Pharmaceutics - Inhalers Flashcards
What are the advantages of inhalation therapy?
Drug is delivered to the site of action
Rapid onset of action
Little drug in systemic circulation (unless done on purpose)
Very low doses needed
Explain how suspension based pMDIs are made
The drug must be insoluble in the propellant (less than 1ppm) and so freely dispersed
Must be micronized/milled beforehand
Need an adjuvant to make it physically stable (eg, SPAN 85, Oleic acid and Soya Lecithins)
At what size can particles pass through the lungs?
And why?
10 micrometers
This is because at this size the forces between each other is greater than gravity (so they become sticky)
What are the target sites, and particle size needed, for treatment of resipratory diseases and for systemic drug delivery?
Respiratory –> Bronchioles…..5 micrometers
Systemic –> Bronchioles and alveoli……2 micrometers
What are the 4 different types of DPIs?
Single Unit Dose –> Reuasble
Single Unit Dose –> Non-reuseable
Multi-unit Dose
Multi-dose Reservoir
What are the 3 main mechanisms of deposition in the lungs?
And the 2 secondary mechanisms
Intertial Impaction –> When a drug is inhaled with force is moves in a straight line until it makes contact with something (mainly large particles in the oropharynx and larynx)
Gravitational Sedimintation –> Occurs when particles velocity is low, and resident time high (in the bronchionles)
Diffusion –> When particles are bombarded by air molecules (important for terminal bronchioles and alveoli.) High residence time is best.
Interception –> Deposition where particles contact walls
Electrostatic Deposition –> Charged particles repel, causing more particles to move towards the airway walls
What is an aerosol?
And what are the 3 different types?
A relatively stable suspension of solid or liquid particles in a gaseous medium
Dust - Solid particles formed by mechanical disintigration
Smoke - A visible aerosol (due to incomplete combustion)
Fog/Mist - Liquid particles formed by condensation/atomisation
What are the 3 factors that control aerosol deposition?
Aerosol properties –> Particle size and distribution
Mode of Inhalation –> Flow rate, and breath holding Patient
Related Factors –> Obstructive airways disorders, anatomical differences
What are the 3 factors that the delivery of a respirable dose is dependent on?
Inhalation device resistance
Patient inspiratory flow
Powder formulation
Explain the differences between…
Van der Waals Forces
Electrostatic Forces
Capillary Forces
VDW –> A finite attraction between all atoms over a very small distance. These dominant at low humidity in the absense of electrostatic forces
Electrostatic Forces –> Caused by frictional contact, but over a long range. It can be either attractive or repulsive
Capillary Forces –> Condenstation of water vapour between touching molecules….forming a liquid bridge
Usually the dominant force under ambient conditions
Why can inhalation therapy be good for systemic delivery?
When the particle size is 2 micrometers, it can reach the systemic circulation
No first pass effect (Increased BA)
Extensive blood supply allows rapid absorption
Explain how solution based pMDIs are made
Always chosen if the solubility and stability of the active drug in the propellant (and co-solvents) are good
Usually need to add co-solvents, like ethanol, to increase solubility, as the amount of drug released with each inhalation is dependent on its solubility
HCl often used to modify the pH of the drug
Explain how a pMDI works
Delieved as a metered liquid volume, and inhaled upside down
Made at 4 bar (high) pressure, which is maintained by the metering valve…keeping the pressure in the main compartment at all times. Also done by the liquid-vapour equilibrium
The atomising nozzle boils the gas, producing single droplets
These droplets are then cooled and condensed outside of the inhaler (forming the spray we see)
What are the main benefits from using a spacer with a pMDI?
Causes the aeresol to slow down
Smaller particles are formed (from the aeresol) as the larger particles contact against the spacer –> these points cause the drug to have less momentum….allowing them to get deeper into the lung
Enables the patient to use tidal breathing
What are some of the problems with solution based pMDIs?
Polar co-solvents can can cause errosion of aluminium canisters….so plastic coats are needed
The relatively non-volatile co-solevent lowers the internal propellant pressure….and so atomisation is less effective
Of all the problems with pMDIs….which is the greatest problem (statistically) for patients?
A slow inhalation (30L/min)
What type of bond formation is the base of Carrier based systems, and Agglomerated systems?
Carrier Based –> Adhesive bonds
Agglomerated –> Cohesive bonds
What are Carrier-based formulaitons?
The blending of the drug with a carrier (eg, lactose)
Allows the accurate metering of small quantities of drug
Improves handling and processing
Particle size distribution/habit (shape) and surface morphology are all important properties that are used to influence Fine Particle Fraction (FPF)
What are Agglomerated Powder Systems?
For high dose drugs, when carrier-based formulations are not feasible
Produced via cohesive bond formation
Efficient deaggregation is required to allow the particles to get deep into the lungs as discrete particles
Have a high free surface area and energy drug
Do DPIs have propellants?
No they don’t
What is a Nebuliser?
A drug contained within a sterile solution
What’s a Pneumatic Nebuliser?
The dominant one pre-2000
Has 2 nozzles
Contains a inertial filter to trap large particles
They are cheap
What is a High Frequency Ultrasonic Nebuliser?
Electronically powered
Has a fan to drive the aerosol from the device
Aerosol droplet either occurs via Taylor Instability or Cavitation
Produce reproducible results
High Output
Lower aerosol inertia
What is the goal of new/recent nebulisers?
Enhance output
Shorten nebulisation time
