NEBULIZER AND DRY POWDER INHALATION : NEBULIZER AND DRY POWDER INHALATION Presented by
Viral D. Jagiwala
Mr. Ravish Patel Introduction : Introduction Basic factors important in the delivery of aerosolized agents to the lung:
1. Aerosol itself,
2 The pathophysiology of the human respiratory tract(e.g., breathing pattern and airway geometry), and
3. The delivery device. Ideal Nebulizer : Ideal Nebulizer 1. A minimum residual volume (< 0.5 mL)
2. Aerosol delivered only during inhalation
3. No waste aerosol released to the environment
4. Aerosol delivered with a droplet size distribution suitable for pulmonary or tracheobronchial deposition
5. Small and portable: similar to the more popular pMDIs and DPIs (and ideally no more expensive)
6. Rapid treatment time, quiet and unobtrusive in use
7. Finally, perhaps also a means to monitor patient compliance Principle : Principle Medium is liquid solution
Gas enters in nebulizer under pressure
Acclerated through orifice
High velocity air creation(low pressure creation)
Draws liquid through capillary tubing in to gas stream
Distribution can be modified by baffle
Certain particle gets released other will recycled. Meassurement of nebulization function : Meassurement of nebulization function Gravimetric Measurements
“Standing Cloud” Importance of Breathing Pattern : Importance of Breathing Pattern In Vitro Measurement of Inhaled Mass for Adult and Pediatric Aerosol Delivery : In Vitro Measurement of Inhaled Mass for Adult and Pediatric Aerosol Delivery By
Standing claud technique.
Harvard pump Harvard pump : Harvard pump Measuring Particle Size during Nebulization : Measuring Particle Size during Nebulization By cascade impactor.
Light scattering device. Cascade impactor : Cascade impactor Components of NEBULIZER : Components of NEBULIZER Route of Inhalation : Route of Inhalation The nose is an efficient filter, and patients should be encouraged to inhale aerosols through their mouths. Up to 300% more aerosols reaches the lungs if a nebulized aerosol is inhaled via the mouth rather then the nose. NEBULIZER TECHNOLOGY : NEBULIZER TECHNOLOGY PRINCIPLE FOR NEBULIZATION TECHNOLOGY:
A. Jet Nebulizers
1. Constant-output (or unvented),
2. Breath-enhanced (or vented), and
3. Breath-activated nebulizers.
B. Ultrasonic Nebulizers
C. Passive Mesh-Type Piezoelectric Nebulizer
D. Vibrating Membrane-Type Piezoelectric Systems
E. Electrohydrodynamic Systems Jet nebulizer : Jet nebulizer Ultrasonic Nebulizer : Ultrasonic Nebulizer Passive Mesh-Type Piezoelectric Nebulizer : Passive Mesh-Type Piezoelectric Nebulizer Vibrating Membrane-Type Piezoelectric Systems : Vibrating Membrane-Type Piezoelectric Systems Components of the Nebulizer Charge : Components of the Nebulizer Charge Solutions
Suspensions Assessment of Performance of Nebulizer Technology : Assessment of Performance of Nebulizer Technology A. British Standard on In Vitro Assessment of Nebulizer Performance
B. European Standard on In Vitro Assessment of Nebulizer Performance. REGULATORY ISSUES : REGULATORY ISSUES 510k submission procedure How to Give the Nebulizer Treatment : How to Give the Nebulizer Treatment 1. Place the compressor near a power source and where you can reach the on/off switch.
2. Always wash your hands before preparing each treatment and start with a clean nebulizer cup.
3. Measure the correct dose of medications and place the medicine in the nebulizer cup.
4. Attach the mouthpiece to the nebulizer cup.
5. Connect tubing from the compressor to the bottom of the nebulizer cup.
6. Sit in relaxed, upright position. Turn on air compressor.
7. Close lips around mouthpiece, place mouthpiece on top of tongue and breathe in the aerosol mist slowly through the mouth.
8. Breathe out slowly.
9. Continue steps 6-8 until medication is gone or you hear a sputtering sound.
10. Turn off air compressor.
11. Disconnect tubing from bottom of nebulizer cup. Care and Cleaning of the Nebulizer System Equipment : Care and Cleaning of the Nebulizer System Equipment Daily use: After each treatment, rinse the nebulizer cup and mouthpiece with hot tap water. At the end of each day, wash the cup and mouthpiece in hot tap water with liquid detergent. Rinse well. Allow to air dry. Do not wash the tubing. If the tubing gets wet on the inside, get new tubing
To disinfect: This should be done at least once a week. There are several choices for disinfecting the nebulizer cup and mouthpiece: 1) wash in a dishwasher if the water temperature gets above 158 degrees for greater than 30 minutes; 2) boil in water for 5 minutes; 3) soak in 70% isopropyl alcohol for 5 minutes and rinse with sterile water; or 4) soak in 3% hydrogen peroxide for 30 minutes and rinse with sterile water.
