PH2107 - Inhalers Flashcards
What is a DPI?
Dry Powder Inhaler
What are the features of a Pressurised Metered Dose Inhaler?
- portable
- convenient
- multidose
What are the limitations of a pMDI?
- difficult to co-ordinate
- requires propellant
- dose < 1mg per actuation
What are the opportunities for Dry Powder Inhalers?
- mostly breath-actuated (passive devices)
- propellant free
- higher doses than pMDIs
What size particles are in a DPI formulation?
Drug particles < 5um required
- BUT micronised drug particles highly cohesive
What are the problems with DPIs?
Difficult to meter and disperse powder
What interparticulate forces are found in a DPI formulation?
Van der Waals
Capillary
Electrostatic
What is a carrier blend in a DPI formulation?
- micronised drug particles
- large (lactose) carrier particles (30 - 200 um)
- drug particles easier to meter and to disperse
- drug:carrier ratios from 1:1 to > 1:100
What are the three types of DPI?
Single unit dose - gelatin - HPMC capsules Multi-unit dose from 4 to 60 doses - capsules - blisters Multidose up to 200 doses - powder reservoir
What are the two types of DPI?
Passive
Active
How does a passive DPI work?
Relies solely on the energy of the patient’s inhalation to aerosolise the powder
- patient’s inhalation disperses and delivers powder
- lung dose depends on patient’s inhalation
How does an active DPI work?
An energy source (compressed air or piezoelectric crystal) in addition to that of the patient’s inhalation is used to aerosolise the powder
What is the key factor in DPI formulations?
De-aggregation
What is ED with regards to DPIs?
Emitted dose
What is FPD with regards to DPIs?
Fine Particle Dose
What is Fine Particle Dose?
The mass of dose contained in particles with aerodynamic diameters < 5um
What is FPF with regards to DPIs?
Fine Particle Fraction
What is Fine Particle Density influenced by?
- drug and carrier particle sizes
- drug:carrier ratio
- surface roughness (rugosity)
- presence of ternary components (Fines)
Where might drug particles prefer to adhere to in a DPI?
High energy or active sites on carrier surface
What might affect influence Fine Particle Dose in DPIs?
Fine particle excipients
- may occupy active sites on carrier, so drug is more easily released
- drug and fine particle excipients may form mixed aggregates that are easily dispersed
Which fine particle excipient is usually used in DPIs?
Lactose
- magnesium sterate
- leucine
- polyethylene glycol
- mannitol
- glucose
What effect does ingress of moisture result in in a DPI?
- increased capillary force - carrier and drug particles joined by small amount of liquid which is very difficult to overcome.
- reduced particle de-aggregation
How can DPIs be protected against moisture ingress?
- individually sealed doses in blisters or capsules
- addition of moisture absorbing excipients e.g. magnesium stearate
- use of desiccant (multi-dose DPIs)
- storage of entire product in an aluminium foil pouch
What is a Spinhaler?
DPI which delivers a passive capsule unit dose
What is a Handihaler?
A newer DPI which delivers a passive capsule unit dose
What is an Aerolizer?
A newer DPI which delivers a passive capsule unit dose
What is a Dreamboat?
A DPI which delivers a passive cartridge unit dose
How does the Dreamboat inhaler work?
2 flow inlet streams converge simultaneously
- 1st stream lifts the powder from the containment region and delivers it into the 2nd inlet stream
- at the intersection, powder is broken up into particles suitable for inhalation
What is an Accuhaler?
A DPI which delivers a passive multi unit dose
What is a Turbohaler?
A DPI which delivers a passive multidose
Which conditions are variable lung doses from passive DPIs tolerated?
- asthma
- COPD
Patients take extra doses as required
Drugs have wide therapeutic windows
Why are active DPIs needed?
Drugs given for other applications (than asthma or COPD) likely to require tighter control over lung dose
- analgesics
- peptides
- proteins
- targeted therapies for local action
Active DPIs do not use patient’s inhalation to disperse powder
What is a Nektar?
An active DPI
