Aerosols Flashcards
What are the two types of aerosol systems?
Pressurised and non pressurised systems
What are aerosols?
Colloidal systems of finely subdivided liquid or solid particles dispersed in and surrounded by a gas
How is pressure applied in aerosols?
Pressure is applied through a liquefied or gaseous propellant
What are pharmaceutical aerosols primarily used for?
Pulmonary drug delivery
Consider mouth breathing, not nose breathing
What is critical about drugs in aerosol form?
The physical form of the drug.
This must be in a form of fine liquid mist or finely divided solid particles
Are aerosols administered for local or systemic effect?
Frequently used for local effect e.g. Asthma inhalers,
But have the potential to be used for systemic effect e.g. Inhaled ergotamine for migraine suffers,
Potential to administer peptide drugs like insulin
What are the primary and secondary functions of the respiratory tract?
Primary: gas exchange
Secondary: cleaning and humidifying incoming air
What is the influence of the respiratory cleaning function on drug delivery?
Incoming air is warmed and moistened. This may cause the drug to absorb the moisture and swell in size.
As particles in the respiratory tract reach their destination based on size, you may see that the drug molecule goes somewhere it is not wanted
What is the general structure of the respiratory tract?
Divided into two main portions:
Upper airways which contain the oropharynx and larynx
Lower airways which contains the bronchial tree and alveoli
What are the components of the lower airways?
Trachea, followed by successive branching.
Primary bronchus Primary bronchiole Secondary bronchiole Terminal bronchiole Respiratory bronchiole Alveolar duct Alveoli
What effect does particle size have on aerosol drugs?
Particle size is a major determinant of where the drug will deposit.
Particles <2μm deposit in the alveoli
Particles deposited in conducting airways will be trapped in mucous and swept out of the lung by ciliated epithelial cells and swallowed
Why does the particle size of water soluble materials increase in the lungs?
As they are inhaled they are moistened by the respiratory system so will absorb this excess moisture and swell
What is the pulmonary circulation?
A circulation system which is separate from the systemic circulation.
The pulmonary artery originates from the right ventricle of the heart. This divides into 2 branches for the left and right lungs.
Drugs absorbed into the pulmonary circulation are returned to the left atrium of the heart and then pumped from the left ventricle to the rest of the body
What are the implications of drug absorption into the pulmonary circulation?
This avoids the first pass hepatic effect.
Does metabolism occur in the respiratory tract?
Sometimes it may occur e.g. Fluticasone
What are the advantages of pharmaceutical aerosols?
Easy withdrawal of portions of medication without contamination or exposure to remaining material.
Aerosol container protects drug against atmospheric conditions- enhancing stability
Particle size and dose can be controlled by proper formulation and valve control
Aerosol application is clean process requiring little or no wash up by the usual
Potential for delivering peptide drugs like insulin.
Rapid onset of action and absorption
Reduced dose in comparison to other ROA for local effects and systemic effects (if drug dose is normally reduced by FPM)
Reduced systemic side effects
What are the 3 key mechanisms of aerosol kinetics which govern the majority of particle deposition within the respiratory tract?
1) impact ion
2) sedimentation
3) diffusion
What is inertial impaction?
Inertia of an airborne particle causes it to travel along its initial straight path even when the supporting airstream is suddenly deflected due to branching,
So larger particles may not be able to make the turn to deposit into its target site.
This mechanism is Important For particles >5μm and is the principle mechanism for drug deposition in nose, mouth, larynx, pharynx and large conducting airways
What is sedimentation?
Every particle falling in air accelerates to a terminal settling velocity. At this velocity, the force of gravity is balanced by the resistance of the air.
This mechanism is important for deciding the deposition of particles ranging from 0.3-3μm
How can we alter the factors to make the particle sediment faster?
Review Stokes law.
We can use this to increase particle deposition by sedimentation by:
Increase particle size to make sedimentation faster by this can cause compaction.
We can change the density of the liquid or solid.
We can alter air flow. E.g. Holding your breath for a minute slows air down to allow particles to sediment
What is diffusion?
Particle deposition by diffusion or Brownian motion predominates for very small particles of <0.5μm
This occurs predominantly in the periphery of the lung (respiratory bronchiole and alveolus) where there is minimal airflow
How do breathing patterns affect drug deposition?
Greater inhaled volume = greater peripheral distribution
Increase inhalation rate increases inertial deposition in larger airways.
Breath holding after inhalation enhances deposition by sedimentation and diffusion
What is the optimal breathing pattern?
