P2: PMDI Formulations Flashcards
what does PMDI stand for
pressurised metered dose inhaler
what are PMDIs
compact pressurised aerosol dispensers
what is the API dose range in PMDIs
25 micrograms to 5mg
what are the components of a basic MDI
aerosol canister, drug/propellant formulation, metering valve, atomising nozzel
releasing an aerosol cloud of aerosol droplets
how are metering valves operated at rest
metering valve is closed
how are metering valves operated at the start of actuation
metering valve closed at both points
how are metering valves operated at dose release
between drug and opening is closed; metering valve is opening
how is spray formed in a pMDI
- shearing forces produce ligaments
- propellants start to boil in expansion chamber
- patient presses can which opens the channel between metering chamber and atmosphere
- propellant droplets form at actuator nozzel “2 phase gas-liquid air blast”
- initial velocity 30m/s; initial droplet side 20-30micrometers
- evaporation and cooling
what are the three different drug formulations for pMDIs
suspension technology, solution technology, non-volatile solution technology
why is suspension technology used in pMDIs
drug and crystal propellant; leading to distribution of milled drug
why is solution technology used in pMDIs
solubility of drug
why is non-volatile solution technology used in pMDIs
aerosol droplets; non volatile additives
what are suspension based formulas used in pMDIs
can deliver high power loads; required the drug to be milled or micronised
required the drug to be practically insoluble in the propellant and freely dispersed
requires re-dispersion and formulation homogenicity by shaking
what is rapid flocculation
loose agglomerates (interparticulate forces) form of physical instability
what is bulk separation
creaming or sedimentation (density, particle size)
form of physical instability
what is irreversible aggregation
Ostwald ripening, crystal growth and caking (solubility)
form of physical instability
what is crystal structure instability
polymorphic interconversion
form of physical instability
what is the role of excipients
to ensure physical stability of suspension
must be capable of dispersing and re-dispersing the drug in suspension
allows homogenous distribution of the drug within the suspension
minimal segregation during the period prior to administration
what are common surfactants used in pMDIs
sorbitan trioleate
oleic acid
soya lecithins
why would a co-solvent be used in a pMDI
to stop freely soluble drugs crystallising out during shelf-life
amount of emitted dose directly related to solubility
what are some problems associated with solution based inhalers
co-solvents can cause corrosion of aluminium canister
drugs can be relatively unstable
co-solvent lowers the internal propellant pressure, so atomisation is less effective
how does liquefied propellant work
activation -> vapour loss -> pressure drop -> liquid vapourisation and pressure restored -> activation
cycle continues
what are the types of liquid propellant
hydrocarbond - flammable
CFCs - phased out
HFAs - CFC replacement
what is a HFA
hydrofluoroalkanes
CFC replacement
what does CFC stand for
chlorofluorocarbon
what are the reformulation issues with HFAs
conventional surfactants are insoluble in HFAs
HFAs affect conventional valve elastomers so acuator design is more critical
what are the advantages of pMDIs
many doses, compact, consistent delivery, relatively cheap, sealed canister protects drug, lower capital costs for market entry
what are the disadvantages of pMDIs
patient co-ordination and force required to actuate, tail off at the end of a can, force of aerosol spray, varying deposition pattern in airways, minimum IP protection in R&D
what are the instructions for pMDI use
- shaken before use 2. pt inhales slowly while simultaneously activating the canister 3. continue to inhale slowly through actuation 4. upon actuation the inspirational breath should be held
what are the solutions to incorrect inhaler use
using spacers or breath actuated inhalers
