Question

Aerosol Drug Therapy (in typed form)

1. What is MMAD?
2. Define emitted dose.
3. Define respirable dose. What is the micron size contained in the respirable dose?
4. Why is particle size so important in aerosol drug therapy?
5. What does heterodisperse mean?
6. There are three mechanisms of aerosol deposition in the lung. What are they? Define each.

Answer 1

1) Aerosol drug therapy use of an aerosol for respiratory care in the treatment of bronchopulmonary disease. The major purpose of this is the delivery of medications or humidity or both to the mucosa of the respiratory tract and pulmonary alveoli. Agents delivered by aerosol therapy may act in a number of ways: (1) to relieve spasm of the bronchial muscles and reduce edema of the mucous membranes, (2) to render bronchial secretions more liquid so that they are more easily removed, (3) to humidify the respiratory tract, and (4) to administer antibiotics locally by depositing them in the respiratory tract.
2) MMAD- Mass median aerodynamic diameter

The MMAD divides the aerosol size distribution in half. It is the diameter at which 50% of the particles of an aerosol by mass are larger and 50% are smaller.
3) The drug mass should be reported rather than the percentage of emitted dose (or other derived parameter).The inhaler invention therefore provides advantages over other inhalers, especially, when a repeatable emitted dose is important and generally, where contamination and hygiene in the flow channel is an issue as is the case with multi-dose inhalers.
4) Respirable Dose- The total dose emitted by a nebulizer, MDI, or Spacer does not, by itself, provide a meaningful approximation of how much medication will be deposited in the patients lungs. Other factors such as particular size, geometric standard deviation, plume geometry and spreay pattern can have very significant effects. Therefore, it is often necessary to combine these variables in a manner that can approximate what amount of medication is actually deposited in the lungs. Piper Medical has experience using a large number of different techniques, the most common of which is to determine the amount of medication present in the delivered aerosol that has a particle size between 0.5 and 5 microns. This is the technique that the FDA uses almost exclusively.
Drug deposited within the upper airways of patients using dry powder inhalers does not contribute to the therapeutic effect but can result in unwanted local side effects and, when swallowed, may contribute to systemic effects. A chamber has been devised which uses the centrifugal force generated by the Turbohaler to remove large "non-respirable" particles with a view to minimising deposition in the upper airway. An in vitro study was performed to determine whether such a chamber could reduce the dose contained in coarse particles without having a significant effect on the "respirable dose". METHODS: The mouthpiece of a 200 micrograms Turbohaler was modified to allow a small volume chamber to be attached. The particle size distribution generated by the Turbohaler was assessed using a multi-stage liquid impinger with a flow rate of 60 l/min. The quantity of drug on each stage was quantified using an ultraviolet spectrophotometric technique. For each experiment 10 actuations were used to ensure adequate quantities of drug on each stage. Particles depositing on stages 3 + 4 have a diameter of < 6.8 microns and are arbitrarily referred to as the "respirable dose". The particle size distribution obtained using the Turbohaler (n = 10) was compared with that from the Turbohaler+ chamber (n = 11). RESULTS: The addition of the chamber resulted in the mean (SD) dose contained in larger "non-respirable" particles depositing on stages 1 + 2 being reduced from 52.2 (12.3) to 29.6 (6.9) micrograms per actuation. However, the chamber did not affect the "respirable" dose. The dose contained in particles with a diameter of < 6.8 microns from the standard Turbohaler was 91.1 (8.9) micrograms compared with 82.4 (18.6) micrograms when used with the chamber.

CONCLUSIONS: These results indicate that it is possible to devise an effective particle size selection device for the Turbohaler. It may be possible to produce such devices for other dry powder inhalers, although the design would need to be tailored to each particular device.

5) Appropriate particle sizes are important to enable adequate concentrations at the target site. Particle size also determines the mechanism of deposition in the respiratory system. Particles that distribute deep in the smaller airways are reported to have up to 70 % deposition efficiency.

6) Describing a colloid in which the particles are of different sizes.

7) The primary aerosol deposition mechanisms may include inertial impaction, sedimentation, diffusion, interception, and electrostatic effects. The contribution of thesedeposition mechanisms is a function of particle size and flow rate in a given region of respiratory tract.
Deposition Mechanisms

It is widely accepted that the mainmechanisms affecting aerosol transport and deposition in the human lunginclude inertial impaction, gravitational sedimentation, and Brownian diffusion, and to a lesser extent turbulent flows, interception, and electrostatic precipitation.