Aerosols - Delivery Systems And Formulation For Inhalation 2 Flashcards
What is an aerosol?
Dispersion of solid particles or liquid droplets in a gas
What three times of inhalers are there?
Nebulisers
Pressurised metered dose inhalers
Dry powder inhalers
Which is the most widely used inhaler and why?
PMDI - most convenient
What is a nebuliser?
Aqueous drug solution / suspension aerolised into droplets - energy provided by compressed air or ultrasound
What is a pMDI?
How is compliance improved by pMDI?
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
What is a DPI?
Dry powder inhaler
Drugs normally with other solid excipients in dry powder state
Aerosolisation by patient
What are the two types of nebuliser?
Jet Nebuliser (or atomiser) Ultrasonic Nebuliser
How does a Jet Nebuliser work?
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
How does an Ultrasonic Nebuliser work?
Piezoelectric crystal emits high frequency signal
Breaks drug solution / suspension into droplets for inhalation
Lighter and quieter than a jet nebuliser
What is a drawback of Ultrasound Nebuliser?
Some drugs are degraded by the ultrasound
How is a nebuliser used?
Patient breathes normally into the face mask or mouth piece
Advantages of a nebuliser
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
Disadvantages of nebulisers
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
Criteria for a pMDI container
Withstand high pressure Robust Light in weight Inert Made of aluminium or stainless steel (steel better for higher pressures)
What is a pMDI metering valve?
Ensures accurate and reproducible volume of drug formulation is delivered
Delivered from continuous spray valves
20-100 microlitres
Properties of a pMDI propellant ?
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
Discuss CFC propellant
Ozone depleting
Banned
Responsible for the cold - freon effect
Discuss hydrofluoroalkanes as propellant
Drugs needed to be reforms later due to different properties of HFA compared to CFC
New valve materials developed
If a drug is soluble in propellant how is it formulated into a pMDI?
Solubilised in propellant
Ethanol might be added as a co-solvent
If a drug is insoluble in propellant how is it formulated into a pMDI?
Micronised drug particles are suspended in propellant
Surfactants added to increase suspension stability
Most common pMDI formulation
What is needed to form an aerosol?
Source of energy
What is the main concern for each dose from a pMDI?
Each dose is correct and the volume of suspension is homogenous
Why are surfactants added to the formulation of a pMDI?
Improve stability / homogeneity of the suspension
Aid the formulation of a flocculated suspension (easily redispersible)
What are the four main problems facing the suspension in a pMDI inhaler?
Sedimentation (non-homogeneity)
Flocculation (reversible aggregation)
Caking - difficult to redisperse
Particle size growth by Otswald ripening (deposition in the lungs reduced)
What are the ideal criteria for suspension of pMDI?
Slow flocculation
Slow sedimentation
Easy redisperse
I.e partially flocculated suspension
What other add on excipients can be used in pMDI?
Flavours Sweeteners Lubricants Density modifiers Antioxidants
How do spacer devices help with inhalation of pMDI?
Increase lung deposition
- delay between actuation and inhalation
- decrease the velocity of the spray
- more time for propellant to evaporate
Why is the dose inhaled by a patient reduced when using a spacer and pMDI?
Deposition in the device due to electrostatic charges causing droplets to stick to the chamber
pMDI advantages
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
pMDI disadvantages
Usually no breathe actuation
Low lung deposition
No dose counter (to record used)
Only low doses can be delivered (
What is a Dry a Powder Inhaler?
Dry powder, no solvent is involved
Main components of a DPI
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
How is patients inspiratory flow used in a DPI?
Fluidise the static powder blend
De-aggregate particle agglomerates into inhalable particles
Why is particle size problematic in DPIs?
How is this solved?
Particles must be small (
Three types of DPI
Unit dose devices
Multiple unit dose devices
Reservoir devices
Single dose inhalers DPI
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
Multi use dose MDI
Drug and excipients in blister packs
Incorporates a dose counter
Blister pierced by moving mechanism in the device / ratchet
-relatively convenient
Multi dose reservoir DPI (like mams)
Drug dispensed into the chamber by patient action eg twisting
Most are disposable one use only
Powder equivalent of a pMDI
DPI advantages
Compact, portable, convenient Breath-actuated Higher doses than pMDI Dose counter Formulation easier Dry state --> better stability Environmentally friendly (no propellant)
DPI disadvantages
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
