P2: PMDI Formulations

Question 1

what does PMDI stand for

Answer 1

pressurised metered dose inhaler

Question 2

what are PMDIs

Answer 2

compact pressurised aerosol dispensers

Question 3

what is the API dose range in PMDIs

Answer 3

25 micrograms to 5mg

Question 4

what are the components of a basic MDI

Answer 4

aerosol canister, drug/propellant formulation, metering valve, atomising nozzel
releasing an aerosol cloud of aerosol droplets

Question 5

how are metering valves operated at rest

Answer 5

metering valve is closed

Question 6

how are metering valves operated at the start of actuation

Answer 6

metering valve closed at both points

Question 7

how are metering valves operated at dose release

Answer 7

between drug and opening is closed; metering valve is opening

Question 8

how is spray formed in a pMDI

Answer 8

1. shearing forces produce ligaments
2. propellants start to boil in expansion chamber
3. patient presses can which opens the channel between metering chamber and atmosphere
4. propellant droplets form at actuator nozzel “2 phase gas-liquid air blast”
5. initial velocity 30m/s; initial droplet side 20-30micrometers
6. evaporation and cooling

Question 9

what are the three different drug formulations for pMDIs

Answer 9

suspension technology, solution technology, non-volatile solution technology

Question 10

why is suspension technology used in pMDIs

Answer 10

drug and crystal propellant; leading to distribution of milled drug

Question 11

why is solution technology used in pMDIs

Answer 11

solubility of drug

Question 12

why is non-volatile solution technology used in pMDIs

Answer 12

aerosol droplets; non volatile additives

Question 13

what are suspension based formulas used in pMDIs

Answer 13

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

Question 14

what is rapid flocculation

Answer 14

loose agglomerates (interparticulate forces)
form of physical instability

Question 15

what is bulk separation

Answer 15

creaming or sedimentation (density, particle size)

form of physical instability

Question 16

what is irreversible aggregation

Answer 16

Ostwald ripening, crystal growth and caking (solubility)

form of physical instability

Question 17

what is crystal structure instability

Answer 17

polymorphic interconversion

form of physical instability

Question 18

what is the role of excipients

Answer 18

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

Question 19

what are common surfactants used in pMDIs

Answer 19

sorbitan trioleate
oleic acid
soya lecithins

Question 20

why would a co-solvent be used in a pMDI

Answer 20

to stop freely soluble drugs crystallising out during shelf-life
amount of emitted dose directly related to solubility

Question 21

what are some problems associated with solution based inhalers

Answer 21

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

Question 22

how does liquefied propellant work

Answer 22

activation -> vapour loss -> pressure drop -> liquid vapourisation and pressure restored -> activation
cycle continues

Question 23

what are the types of liquid propellant

Answer 23

hydrocarbond - flammable
CFCs - phased out
HFAs - CFC replacement

Question 24

what is a HFA

Answer 24

hydrofluoroalkanes

CFC replacement

Question 25

what does CFC stand for

Answer 25

chlorofluorocarbon

Question 26

what are the reformulation issues with HFAs

Answer 26

conventional surfactants are insoluble in HFAs

HFAs affect conventional valve elastomers so acuator design is more critical

Question 27

what are the advantages of pMDIs

Answer 27

many doses, compact, consistent delivery, relatively cheap, sealed canister protects drug, lower capital costs for market entry

Question 28

what are the disadvantages of pMDIs

Answer 28

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

Question 29

what are the instructions for pMDI use

Answer 29

1. 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

Question 30

what are the solutions to incorrect inhaler use

Answer 30

using spacers or breath actuated inhalers