PH2107 - Nebulisers

Question 1

What is a nebuliser?

Answer 1

A device which transforms a solution or suspension of medication into aerosol that is optimal for deposition into the lower airway

Question 2

How many doses are delivered by a nebuliser?

Answer 2

One, over multiple breaths

Question 3

What is the difference between a nebuliser and a pMDI and a Respimat Soft Mist inhaler?

Answer 3

A pMDI and a Respimat Soft Mist inhaler have dose metering capability

Question 4

What are nebulisers driven by?

Answer 4

Compressed gas or oxygen, or by ultrasonically vibrating crystals

Question 5

What are nebulisers used for?

Answer 5

When high doses of reliever medication are required

• emergency rooms
• ambulances

Question 6

What are the advantages of using nebulisers?

Answer 6

• many patients can’t master the correct use of metered dose inhalers or dry powder inhalers (elderly and young children)
• some prefer the nebuliser over other aerosol generating devices
• possible to deliver virtually any drug and in virtually any dose, usually the first choice device during early phase clinical trials

Question 7

What formulations can be used with a nebuliser?

Answer 7

• aqueous solutions

- suspensions

Question 8

Describe aqueous systems used in nebulisers

Answer 8

• well established excipients in low concetrations
• dilute with 0.9% NaCl to adjust tonicity
• acids or bases to adjust pH
• need to be isotonic
• unit dose ampoules now standard

Question 9

Give examples of suspensions that can be used with nebulisers

Answer 9

Drugs with low water solubility

• glucocorticosteroids
• micronized particles
• nanoparticles

Question 10

Give two examples of types of nebuliser

Answer 10

• air jet

- electronic

Question 11

How does an air jet nebuliser work?

Answer 11

Compressed gas is used to drive drug formulation through a spray nozzle

Question 12

Describe the features of an air jet nebuliser

Answer 12

Traditional
- constant output - same output rate during inhalation and exhalation
- more than 50% dose unavailable to patient
Breath-enhanced
- quantity of aerosol generated during inhalation increased by control of air flow through device
Interval
- only generated aerosol during inhalation

Question 13

How does an electronic nebuliser work?

Answer 13

Creates aerosols from ultrasonic vibration

Question 14

Describe the features of an electronic nebuliser

Answer 14

Ultrasonic nebulisers
- aerosol formed from fountain above a vibrating piezoelectric crystal
Vibrating membrane nebulisers
- aerosol formed by extrusion of drug solution via a vibrating membrane, mesh or grid
Adaptive aerosol delivery
- aerosol delivery matches individual breathing patterns

Question 15

What are the features of nebulisers?

Answer 15

1. Several minutes to aerosolise a single dose
2. Compressed gas causes evaporation and cooling
   - temperature of solution falls
   - nebuliser solution becomes concentrated
3. End of nebulisation marked by sputtering
4. Device is not empty after nebulisation
   - dead volume may comprise more than half the dose

Question 16

What are the advantages of air jet nebulisers?

Answer 16

• relatively inexpensive
• simple formulation of drugs (including biotechnology products). Suspensions, emulsions, liposomes, other micro-particulates are also feasible
• well accepted (especially in hospitals and for infants)
• drug input can be halted at any time during dosing

Question 17

What are the disadvantages of air jet nebulisers?

Answer 17

• dose to lung not readily controlled
• lengthy nebulisation time - compliance?
• large drug loss (up to 50% of starting volume left in nebuliser)
• large variability in nebuliser performance
• designed primarily for aqueous solutions (suspensions may show greater variability)
• evaporative cooling and concentration (drug precipitates)
• aerosol may be released into the atmosphere (contamination?)
• not highly portable
• noisy

Question 18

What are the features of electronic nebulisers?

Answer 18

Compared to air jet nebulisers
- similar dead volume of liquid
- broadly similar output characteristics (model dependent)
- usually quieter and more compact than air jet nebuliser
Temperature of nebuliser fluid tends to rise
- potential damage to thermally sensitive compounds
Do not atomise suspensions and viscous solution efficiently

Question 19

What are the features of vibrating membrane nebulisers?

Answer 19

Droplets formed at the membrane are small enough for delivery direct to the patient
- no baffles needed
- no recycle of liquid within the device
- low dead volumes (< 1ml)
- more efficient aerosol delivery
- short nebulisation time
Relatively compact, portable and energy efficient
Battery operated

Question 20

What is a DPI?

Answer 20

Dry Powder Inhaler

Question 21

What are the features of a Pressurised Metered Dose Inhaler?

Answer 21

• portable
• convenient
• multidose

Question 22

What are the limitations of a pMDI?

Answer 22

• difficult to co-ordinate
• requires propellant
• dose < 1mg per actuation

Question 23

What are the opportunities for Dry Powder Inhalers?

Answer 23

• mostly breath-actuated (passive devices)
• propellant free
• higher doses than pMDIs

Question 24

What size particles are in a DPI formulation?

Answer 24

Drug particles < 5um required

- BUT micronised drug particles highly cohesive