Aerosols - Delivery Systems And Formulation For Inhalation 2

Question 1

What is an aerosol?

Answer 1

Dispersion of solid particles or liquid droplets in a gas

Question 2

What three times of inhalers are there?

Answer 2

Nebulisers
Pressurised metered dose inhalers
Dry powder inhalers

Question 3

Which is the most widely used inhaler and why?

Answer 3

PMDI - most convenient

Question 4

What is a nebuliser?

Answer 4

Aqueous drug solution / suspension aerolised into droplets - energy provided by compressed air or ultrasound

Question 5

What is a pMDI?

How is compliance improved by pMDI?

Answer 5

Pressurised metered dose inhaler
Drug formulated in a liquefied gas under pressure
Aerosol formed by evaporation of gas at atmospheric pressure
More compliance because works same from device to device and fewer steps

Question 6

What is a DPI?

Answer 6

Dry powder inhaler
Drugs normally with other solid excipients in dry powder state
Aerosolisation by patient

Question 7

What are the two types of nebuliser?

Answer 7

Jet Nebuliser (or atomiser)
Ultrasonic Nebuliser

Question 8

How does a Jet Nebuliser work?

Answer 8

Air from compressor forced through narrow hole to give high velocity air stream
High velocity air breaks drug solution / suspension into droplets for inhalation
Baffles are used to remove larger particles

Question 9

How does an Ultrasonic Nebuliser work?

Answer 9

Piezoelectric crystal emits high frequency signal
Breaks drug solution / suspension into droplets for inhalation
Lighter and quieter than a jet nebuliser

Question 10

What is a drawback of Ultrasound Nebuliser?

Answer 10

Some drugs are degraded by the ultrasound

Question 11

How is a nebuliser used?

Answer 11

Patient breathes normally into the face mask or mouth piece

Question 12

Advantages of a nebuliser

Answer 12

Aqueous drug solutions used (very simple for soluble drugs)
No hand lung coordination needed so good for elderly and children
No controlled inhalation manoeuvre required
Large doses of drug and mixtures not normally available can be given
Relatively low cost
Visible mist can reassure the patient

Question 13

Disadvantages of nebulisers

Answer 13

Not fully portable
Equipment not fully regulated yet
Lengthy nebulisation time
Low efficiency (much of solution is wasted)
Solution concentrates as water evaporates
Insoluble drugs require solubilisation
Some suspensions are difficult to nebulise
Susceptible to microbiological contamination

Question 14

Criteria for a pMDI container

Answer 14

Withstand high pressure 
Robust 
Light in weight 
Inert 
Made of aluminium or stainless steel (steel better for higher pressures)

Question 15

What is a pMDI metering valve?

Answer 15

Ensures accurate and reproducible volume of drug formulation is delivered
Delivered from continuous spray valves
20-100 microlitres

Question 16

Properties of a pMDI propellant ?

Answer 16

Liquid under pressure of 3-5 atmospheres
Gas at atmospheric pressure and ambient temperature
It’s vapour pressure must stay constant - dose uniformity
Non flammable and non toxic
Chemically inert

Question 17

Discuss CFC propellant

Answer 17

Ozone depleting
Banned
Responsible for the cold - freon effect

Question 18

Discuss hydrofluoroalkanes as propellant

Answer 18

Drugs needed to be reforms later due to different properties of HFA compared to CFC
New valve materials developed

Question 19

If a drug is soluble in propellant how is it formulated into a pMDI?

Answer 19

Solubilised in propellant

Ethanol might be added as a co-solvent

Question 20

If a drug is insoluble in propellant how is it formulated into a pMDI?

Answer 20

Micronised drug particles are suspended in propellant
Surfactants added to increase suspension stability
Most common pMDI formulation

Question 21

What is needed to form an aerosol?

Answer 21

Source of energy

Question 22

What is the main concern for each dose from a pMDI?

Answer 22

Each dose is correct and the volume of suspension is homogenous

Question 23

Why are surfactants added to the formulation of a pMDI?

Answer 23

Improve stability / homogeneity of the suspension

Aid the formulation of a flocculated suspension (easily redispersible)

Question 24

What are the four main problems facing the suspension in a pMDI inhaler?

Answer 24

Sedimentation (non-homogeneity)
Flocculation (reversible aggregation)
Caking - difficult to redisperse
Particle size growth by Otswald ripening (deposition in the lungs reduced)

Question 25

What are the ideal criteria for suspension of pMDI?

Answer 25

Slow flocculation Slow sedimentation Easy redisperse I.e partially flocculated suspension

Question 26

What other add on excipients can be used in pMDI?

Answer 26

``` Flavours Sweeteners Lubricants Density modifiers Antioxidants ```

Question 27

How do spacer devices help with inhalation of pMDI?

Answer 27

Increase lung deposition - delay between actuation and inhalation - decrease the velocity of the spray - more time for propellant to evaporate

Question 28

Why is the dose inhaled by a patient reduced when using a spacer and pMDI?

Answer 28

Deposition in the device due to electrostatic charges causing droplets to stick to the chamber

Question 29

pMDI advantages

Answer 29

Compact portable robust convenient Multi dose Short treatment time Consistent formation / operation for all pMDIs Good dose content uniformity Good protection against moisture and pathogens Inexpensive

Question 30

pMDI disadvantages

Answer 30

Usually no breathe actuation Low lung deposition No dose counter (to record used) Only low doses can be delivered (

Question 31

What is a Dry a Powder Inhaler?

Answer 31

Dry powder, no solvent is involved

Question 32

Main components of a DPI

Answer 32

Drug powder or blend with excipients Drug reservoir or pre-metered doses (cartridge, blister, capsules) Body of the device Cap to protect powder from dust / moisture

Question 33

How is patients inspiratory flow used in a DPI?

Answer 33

Fluidise the static powder blend | De-aggregate particle agglomerates into inhalable particles

Question 34

Why is particle size problematic in DPIs? | How is this solved?

Answer 34

Particles must be small (

Question 35

Three types of DPI

Answer 35

Unit dose devices Multiple unit dose devices Reservoir devices

Question 36

Single dose inhalers DPI

Answer 36

Drug and excipients capsule inserted into device by patient Capsule broken by movement of some part of the inhaler Patients inhale the drug and excipients powder blend -not convenient to use

Question 37

Multi use dose MDI

Answer 37

Drug and excipients in blister packs Incorporates a dose counter Blister pierced by moving mechanism in the device / ratchet -relatively convenient

Question 38

Multi dose reservoir DPI (like mams)

Answer 38

Drug dispensed into the chamber by patient action eg twisting Most are disposable one use only Powder equivalent of a pMDI

Question 39

DPI advantages

Answer 39

``` Compact, portable, convenient Breath-actuated Higher doses than pMDI Dose counter Formulation easier Dry state --> better stability Environmentally friendly (no propellant) ```

Question 40

DPI disadvantages

Answer 40

``` Breath-actuated Can not be used by young children as inspiration rate too slow to trigger a DPI Different designs Affected by ambient humidity Expensive ```