Inhalers and deposition Flashcards
What is an Aerosol?
A relatively stable suspension of solid/liquid particles in a gaseous medium (0.001mcm-100mcm)
Aerosol behaviour is affected by…
Interaction with surrounding air molecules and gravity
It’s own size, shape and density
The target site of aerosolised drugs is …
Respiratory bronchioles and alveoli
The pattern of deposition in the lungs…
The larger the particle the further up the airways it is deposited with any particle >10mcm getting trapped in the back of the throat
Advantages of inhaled drugs (local delivery)
- Drugs delivered directly to site of action
- The onset of action is rapid
- Less drug gets into systemic circulation (For local delivery)
- Less of the drug is necessary for a therapeutic effect
Advantages of inhaled drugs (systemic delivery)
- Extensive blood supply allows for rapid absorption into systemic circulation
- Avoids 1st pass metabolism
- Therefore increased availability
Factors controlling deposition
Aerosol properties- size and distribution
Mode of inhalation- volume inhaled, flow rate and breath holding pause
Patient factors- anatomy/physiology differences, respiratory disease
But primarily affected by size and flow rate
Primary deposition mechanisms in the lung
Inertial impact (90%)- kinda just smacks into epithelium because they’re moving in a straight line. Mostly large particles
Sedimentation (9%)- the particle moves along slowly, loses energy and plops down. Important for depositing in bronchi
Diffusion (1%)- Particle happily floats along an settles down at a dead end, Earns lots of frequent flyer points. Important for deposition in bronchi/alveoli
The smaller the diameter the further along the resp. tract it gets. Small bois fly far.
Oropharynx>bronchi>alveoli
Secondary deposition mechanisms
Interception- where particles contact walls (especially fibres at airway bifurcations
Electrostatic deposition- charged particles can repel each other towards walls
5 essential components of a MDI
Drug Propellent Aerosol canister Metering valve Atomising nozzle
Suspension based formulation
Suspensions preferred due to chemical stability and is capable of delivering high powder loads
Drug must be milled to respirable size <5mcm and must be insoluble
Shaking required to redisperse drug to ensure suspension is homogenous
Role of adjuvant
To ensure physical stability of suspension
Must be capable of dispersing and redispersing the drug
Minimise segregation before administration of the drug
Common surfactants
SPAN 85, oleic acid and soya lecithins in CFC’s
Oleic acid, magnesium stearate, PEG/PVP in HFA’s
Solution based formulations
Suitable if solubility/stability is adequate
Amount of emitted dose is directly related to solubility therefore usually requires a cosolvents as propellants are usually poor solvents
Potential for drugs to recrystallise due to changing temperatures
Problems of solution based formulations
Polar co solvent can cause corrosion of Al cannister
Co solvent lowers internal propellant pressure therefore atomisation less effective
Modifying drug to be more soluble is most effective solution
Liquid propellant
Good because no loss of pressure after actuations
This because the loss in pressure causes vapourisation of the propellant which restores the pressure within the cannister
Advantages of pMDI’s
Consistent dose
Cheap
Resistant to moisture
Compact
Disadvantages
Patient coordination required
Cold freon effect results in inconsistent delivery
Tail off at the end of a can
High deposition in throat
Very little intellectual property protection for pharm R and D
DPI’s (Dry powder inhalers)
Driven by patient inspiration
Easy to use Patient/environment friendly
Long term replacement for pMDI’s
DPI mechanism of action
Inspiration creates energy for fluidisation and entrainment of formulation
Energy caused by pressure drop (deltaP) that s due to inhalation flow (Q) and internal resistance of device (R)
A minimum inhalation flow must be created (Qmin) before dose can be released
Relationship between device and airflow
R effects speed/acceleration of airflow through the device
Acceleration effects DPI efficacy
Speed affects the amount deposited in the lungs
Factors affecting respirable dose
R, Q and the powder formulation
Particle interactions are dictated by…
Van der waals forces
Electrostatic forces
Capillary forces
Contribution of each of these depends on interacting materials and humidity
Van der waals forces
Dominant at short range in low humidity where there is no electrostatic forces
Capillary forces
Water condenses between to particles and forms a liquid bridge
Force directly related to humidity and hydrophobicity
Dominant at ambient conditions
Electrostatic forces
Due to friction between different materials
Long range force
Can be attractive or repulsive and increase at low humidity
3 interactions that must be controlled
Drug-drug (Cohesion)
Drug-excipient (Adhesion)
Drug-device (Segregation)
2 formulation strategies
Carrier based- uses adhesion to bind drug to a carrier
Agglomerated- uses cohesion to form an agglomerate which is broken up during inspiration
Advantages of carrier based formulations
Accurate dosing of small quantities of a potent drug
Improved handling and processing
Carrier size, shape and morphology can be changed to influence fine particle friction (FPF)
Advantages of agglomerated powder systems
More suitable for high dose drugs
However efficient deaggregation of agglomerate must occur so that drug is presented as discrete particles in the lung
Advantages of DPI’s
Propellant free No or very little excipients Large doses can delivered In dry form Breath actuated
Disadvantages of DPI’s
Dependant on patients inspiration force
Due to higher velocity there is increased chance of inertial impaction
Exposure to ambient conditions can reduce stability
Less efficient at delivery than a pMDI
Nebulisers
A drug contained within a sterile solution
Significant variation occurs a lot drug being left within the device, in expiration and many particles are to small or large
As little as 10% of the target dose maybe delivered
Pneumatic nebuliser
Works by using a high velocity air jet to blow air very quickly causing them to break into small particles
A baffle (inertial filter) traps oversized particles
Pneumatic nebuliser pros and cons
Cheap and can achieve small particle sizes
But: has variable performance
Dead (stagnant) volume
Lower output
Not very portable
Ultrasonic nebulisers
Uses a piezoelectric ceramic disc which oscillates and causes droplet production
Ultrasonic nebuliser pros and cons
Consistent
Produces small particles
High output
Small and quiet
But: low inertia particle size increases at end of life expensive heats solution to 40 degrees celsius Unsuitable for suspensions
Soft mist inhalers (SMI’s) and Liquid dose inhalers (LDI’s)
Based on a drug dissolved in non volatile liquid
Volumetric dosing
Breath actuated
Dose emitted as a slow moving cloud
AERx LDI
A hand held nebuliser
Uses an actuater to extrude drug, held in 50mcl through tiny micron sized holes
Microelectronics guide patient for optimum inspiration
Respimat mechanism
Drug stored in solution
Solution is forced through micro nozzle as patient inhales
Respimat advantages
Avoids moisture problems and powder aggregation that can occur with DPI’s
Can deliver a metered dose
