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Pharm303 > Aerosols > Flashcards

Aerosols Flashcards

0
Q

What are the two types of aerosol systems?

A

Pressurised and non pressurised systems

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1
Q

What are aerosols?

A

Colloidal systems of finely subdivided liquid or solid particles dispersed in and surrounded by a gas

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2
Q

How is pressure applied in aerosols?

A

Pressure is applied through a liquefied or gaseous propellant

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3
Q

What are pharmaceutical aerosols primarily used for?

A

Pulmonary drug delivery

Consider mouth breathing, not nose breathing

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4
Q

What is critical about drugs in aerosol form?

A

The physical form of the drug.

This must be in a form of fine liquid mist or finely divided solid particles

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5
Q

Are aerosols administered for local or systemic effect?

A

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

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6
Q

What are the primary and secondary functions of the respiratory tract?

A

Primary: gas exchange
Secondary: cleaning and humidifying incoming air

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7
Q

What is the influence of the respiratory cleaning function on drug delivery?

A

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

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8
Q

What is the general structure of the respiratory tract?

A

Divided into two main portions:
Upper airways which contain the oropharynx and larynx
Lower airways which contains the bronchial tree and alveoli

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9
Q

What are the components of the lower airways?

A

Trachea, followed by successive branching.

Primary bronchus
Primary bronchiole
Secondary bronchiole
Terminal bronchiole
Respiratory bronchiole
Alveolar duct
Alveoli
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10
Q

What effect does particle size have on aerosol drugs?

A

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

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11
Q

Why does the particle size of water soluble materials increase in the lungs?

A

As they are inhaled they are moistened by the respiratory system so will absorb this excess moisture and swell

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12
Q

What is the pulmonary circulation?

A

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

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13
Q

What are the implications of drug absorption into the pulmonary circulation?

A

This avoids the first pass hepatic effect.

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14
Q

Does metabolism occur in the respiratory tract?

A

Sometimes it may occur e.g. Fluticasone

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15
Q

What are the advantages of pharmaceutical aerosols?

A

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

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16
Q

What are the 3 key mechanisms of aerosol kinetics which govern the majority of particle deposition within the respiratory tract?

A

1) impact ion
2) sedimentation
3) diffusion

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17
Q

What is inertial impaction?

A

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

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18
Q

What is sedimentation?

A

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

19
Q

How can we alter the factors to make the particle sediment faster?

A

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

20
Q

What is diffusion?

A

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

21
Q

How do breathing patterns affect drug deposition?

A

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

22
Q

What is the optimal breathing pattern?

A

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

23
Q

What are the two main components if pressurised aerosol formulations?

A

1) product concentrate

2) propellant

24
Q

What is the product concentrate?

A

Contains the active drug mixed with required additives
E.g. Antioxidants, surfactants, solvents, cosolvents

May be in the form of solution, suspension or emulsion

25
Q

What is the propellant?

A

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

26
Q

What are the advantages of N2 as a propellant?

A

It is insoluble in the product concentrate

It is an odourless and tasteless gas

27
Q

What is the aerosol principle?

A

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

28
Q

What are the components of two phased aerosol systems?

A

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

29
Q

What are the components of 3 phased aerosol systems?

A

Water immiscible liquid propellant
Highly aqueous product concentrate
Vapour phase

30
Q

How does the three phase aerosol system work?

A

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.

31
Q

Why are three phased pressurised aerosol systems not to be shaken?

A

Shaking it before use can mix some of the propellant with the aqueous phase and facilitate the dispersion or foam formation after actuation

32
Q

Can the propellant and liquid phases be interchanged?

A

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

33
Q

What is the compressed gas system?

A

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

34
Q

What are the benefits of using nitrogen as the compressible gas?

A

It is insoluble in the product and inert, thus it can protect the drug.

35
Q

What are the benefits of using other gases as compressible gases?

A

E,g, NO, CO2. These are slightly soluble in the liquid phase and will help in the spraying process.

36
Q

What are the most commonly used inhalation devices?

A

Metered dose inhaler - pressurised aerosol
Nebuliser - non-pressurised aerosol
Dry powdered nebuliser - non pressurised aerosol

37
Q

What are the components of the metered dose inhaler?

A 
Metal canister 
Gaseous propellant (head space)
Actuator (plastic shell)
Actuator seat 
Metering valve
Drug solution or suspension in liquified propellant
38
Q

What are examples of metered dose inhalers?

A

Salbutamol, sold as Ventolin, Salamol, Respigen

Combination salbutamol/ipratropium bromide sold as Combivent

39
Q

What is the turbuhaler?

A

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.

40
Q

What is an example of a dry powered inhaler?

A

Budesonide, sold as the pulmicort turbuhaler

41
Q

What is a nebuliser?

A

This allows delivery of relatively large quantities of drug during tidal breathing.
The drug is inhaled with humidified air

42
Q

What is a jet nebuliser?

A

This uses compressed gas to convert drug solution into a spray

43
Q

What is an example of a nebuliser?

A

Combined salbutamol/ipratropium bromide sold as Duolin

44
Q

What are some examples of novel delivery devices?

A

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.

Pharm303 (15 decks)

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