pMDI's Flashcards
What is a pMDI?
Pressurised Metered Dose Inhaler
- drug is dissolved/ suspended in a liquid propellant together with other excipients (surfactants) and presented in a pressurised cannister fitted with a metering valve.
- a pre-determined dose is released as a spray on actuation of the metering valve
- upon release, formulation undergoes volume expansion in the passage within the valve and forms a mixture of gas and liquid before discharge from the orfice
- high speed gas flow helps to break up the liquid into a fine spray of droplets
Types of materials aerosols may be packaged into.
- tin-plated steel
- plastic-coated glass
- aluminium
note that glass could slip from hands during an asthma attack
What material do pMDI’s use and why?
Aluminium produced by extrusion to give seamless containers with a capacity of 10-30mL
Is strong and inert- protects high pressure of liquid formulation
Can be used uncoated when there is no chemical instability between container and contents.
Can have an internal coating of a chemically resistant organic material such as epoxy resin, PTFE
What are the requirements for all inhalers?
- generate and aerosol of reproducible aerodynamic size and size distribution
- deliver a therapeutically relevant dose of drug
- be easy to use for patients
Name the components of pMDI
- aerosol cannister
- headspace
- inhaled air entry
- drug suspension
- rib to hold cannister in place
- crimp (cannister seal)
- gasket
- metering valve
- mouthpiece
- actuator body
- atomising nozzle
- valve stem
What is the purpose of the crimp?
Cannister seal
- made of different materials
- does not allow the propellant to escape
- improper seal causes a higher dose of drug inside
^ which can cause side effects or will block the cannister
How does the metering valve work?
- depression of valve stem allows the contents of the metering chamber to be discharged through the orifice i in the valve stem and made available to the patient
- after actuation, the metering chamber refills with liquid from the bulk and is ready to dispense the next dose
- pMDI needs to be primed prior to first use so the metering chamber is fully filled
(press into air not into mouth on first dose)
‘permits the reproducible delivery of small volumes of product’
ensure valve is closed properly as the smallest amount of oxygen could change the drug deposition.
Why must the cannister be strong?
Upon activation, drug is released and propellant operates very fast.
Atmospheric pressure is 1 bar, pressure in cannister is 4-5 bars.
Canister must be very strong so if dropped, it won’t explode.
What are the two hypotheses for atomisation?
Internal flash evaporation - big propellant droplet at start of release - contact of pressure with atmosphere - release of small particles into lungs (no propellant)
Aerodynamic breakup
- propellant divides into smaller molecules
What are propellants?
At room temp, pressure they are gases but are readily liquefied by decreasing temperature or increasing the pressure.
Are liquefied gases, traditionally CFC’s & HFA’s
Which propellants are used in pMDI’s?
HFA134a
Higher BP, pressure, water solubiltity, lower log P
Has 2 hydrogens in its structure- allows for more hydorgen bonding- more soluble
HFA227
Poorer solubility due to one hydrogen
Both are non-flammable, non -toxic, do not deplete the ozone layer.
But have low aqueous solubility and lipid solubility so are difficult to formulate.
What are the environmental problems of HFA’s?
Although they are non-depleting gases, they contribute to global warming.
Kyoto Protocol
- control of production for the use of non- essential items (inhalers are essential)
- No ban on use of HFA in essentials such as MDI till an alternative substance is available to use.
Technical problems of HFA’s
Suspension stability
- In HFA driven pMDI’s, most surfactants are insoluble in HFA and need a co-solvent in HFA such as alcohol.
- This changes the taste and is a problem for certain individuals. Must tell patient that it contains alcohol even though it is a very low concentration.
Valve material incompatibility
- Valves in MDI are made up of different materials such as metal, rubber and plastic.
- these materials may react with the co-solvent used in HFA pMDIs leading to impaired valve performance
Moisture
- HFA have relatively high affinity to moisture
- this is increased by use of alcohol has a co-solvent
- leads to increased chemical instability during storage and decreased bioavailability of drugs due to deposition on walls of apparatus
What properties must the drug particles have in a pMDI formulation?
Drug particles must be micronised.
Done in a fluid energy mill with a target size of 1-5 microns.
Careful monitoring of solid state properties.
What can the drug be formulated as in aerosols?
Either solutions or suspensions of drug in the liquefied propellant.