Care of the compressor: Dry Powder inhalation : Dry Powder inhalation Dry powder inhalers are bolus drug delivery devices that contain solid drug, suspended or dissolved in a non polar volatile propellant or in dry powder inhaler that is fluidized when the patient inhales.
Dry powder inhalers have a number of advantages over othermethods of pulmonary drug delivery, for example, direct delivery of drug into deep lungs utilizing the patient’s respiration and are increasingly being explored as a mechanism for the delivery of on the systemic drugs. Advantages : Advantages Propellant free design
Less need for patient coordination
Less potential for formulation problems (formulation stability)
Less potential for extractables from device components
Environmental sustainability Disadvantages : Disadvantages Dependency on patient’s inspiratory flow rate and profile
Device resistance and other design issues
Greater potential problems in dose uniformity
Less protection from environmental effects and patient abuse
More expensive than pressurized metered dose inhalers
Not available world wide
Development and manufacture more complex/expensive IDEAL DRY POWDER INHALERS : IDEAL DRY POWDER INHALERS Effective dosing
Uniform dose through life
Targeted and optimized delivery
controlled respirable fraction
inhalation of dose-independent aerosol generation
bolus of aerosol available at the beginning of an inhalation
Operable at low inhalation flow rates Slide 28: Efficient device
Good environmental production
Design optimized by the use of, for example, practical engineering, manufacturing innovation.
In-process controls for quality
Compact, portable, cheap and reusable
Clear comparative data for complaint Slide 29: Easy to use
Patient feedback of dose administration FORMULATION : FORMULATION DPI formulation must undergo flow, fluidization, and deaggregation.
Formulation of API with or without carriers.
Integration of the formulation into device. Production and classification of the primary API : Production and classification of the primary API techniques such as supercritical fluid technology, crystallization by ultra-sonic precipitation, and preparation of low density porous particles.
A common method of particle production is spray drying since it is a single step process resulting in primary API particles with spherical morphology, with a controllable size distribution. Formulation of the API in binary or ternary systems : Formulation of the API in binary or ternary systems A: Jet mill.
B: Pin mill.
C: Ball mill. DPI DESIGN : DPI DESIGN PRINCIPLE OF OPERATION : PRINCIPLE OF OPERATION currently available DPI devices : currently available DPI devices (A) AerolizerTM,
(J) HandihalerTM EVALUATION : EVALUATION Appearance
Identity(chromatography and spectroscopy)
Drug related impurities
Drug content per unit dose/dose delivery
Particle size analysis/respirable dose
Stimulated patient use
*Through device use
Reusable Vs disposable reliability testing CONCLUSION : CONCLUSION The number of diseases that are being considered candidates for the aerosol therapy has increased substantially. Until recently, asthma was only the clear example of a disease that could be treated via aerosol delivery to lungs. We now consider it possible to treat not only asthma and chronic obstructive pulmonary diseases but also systemic disorders such as diabetes, cancer, neurobiological disorders and other pulmonary diseases such as cystic fibrosis and pulmonary infectious diseases. REFERENCES/BIBLIOGRAPHY : REFERENCES/BIBLIOGRAPHY GERALD C. SMALDONE, PETER N. LESOUEF, Nebulization The Device and Clinical Considerations. in DRUG DELIVERY TO THE LUNG, (2002) Marcel Dekker, Inc. New York Basel pp-239.
JOHN H. DENNIS OLA NERBRINK, New Nebulizer Technology, in DRUG DELIVERY TO THE LUNG, (2002) Marcel Dekker, Inc. New York Basel pp-303.
Martin Knoch, Warren Finlay, Nebulizer Technologies in Modified-Release Drug Delivery Technology (2003), Marcel Dekker, Inc. New York Basel pp-849
Michael T. Newhouse, Drug Delivery: Pulmonary Delivery, in Encyclopedia of PHARMACEUTICAL TECHNOLOGY Third Edition 2007, Informa Healthcare USA, Inc. pp-1279. Slide 41: Hartwig Steckel, Fadi Eskandar, European Journal of Pharmaceutical Sciences, Volume 19, Issue 5, August 2003, pp- 443-455.
Laurent Vecellio, Paul Kippax, Stephane Rouquette, Patrice Diot, International Journal of Pharmaceutics, Volume 371, Issues 1-2, 17 April 2009, pp- 99-105.
Orvar Swenson, Luis Grana, Thomas Hausam, Journal of Pediatric Surgery, Volume 6, Issue 5, October 1971, pp- 554-558.
Antoine Minne, Hélène Boireau, Maria Joao Horta, Rita Vanbever,European Journal of Pharmaceutics and Biopharmaceutics, Volume 70, Issue 3, November 2008, pp- 839
Paul M. Young, Daniela Traini, and Stephen Edge, Advances in Pulmonary Therapy in Advanced Drug Formulation Design to Optimize Therapeutic Outcomes. Pp-01 Slide 42: TAHANK YOU