SMBE 4323 GROUP 4 NEBULIZER PRESENTED BY: 1. MUHAMAD REZA NAZRIN BIN A RAHMAN 2. LAILA FADHILLAH BINTI ULTA DELESTRI 3.GOH VOON HUEH

WHAT IS A NEBULIZER? A drug delivery device used to deliver medication in the form of aerosol (mist) inhaled into the lungs Uses oxygen, compressed air or ultrasonic power to break up the liquid medications into aerosol droplets then deliver the dose directly into the lungs

Produce loud noise and heavy FOCUS Jet Nebulizer/Compressed-Air Nebulizer/Atomizer The most common use in hospital for patients with chronic respiratory disease. Connected to compressor, that causes compressed air flow at higher velocity through the liquid medicine then turned into aerosol. Advantages Low operational cost Disadvantages Produce loud noise and heavy

Schematic of typical nebulizer system. SYSTEM DESCRIPTION Schematic of typical nebulizer system.

SYSTEM DESCRIPTION Gas Source The medication inside the medication cup. Help patient breath normally. Delivery System Mouthpiece The place where the liquid medicine turn into mist.

SYSTEM DESCRIPTION Aerosol Reservoir Eg. a reservoir bag or piece of reservoir tubing. Additional volume devoted especially to aerosol storage Without reservoir part, 60% of the drug might loss into the air.

SYSTEM DESCRIPTION Flow Reservoir To accommodate the patient’s inspiratory flow when it exceeds the source gas flow. Give infinite air flow. Without FR, if the patient breath too deep, the mouthpiece cannot depressurize, therefore there will be not airflow. The tube is simply be a communication to the atmosphere, so it will not become a problem about the airflow. Reservoir bag can inflate and deflate, so it will produce airflow into patient lung,

SYSTEM DESCRIPTION Patient Drug is inhale into respiratory pathway.

Presence of liquid medicine On/Off button Presence of liquid medicine Medication in the cup is a must. Either premix or mix by user. Example: Anti immonoglobulin E (Anti IgE) Albuterol Actonocholinergics INPUT OF NEBULIZER

Aerosol / Mist of Medicine OUTPUT OF NEBULIZER Pressurized gas is supply into the medication cup through a jet. The liquid medicine will ride along with the gas stream. Liquid will sheared and become unstable, and break into droplets. Baffle preventing the stream to spread into particular direction. causing larger particles to return to the liquid reservoir. 99% particle may be returned to the liquid reservoir. Only small particle (mist) will be transfer to patient respiratory system. Aerosol / Mist of Medicine 3. Because of high surface tension force.

SYSTEM PROCESS

Nebulizer Working Principle Pressurized air flows into reservoir. Pass through the small narrow opening (orifice). Air leaves with high velocity. Leaves jet while mixing with liquid medication. High velocity, breaks up the liquid into tiny droplets and create mist

1 2 Air Pump 3 basic forces of nature to move a liquid. As the moving pump part (impeller)begins to move, air is pushed out of the way. The movement of air creates a partial vacuum (low pressure) which can be filled up by more air. This is similar to sucking on a straw. A partial vacuum is created in your mouth when you suck on the straw. The liquid is pushed up the straw because of the pressure differences between your mouth and the atmosphere. At sea level, mother nature exerts a pressure of 14.7 psi all around us. If one end of a tube is placed in water and a perfect vacuum is applied to the other end, that 14.7 psi could hold a column of water 33.9 feet high. This is only obtainable at sea level and with a perfect vacuum. In nature, movement is from more dense to less dense. Weather systems are tracked as high pressures move toward low pressures. liquid under high pressure will move to an area of less pressure if a path is provided.

4 Air Pump 5 4. The centrifugal pump works in the same way as sucking on the straw. As the engine starts, the impeller turns which forces the water around it out of the pump's discharge port. The partial vacuum created, allows the earth's air pressure to force water up the suction hose (straw), and into the suction (inlet) side of the pump to replace the displaced water. 5. Eg of water pump

Air Pump Bernoulli’s Principle Rotating impeller to rotate the air flow Spins the air (flow in slow in velocity, high in pressure) Then discharge the air flow at nozzles with low pressure and high velocity. Using turbine or motor to rotate impeller.

