Pulmonary Drug Delivery I Flashcards
Why drugs are delivered by respiratory route
- Rapid onset activity and local effect (brochodialators salbutamol)
- Smaller dose needed more economical
- High bioavailability as high first pass met
- High lung surface area and good blood supply systemic delivery
Pulmonary drug delivery
- Drug physicochemical
properties - Formulation
- Patient
- Delivery system
Importance of particle size
- Solid particles suspeneded in air or liquid in air
- Gas administer via pulmonary route oxygen or anesthetic
Measuring partical size
- Physical diameter = Particle density/ unit density
Aerodynamic diameter
- The diameter of a sphere of which settles through air with a velocity equal to that of the particle in question
Limitations of repiratory route
- Evolved to inhale specific gases and not forigen particles
Inertial impaction
- Occours in upper airways and velocity and mass of particles cause impact on airways surface
Impaction dependant on
- Particles momentum
- Position of particles in airstream
- Angle of bifucation
- 10 micrograms 50% deposition
Sedimentation
- Suspened in gas subject to vertical gravitational force
- Mechanism of depositing in lower airways
- Sedimentation less relevet when particle size decrease
Diffusion
- Particles <0.5 microgram
- ## Smaller particles more deposition in peripheral lung and alveolar space
Minor mechanism of deposition
- Inception of elongated particles
- Charge reflection of charged particles
Structure of airways
- Up to 6x10^8 alveoli in lungs
Drug Delivery Devices
– Pressurised metered-dose inhalers
– Dry powder inhalers
– Nebulisers
– Electronic cigarettes
Pressurised metered-dose inhalers
- Delivery of adrenaline or isoprenaline (medihaler)
- β2-receptor agonist
salbutamol - Dispersed in the liquid propellant via solution or suspension
- Actuation of a metering valve
Pressurised metered-dose inhalers
- Canister that is aluminium
- Metering valve control volume delivered
- Propellant: hydrofluoroalkanes HFA-134a and HFA-227
State of propellents used inhalers
- Liquified gases as pressure causes conversion of liquid in canister to gas when actuated
Filling of pMDI canisters: Cold filling
- Drug, excipient and propellent chilled - 60 degrees
- Further chilled and added to canister sealed with valve
- Leak tested placed in water bath and weighed
Pressure filling
- Ethanol can be used before valve crimped in place
- Drug + excipients + propellant
added to canister under
pressure - Further propellent added under pressure
- Leak tested in water bath and weighed
Formulation of pMDIs: Greenhouse gas
- chlorofluorocarbons contain in original pMDIs but damage to ozone layer
- Replace with hydrofluoroalkanes
- Still geenhouse gas must be phased out
Formulation of pMDIs: Use of surfactant
- Dispersed in the propellant as a solution/ suspension
- HFA-134a and HFA-227 exhibit low relative permittivity values so are not good solvents
- Surfactants may be required as suspending agents E.G. Lecithin, Oleic acid, Sorbitan trioleate
Co-solvents used in pMDIs
Ethanol, 2-propanol, can be added to aid solubility of drugs and excipients
beclometasone pMDIs
- Dissolved in the propellant this can lead to very small particles (more potent)
Sustainability of pMDIs
- Bulky dosage forms use plastic and aluminium
- Can be recyclable but no national recycling scheme exist
Ventolin vs Salamol
- Ventolin high carbon footprint
- Salamol lower carbon footprint and high global warming potential
Advantages of pMDIs
- Portable
- Low cost
- Drug protected in canister
- Multipe dose in one device
- Reproduceable dose Efficient at drug delivery
- Disposable
Disadvantages pMDIs
- Incorrectly used by patient
- Greenhouse gases
