: none
– strength of recommendation: I
49
Aerosol Delivery of SABA for Asthma in the
Outpatient Setting
• SABA in the adult and paediatric outpatient: MDI = DPI
– pulmonary function responses
– symptom scores
– heart rate
– (quality of evidence: good)
• SABA in the outpatient: MDI =MDI with spacer
– pulmonary function responses (quality of evidence: low)
• Data for nebulizers are limited
– (quality of evidence: low)
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Recommendations
• 1. Both the MDI with or without spacer and
DPI are appropriate for the SABA in outpatient
– Quality of evidence: good
– net benefit: substantial
– strength of recommendation: A
• 2. Data for DPIs are limited
– Quality of evidence: low
– net benefit: none
– strength of recommendation: I
51
Inhaled Corticosteroids for Asthma
• Same dose of the same corticosteroid for adult
patients with asthma in the outpatient: DPI or
MDI with spacer
– Pulmonary function response
– symptom scores (quality of evidence: good)
• Patient preference: DPI > MDI with spacer
– 2 studies (quality of evidence: good).
• Data for incidence of oral candidiasis ??
– (quality of evidence: low)
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Recommendations
• 1. Both the MDI with spacer and DPI are
appropriate for the inhaled KS in outpatient
– Quality of evidence: good
– net benefit: substantial
– strength of recommendation: A
• 2. Data for DPIs are limited
– Quality of evidence: low
– net benefit: none
– strength of recommendation: I
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Inhaled B2-Agonists and
Anticholinergic Agents for COPD
• Inhaled B2-Agonists and Anticholinergic in
the outpatient of COPD: MDIs with or
without spacer = DPI = nebulizer
– pulmonary function responses (quality of
evidence: good)
• Heart rate : albuterol by nebulizer >
MDI
– (quality of evidence: good)
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Recommendations:
• MDI, with or without spacer, nebulizer,
and DPI are all appropriate for the delivery
of inhaled B2- agonist and anticholinergic
agents for the treatment of COPD in the
outpatient
– Quality of evidence: good
– net benefit: substantial
– strength of recommendation: A
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• Cihazların göreceli etkinlikleri birini
diğerine tercih etmek için yeterli bir
üstünlük sağlamamakta
• Bu durum hastaya özel cihazı belirlemenin
bir sorun olmadığı anlamına da
gelmemektedir
• Tüm bu çalışmalar bu cihazları iyi
kullanabilen hastalarda yapılmıştır
56
IDEAL INHALER
57
Respimat
58
Newman SP J Aerosol Med 1999
VENTAİRA
Non-uniform dispersion of
medication delivered by dry
powder inhaler (DPI)
Uniform dispersion of
medication delivered by
Ventaira
Pharmaceutical’s device.
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DirectHaler TM Pulmonary
• Kuru toz inhaler
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