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Inhaler Devices Dr. Dane EDIGER Uludağ University School of Medicine

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Presentation on theme: "Inhaler Devices Dr. Dane EDIGER Uludağ University School of Medicine"— Presentation transcript:

1 Inhaler Devices Dr. Dane EDIGER Uludağ University School of Medicine
Departement of Allergy

2 Inhalation Devices Aim
To make aerosol from the drugs solution or solid particles 1-Metered dose inhaler 2-Dry powder inhaler 3-Nebulizer

3 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

4 . Lower aerosol size Upper aerosol size
0,001 µm ,01 µm 0,1 µm 1 µm 10 µm 100 µm =0,1 mm

5 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

6 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

7 Why Inhalation Therapy?
Targeted delivery of medication to the lungs Rapid onset of action Smaller doses Less systemic and GI adverse effects Relatively comfortable Obstrüktif havayolu hastalıklarının tedavisinde en etkili ve güvenli yoldur İnhaler kısa etkili B2 agonistle aynı etkiyi oluşturmak için gereken oral formun dozu kat fazladır İnhaler kısa etkili B2 agonistle oluşan serum ilaç düzeyi oral formla alınana göre 100 kat daha düşüktür Oral yolla verilen ilaçlarda GİS intoleransı ve sistemik yan etki riski daha yüksektir İnhaler kısa etkili B2 agonist etkisi 15 dak da, oral formun etkisi 1-2 saatte ortaya çıkar With COPHIT the future of the inhaler is bright. can be investigated computationally, permitting evaluation of 'what if' scenarios. Investigate the effect of changing device dimensions, or the impact of a spacer on efficacy of drug delivery.

Oropharynx absorbtion Lung absorbtion Gastrointestinal absorbtion İnh KS ler lipidde eridikleri için oral emilebilirler, Beta 2 agonistler ise akcaiğer dokusunda emilmektedirler. Figure 1 shows that following inhalation some of the emitted dose is deposited into the lungs and the remainder impacts in the oropharyngeal area followed by swallowing (1,2). The inhaled dose is then delivered into the systemic circulation following absorption from the lungs and gastro-intestinal tract. A fraction of the dose is eliminated by muco-ciliary clearance followed by swallowing. Bronchodilators, corticosteroids and antibiotics deposited into the lungs will provide a local therapeutic effect. Other drugs can be formulated such that they are deposited into the alveolar area for good systemic delivery. These drugs can be delivered using the pulmonary route to provide their systemic effect when only the injection route is available because of problems with gastro-intestinal administration. When drug is delivered to the systemic circulation the body identifies it as an unwanted visitor and therefore removes the drug. This removal is either by excretion of the unchanged drug in the urine or metabolism to a more water soluble (and usually inactive) derivative that can be removed by the renal route. The renal route is the major pathway to remove either unchanged or metabolised drug but there are other pathways (eg. bile). Drug that is swallowed but not absorbed is eliminated in the faeces. SYSTEMIC CIRCULATION Vena porta Hepatic inactivation Urine elimination first pass effect

9 Adverse Effects LOCAL SYSTEMIC INH KS INH B2 AGONIST Candidiasis
Dysphonia Adrenal suppression Growth retardation (large doses) INH B2 AGONIST Sympathetic stimulation- tremor Tachicardia Hypokalemia

10 Deposition of particles
> 5 µ impaction 1-5 µ sedimentation < 1 µ like gas

11 Hypothesis from available data
> 5 Particle size (microns) Regional deposition Efficacy Safety Mouth / oesophageal region No clinical effect Absorption from GI tract if swallowed > 5 Particle size (microns) Regional deposition Efficacy Safety 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 Some local clinical effect High systemic absorption

12 Lung deposition of drug
Particle size shape particle density solid or liquid phase Type of inhalation device Tecknique Airway obstruction Drug molecule

13 4 Types of Inhaler Devices
MDI/ DPI Small volumes Ready for use Stable obstructive disease Jet /Ultrasound nebulizer High fill volume > 1 ml Preparation required Severe respiratory insufficiency (asthma attack, COPD exac., CF)

14 Pressured Metered Dose Inhalers (pMDI)
Canister Small reservoir Metering reservoir After pressure valve drug sprays Aerosol

15 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 before use

16 Propellant Chloro fluoro carbon (CFC)
CFC (freon gas) CFC not flammable Vapouring after spray Particules continue movement

