Low boiling point required to give you smaller

Low boiling point required to give you smaller particles by vaporizing more quickly
Parts – canister, metering chamber/valve, actuator
May use a spacer (not in DPI)
 Advantages – reduced hand-breath-eye coordination, reduces local & systemic AEs, large drug doses more conveniently
delivered (spread out more and better absorbed)

 Disadvantages – bulkier & less portable, more expensive than MDI alone, require cleaning to reduce electrostatic charge,
optimal inhalation technique unknown, not suitable for all MDI canisters
Formulation considerations:
 Propellant have high vapor pressure at room temperature
o The rapid reduction in pressure from the sealed chamber to atmospheric pressure induces extremely rapid
evaporation and the latent heat of evaporation of the volatile propellants provides the energy for atomization
 The higher the vapor pressure of the propellant (low BP), the smaller the particle size of the droplets
 Cosolvents are present for the solubilization of surfactants and to facilitate flocculation of the suspension
o Help facilitate delivery of consistent doses
o Deflocculation is desirable for MDI – smaller particles
 Surfactants provide wetting of insoluble drugs
Dry Powder Inhalers
Breath-actuated and require an adequate inspiratory flow-rate for drug delivery
 No propellants
 Not usually appropriate for acute asthma attacks
Small therapeutic doses
Formulation considerations:
 Diameter should be 1-3 microns
 Lactose monohydrate is commonly used as a filler to improve filling and reduce particle aggregation and flow of the drug
o Unoptimized powder blends can exhibit aggregation
o Forms loose covalent bonds that are disturbed when inspiratory force is pushed upon them
 ProAir Respiclick is the only FDA indicated DPI rescue inhaler
Nebulizers
Convert aqueous solutions or micronized suspensions into aerosol for inhalation
Atomization causes large increase in surface area and transportation of droplets by the external energy input
Forces responsible: surface tent, viscosity, and extent of aerodynamic force
 Low surface tension ensures breaking of air-liquid interface
 High viscosity resists breakdown of particles
 High aerodynamic force helps break the interface
Venturi/Air-jet Nebulizer – drug drawn up the capillary and high shear converts the liquid to polydispersed aerosol
 Larger drops are removed by baffles
 Causes cooling of solution and with vapor loss, this increases the concentration of the drug with time
o Could cause recrystallization
 Distinct advantage in young children
Ultrasonic nebulizers – produce high frequency sound waves using a piezoelectric transducer that increase solution temperature and
produce droplets with high aerodynamic diameter
Formulation considerations:
 Solution has to be sterile and above pH 5
 Cosolvents can improve drug solubility but could increase viscosity (and therefore particle size)
o Do not use suspension (cannot be vaporized)
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