For a patient administering an inhaler. We tell them to breathe in while simultaneously releasing the drug and then to hold their breath for 10 seconds
What are the two main components if pressurised aerosol formulations?
1) product concentrate
2) propellant
What is the product concentrate?
Contains the active drug mixed with required additives
E.g. Antioxidants, surfactants, solvents, cosolvents
May be in the form of solution, suspension or emulsion
What is the propellant?
This can be liquefied or gaseous material.
In liquefied material: e.g. Liquefied gas, it can serve as both propellant and solvent. chlorofluorocarbons used to be used but are now replaced with hydroflurocarbons due to greenhouse effects
In non liquefied material: we use compressed gases like CO2, N2 and NO
What are the advantages of N2 as a propellant?
It is insoluble in the product concentrate
It is an odourless and tasteless gas
What is the aerosol principle?
When a liquefied propellant gas is sealed within the aerosol container with product concentrate, part of the propellant changes into vapour to occupy the upper part of the container.
This forms an equilibrium between vapour and liquid phase of gas.
Vapour phase exerts a pressure in all directions against the walls of the container, the valve assembly and the surface of the liquid phase
Upon actuation of valve, the pressure forces liquid phase up through the dip tube and into atmosphere.
The propellant expands upon meeting the air and evaporates. This leaves the product concentrate as airborne droplets or dry particles
Equilibrium between vapour and liquid inside the container marinas a constant pressure after each dose
What are the components of two phased aerosol systems?
Two phased systems which contain a liquid phase and a vapour phase.
The liquid phase consists of the liquified propellant and product concentrate
The two phases are in equilibrium with each other
What are the components of 3 phased aerosol systems?
Water immiscible liquid propellant
Highly aqueous product concentrate
Vapour phase
How does the three phase aerosol system work?
The dip tube must extend only within the aqueous phase.
The liquid is forced through the dip tube by the action of pressure and sprayed by the mechanical action of the valve.
Why are three phased pressurised aerosol systems not to be shaken?
Shaking it before use can mix some of the propellant with the aqueous phase and facilitate the dispersion or foam formation after actuation
Can the propellant and liquid phases be interchanged?
Some 3 phased systems will have the propellant liquid phase at the very bottom of the container, followed by the solution liquid phase on top. In this case the dip tube should only go into solution liquid phase
Other 3 phased systems have the solution liquid phase on the bottom and the propellant liquid phase on top. In this case the dip tube goes through both liquid phases
What is the compressed gas system?
When the compressed gas is employed as a propellant .
The pressure of the gas in the head space forces the product out through the dip tube. If this gas is insoluble in the product e.g. Nitrogen, the product is emitted in the same form as it is placed
High gas pressure is required. This pressure will decrease as the product is used up
What are the benefits of using nitrogen as the compressible gas?
It is insoluble in the product and inert, thus it can protect the drug.
What are the benefits of using other gases as compressible gases?
E,g, NO, CO2. These are slightly soluble in the liquid phase and will help in the spraying process.
What are the most commonly used inhalation devices?
Metered dose inhaler - pressurised aerosol
Nebuliser - non-pressurised aerosol
Dry powdered nebuliser - non pressurised aerosol
What are the components of the metered dose inhaler?
Metal canister Gaseous propellant (head space) Actuator (plastic shell) Actuator seat Metering valve Drug solution or suspension in liquified propellant
What are examples of metered dose inhalers?
Salbutamol, sold as Ventolin, Salamol, Respigen
Combination salbutamol/ipratropium bromide sold as Combivent
What is the turbuhaler?
The dry powdered inhaler which contains 200 doses of undisputed micronised drug stored in reservoir.
Upon turning one dose is measured out and excess drug is removed by a scraper.
When inhaled, the turbulent air breaks up any aggregates and the drug is inhaled.
What is an example of a dry powered inhaler?
Budesonide, sold as the pulmicort turbuhaler
What is a nebuliser?
This allows delivery of relatively large quantities of drug during tidal breathing.
The drug is inhaled with humidified air
What is a jet nebuliser?
This uses compressed gas to convert drug solution into a spray
What is an example of a nebuliser?
Combined salbutamol/ipratropium bromide sold as Duolin
What are some examples of novel delivery devices?
The AERx pulmonary delivery system which is a type of Metered dose liquid inhaler.
Drug delivery involves extrusion of liquid through 1μm spherical holes
Can be used to deliver peptides to peripheral airways e.g. Insulin.