17 Propellant Hydro fluoro alcan (HFA)
Not include chloride Not disturbe Ozone layer İt influence on global heating Salbutamol, salmeterol ve flutikazon için itici gaz farklılık yaratmazken BDP için HFA içeren ÖDİ CFC içeren daha küçük tanecikli ve daha az lokal yan etkili bulunmuştur

18 MDI advantages Rapid application Handling Multidose

19 MDI Disadvantages Hand-breathe coordinations
İneffective use in poor ventilated patiens Oropharyngeal deposition and local side effects Not include dosimeter Yanlış kullanım oranı % Eğitime rağmen %20 kalıyor

20 Hand-breathe coordinations Autohaler

21 MDI spacer Decrease of oropharyngeal deposition Proposing inhaled CS

22 MDI spacer

23 Not include dosimeter

24 Chest. 2002;121: 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

25 Freon (CFC) Cold freon effect
Oropharyngeal irritation, cough and bronchospasm Harmfull for ozone layer Cardiac arrhytmia Less effective in cold climate

26 MDI with HFA (CFC-free)
Evohaler Salbutamol Flutikazon BDP Levalbuterol Budesonide Formoterol

27 Therapeutic Ratio of Hydrofluoroalkane and Chlorofluorocarbon Formulations of Fluticasone Propionate
Fowler SJ., Chest, 2002

28 Dry powder inhaler (DPI)

29 Classification of Dry Powder Inhalers, Based on Design and Function
Single-Dose Devices Aerolizer formoterol capsule single HandiHaler tiotropium capsule single Multiple Unit-Dose Devices Diskhaler fluticasone blister cassette zanamivir blister cassette Multiple-Dose Devices Turbuhaler budesonide reservoir 200 Turbuhaler budesonide/formoterol reservoir 120 Diskus salmeterol blister strip 60 Diskus salmeterol/fluticasone blister strip 60

30 Dry powder inhaler (DPI) Multi doses

31 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 L/min Inspiration Rate

(n=10 ASTHMATICS) FEV1, MMFR & PEFR FOR FAST > SLOW BUT N.S. LUNG DEPOSITION (% OF THE DOSE) 60L/min L/min Newman et al Int J Pharm 1991

33 Dry powder inhaler (DPI) single dose

34 Device dependent factors
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

35 Patient dependent factors
Age co-operation compliance airway anatomy breathing patterns Disease

36 Lung Deposition of ICS Dose to the lungs MDIs DPIs Ciclesonide 52%
Fluticasone 16% Budesonide % BDP HFA MDI 51% DPIs Different flow rates Budesonide Turbuhaler 17-39% Budesonide Novolizer 19-32% Budesonide Airmax 28-30% One flow rate Budesonide Clickhaler 27% Fluticasone Diskus 13%


38 Mean intra-subject variability
% coefficient of variability 60 52.0% 50 42.4% 40.4% 40 35.9% 31.8% 30 20 10 Volumatic Easi-Breathe Accuhaler Turbohaler Evohaler pMDI Device Aswania O et al. J Aerosol Med 2004; 17(3):

39 a review looking systematically at the clinical effectiveness and cost-effectiveness of inhaler devices in asthma and COPD

40 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 B2-agonists) proved to have usable data

41 Type 1 Trials: Device Performance Under Conditions of Actual Clinical Use
example 1-To compare the effect of a B2-agonist agent delivered by nebulizer, DPI, and/or MDI in patients presenting to the emergency dept. with acute asthma improvement in lung function oxygenation hospital admission rate To compare the effect of inhaled corticosteroids delivered by different devices over a period of weeks daily asthma symptoms, B2-agonist use daily peak flow measurement

42 Type 2 Trials: Device Performance in the Clinical Laboratory Setting
To compare drug delivery to the lungs and the clinical response to drugs administered by different devices under carefully controlled clinical laboratory conditions To establish dose-response curves for each of the devices To estimate differences in the clinical potency of the devices (relative potency or potency ratio) and a confidence interval The results; “1 actuation (or µg of drug) delivered from ‘device A’ is equivalent to ‘X’ number of actuations (or µg) delivered from ‘device B.’

43 Summaries and Results

44 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

45 B2 agonist ED /ICU

46 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)

47 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

48 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

49 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

50 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)

51 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

52 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)

53 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

54 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)

55 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

56 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


58 Respimat Newman SP J Aerosol Med 1999

59 VENTAİRA Non-uniform dispersion of medication delivered by dry powder inhaler (DPI) Uniform dispersion of medication delivered by Ventaira Pharmaceutical’s device.

60 DirectHaler TM Pulmonary
Kuru toz inhaler

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