Pulmonary Drug Delivery

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What is an aerosol? (1)
A suspension of small solid particles or droplets suspended in a gas or vapour. Only delivery through the mouth is considered an aerosol.
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What are the functions of the respiratory tract?
1) Gas Exchange 2) Cleaning and humidifying of incoming air to prevent lung damage
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How are large molecules caught in the lung? (1)
Impaction
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What is inhaled particle deposition dependant on? (6)
Particle size. 5-2 microns. Bronchi and bronchioles. Sedementation.
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What are the exceptions? (2)
Large needle shaped particles (not often used as difficult to formulate)
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Uses of Pharmaceutical Aerosols? (6)
LA- bronchodilators, antiinflammatory steroids, anti allergics, antivirals. Systemic - smoking cessation and migraine relief
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What maybe future aerosol formulations? (7)
Proteins and peptides, anti-infectives, pain management, Vaccines, Hormones, gene therapy and immunoglobulins.
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3 current pulmonary delivery devices? (3)
Pressured sprays, Nebulisers, Dry Powders
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What are the components of a pMDI? (6)
Canister, Metering Valve, Actuator, Actuator Seat, Propellant/Excipient Mix, Drug Sol.
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What does the solution contain? (4)
Active Ing. Propellant, Surfactant, Excipients
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what does the propellant provide? (2)
Driving force to expel the product, also acts as a dispersion medium
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Discuss propellants. (5)
Traditionally CFC's. Now HFA's due to environmental risk. Gas at room temp. Formulation under low temp high pressure (liquid), liquid in canister due to high pressure of container.
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which CFC's are still used? (3)
CFC 11, CFC 12, CFC 114
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What is intermediate pressure of propellants? (2)
Suitable blends give an intermediate vapour pressure, usually about 450kPa. Given by Raoults Law
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State Raoult's Law.
The vapour pressure of a mixed system is equal to the sum of the mole fraction of each component multiplied by its vapour pressure
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A proper blend of propellants allows for.... (10)
Manipulation and control of: Vapour pressure (fine particle fraction, leakage, choice of filling) Liquid density (reproducible doses) and Solvency (insol or sol okay - partial is an issue)
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Discuss VP and BP of HFA's. (2)
VP of HFA's is likely to be high unless a low volatility component, such as ethanol, is included in the MDI formulation. propellant BP impacts method of filling
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Discuss solvency of HFAs? (6)
partial solubility - may result in crystal growth giving poor physical stability and unacceptable performance. Surfactant solubility is v much reduced with HFAs - dec phys stability and function of elastometic components influenced.
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How does crystal growth occur and what does it cause? (3)
Small soluble molecules dissolve in dispersion medium then recrystallise onto larger particles causing caking and seal swelling
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Four points on MDI Suspensions. (4)
Used to deliver insoluble drugs. Higher doses can be delivered. Constant aggregation during manufacture is required. Presents phys stability issues.
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Five points on MDI Solutions (5)
Small spray particle size achievable. Positve mixing = perfect mixing. Simple manufac. process. Drug MUST be soluble. Chemical degradation occurs faster
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Advantages of solutions. (5)
Drug available for Abs. Flexible dosing. Any route. No need for pre shake. Swallowing Difficulties.
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Disadvantages of solutions. (5)
Drug stability reduced. Taste. Bulky. Accuracy needed for dosing. Poorly soluble drugs.
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Advantages for Suspensions. (2)
Insoluble drugs can be formulated. higher stability.
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Disadvantages of Suspensions. (3)
Potential crystal growth. Poor dose uniformity. Clogs small orifices
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What does aggregation cause and how is it solved?
poor dose reproducability, reduction in fine particle fraction. solved by bledning propellants so density of mix is that of suspended particles.
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Name three types of surfactant. (3)
Anionic - Oleic Acid. Zwitterionic - Lecithin. Non-ionic - sorbitan trioleate
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What do surfactants add? (3)
Lubrication. Aid homogenous dispersion. Enhance disolution of medication in propellant.
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How do they prevent aggregation? (2)
by adsorption onto solid surface with predominant stabilising mechanism being steric repulsion between hydrophobic chains.
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Name three new surfactants (3)
PEG, Propoxylated PEG, Perfluoroalonic acids
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Five points on spacers. (5)
Slow down droplets. Control inhalation rate. Trap large droplets. Allow droplet evaporation yielding smaller particles. Aid co-ordination.
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Card 2

Front

What are the functions of the respiratory tract?

Back

1) Gas Exchange 2) Cleaning and humidifying of incoming air to prevent lung damage

Card 3

Front

How are large molecules caught in the lung? (1)

Back

Preview of the front of card 3

Card 4

Front

What is inhaled particle deposition dependant on? (6)

Back

Preview of the front of card 4

Card 5

Front

What are the exceptions? (2)

Back

Preview of the front of card 5
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