Nebulizer Air Pump

Exhale and Inhale

PERFORMANCE TESTING & MEASUREMENTS

Droplet size of the aerosol Amount of dose delivered Characteristics of good performance of nebulizers : Rapid and efficient delivery of drug to the correct part of the respiratory tract Critical factors affecting the performance of nebulizer: Droplet size of the aerosol Amount of dose delivered

TYPES OF PERFORMANCE TESTING Provide real-time measurement of the size of droplets (average median diameter) produced Laser Diffraction Assessing the delivered amount of aerosol in fine-droplet fraction (%) Cascade Impaction Droplet size decreased with increasing compressed gas flow rate Compressor Flow Rate Measured the delivered dose of inhalation solution Aerosol Output Analysis

1. Laser Diffraction Measurements can be made at varying the flow rate without affecting the accuracy of the results obtained Analysis size distribution of droplets ranging from 0.25µm to 875µm A 100-mm range lens: To detect the particles size An inhaler attachment: To provide constant delivery of mist across the laser beam and also an enclosed system within the mist from the nebulizer Air flow rate was controlled by the software (Sympatec) The aerosol that passed across the laser beam was withdrawn by a vacuum extraction system: To avoid data error Spraytec (Malvern Instruments) Helos/Br Inhaler (Sympatec)

Results and measurements: Laser Diffraction Figure 1 shows the effect of increasing the breathing rate on Dv50 delivered by the nebuliser The Dv50 decreases as the bpm rate increases, especially during the mid-point of the breathing profile Figure 2 shows changes in the median particle size (Dv50) and concentration delivered by a breath-assisted nebuliser (using 10bpm) Initial inhalation: Low concentration delivered & Large droplet size Midpoint inhalation: Droplet size decreases & aerosol concentration increases rapidly Figure 1 To have different breathing profiles, use sinusoidal breath simulator to mimic different breathing pattern of person Why need different flow rates? Changes in the air flow rate can be used to control the delivered particle size Output of nebulizer changes in relation to inhalation profile Measurement droplet size: Dv50 aka Median Droplet Size Measurement breathing rate: bpm aka Breath Per Minute Figure 2

2. Cascade Impaction At a flow rate of 28.3 L/min over a 6 min period High-pressure liquid chromatography mobile phase: To extract solution (arformoterol) from the various stages of the cascade impactor The fine-droplet fraction is calculated: the sum of the arformoterol dose on stages 3 through “filter” divided by the sum of the arformoterol dose on “throat” through “filter” of the cascade impactor Fine-droplet dose in nominal dose also calculated: [(delivered dose / fine-droplet fraction)/100] Anderson Cascade Impaction Schematic Diagram of Cascade Impaction

Results and measurements: Cascade Impaction Figure 1 shows the set up of the performance testing and how amount of stages in cascade impactor can measure different sizes of aerosol (droplets) Figure 2 shows the result of different brand of nebulizers can have different Fine-Droplet Fraction and Fine-Droplet Dose in % of Nominal Dose The higher the % of Fine-Droplet Fraction, the smaller the size of droplets produced by the nebulizer The higher % of Fine-Droplet Dose in Nominal Dose, the greater the amount of dose delivered through the nebulizer Figure 1 Fine-Droplet : Size of droplets < 4.7µm Fine Droplet Dose in Nominal Dose: Measure % of dose delivered among the dose droplet fraction Figure 2

3. Compressor Flow Rate The air supply provides primary source of atomisation thus able in controlling droplet sizes Flow rate measurements: Measured by using a rotameter Rotameter is placed in line with nebulizer/compressor system Measurements were taken at 1-minute and 6-minute intervals Rossmax Nebulizer Tester

Results and measurements: Compressor Flow Rate Figure 1 shows where the changes in droplet size distribution delivered by the nebulizer for different compressed air flow rates (using breathing rate 20bpm) A gradual reduction in the overall droplet size distribution is observed as the gas flow rate increases Figure 1 Measurement flow rate: L/min

Comparison between Laser Diffraction and Cascade Impaction

4. Aerosol Output Analysis Applied vacuum-assisted constant flow rate of 28.3 L/min The aerosol output was collected in a glass Dreschel type apparatus High-pressure liquid chromatography mobile phase solution: Extract solution (arformoterol) from the Dreschel-type apparatus The amount arformoterol extracted measured via : high-pressure liquid chromatography The residual amount of arformoterol contained in the nebulizer also extracted and measured using: high-pressure liquid chromatography The remaining volume in the nebulizer bowl after extraction was measured: using weight

Results and measurements: Aerosol Output Analysis Amount of solution (medication) delivered Amount of residual (medication) Remaining volume in the nebulizer