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The Medicine Year 3 Sem 1 > Pulmonary Route of Administration > Flashcards

Pulmonary Route of Administration Flashcards

1
Q

Where are particles >1µm likely to deposit?

A

Upper airways

- Enough momentum and mass for impaction and sedimentation

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2
Q

Where are particles which are <0.5µm likely to deposit?

A 
Lower airways (alveoli)
- Brownian diffusion
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3
Q

Where are particles 0.5-1 µm likely to deposit?

A

Nowhere, exhaled out

  • Brownian diffusion only significant for particles <0.5µm there no lower airway deposition
  • <1µm therefore not enough mass and momentum to deposit in upper airways via impaction and sedimentation
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4
Q

Which deposition is directly proportional to particle size?

A

Impaction and sedimentation

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5
Q

Which particle size is deposition by impaction and sedimentation most significant for?

A

> 1µm

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6
Q

Which particle size is deposition by diffusion most significant for?

A

< 0.5µm

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7
Q

When does impaction occur?

A

When a particle with sufficient momentum doesn’t change direction with airflow in a curved airway and impacts on the wall.

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8
Q

What is gravitational sedimentation?

A
  • Particles fall under the effect of gravity
  • Significant between breaths
  • Increase residence time (travel slowly) and decreased breathing rate increases sedimentation
  • Increased by holding breath
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9
Q

What are the factors affecting particle deposition in dry powder products?

A 
Particle:
Diameter
Density
Shape
Charge
Surface chemistry
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10
Q

What are the factors affecting particle deposition in liquid aerosols?

A

Velocity
Propellant type
Droplet size distribution

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11
Q

Where are large particles more likely to be deposited?

A

In the upper airways

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12
Q

Define inertia

A

Property of a particle to resist changes in velocity

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13
Q

When does inertial impaction occur?

A

When the forward momentum of a particle renders it unable to follow the airflow in a curved airway so that it impacts on the wall

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14
Q

Do sub-micron particles have less or more inertia?

A

They have less - they are less likely to impact in the upper or lower airways

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15
Q

What is electrostatic interaction?

A

Charge on particles induces the opposite charge on the airway wall
Accelerates particles into the wall
Rare

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16
Q

What are sprays useful for?

A

Targeting upper respiratory tract

Used in hay fever medication (antihistamines), treatment of sinusitis (steroids), and in decongestants

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17
Q

Do DPIs need a solvent propellant?

A

No - the dry powder is sheared and released when a patient inhales.

Thus no environmental issues.

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18
Q

Where is a drug deposited in the upper airway likely to be absorbed?

A

GI tract - cilia move particles to the throat where they are swallowed so they can be absorbed in the GI

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19
Q

What can be used to enhance solubility in pMDIs?

A
  • Co-solvents e.g. ethanol
  • Inverse micelles
  • Liposomes

Enhances solubility of surfactant propellants

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20
Q

How can pMDI suspensions be stabilised?

A

Surfactants (lecithin, oleic acid)

They adsorb to particles and prevent agglomeration (steric barrier)

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21
Q

How can the valve be lubricated with in pMDIs?

A

Surfactants

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22
Q

What can be used to mask taste of pMDIs?

A

Menthol

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23
Q

What is used as an anti-oxidant in pDMIs?

A

Ascorbic acid

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24
Q

Give an example of a preservative used in pDMIs?

A

Phenylethanol

Benzalkonium chloride

25
Q

What kind of inhalers are needed for small airway diseases?

A

Super fine particle inhalers

26
Q

What are the particle sizes produced by superfine particle inhalers?

A

Ultrafine <100nm)

Extra fine <1µm

27
Q

What 2 factors contribute to most of a dose not being deposited in the lung?

A

Impaction and sedimentation

28
Q

What are the benefits of using smaller particles in small airways disease states?

A
  • Show good efficacy
  • Reduce daily dose of ICS
  • Achieve greater asthma control and QoL
  • Improved therapeutic window
29
Q

What are nebulisers used for?

A

Severe conditions where traditional inhalers can’t be used (hospitals and ambulatory care)
Allow for administration of higher doses

30
Q

Describe the process by which an traditional (air jet) nebuliser releases the drug

A

Compressed air/oxygen exits a narrow office at high velocity.

This creates a negative pressure which draws up liquid from the capillary. where it is aerosolised.

Droplet formed are >40µm.

Larger particles are removed via impaction on a bend. These particles return to the reservoir.

31
Q

Describe the process by which an ultrasonic nebuliser releases the drug

A

Aerosol is created using Piezoelectric crystals.

Piezoelectric transducers vibrating at 1-3MHz focus ultrasound waves in liquid. Intense agitation at focus disperse the liquid to create an aerosol.

32
Q

Describe the process by which a vibrating mesh ultrasonic nebuliser releases the drug

A

Alternating current causes Piezo crystals to expand and contract rapidly. This pulls the mesh into the liquid and then thrusts it forward.

Mono-dispersed superfine droplets are ejected with every forward thrust of the mesh.

Almost all the liquid is converted to an aerosol for inhalation

33
Q

How can you decrease the aerodynamic diameter for DPIs?

A

↓ geometric size
↓ density
↑ shape factor (more asymmetric, needle-like)

34
Q

What is the aerodynamic diameter?

A

Describes dynamic (moving) behaviour of a particle, relating gravitational settling and inertial impaction

Key in determining the location and the extent deposition.

Efficient alveolar delivery of particles with aerodynamic diameters of 1 – 5 µm.

35
Q

Which methods are used for micronisation of drugs for DPIs?

A 
Sieved (200 µm)
Jet mill (2 µm)
Pin mill
Ball mill
CO2 spray crystallized (1 µm)
36
Q

What are the local benefits of pulmonary administration?

A
  • Rapid action
  • Avoids 1st pass metabolism
  • Avoids GI degradation
  • Lower doses needed (less ADRs)
  • Accurate dose adjustment (ideal for PRN medicine)
  • Small volumes (25 - 100ml)
  • Tamperproof container
  • Drug protected from air and moisture
37
Q

Inhalation is used as an alternative RoA if…

A
  • Need to avoid variable pharmacokinetics shown when drug is given orally
  • To treat acute or breakthrough pain
  • Want to avoid chemical/physical interactions with other medication
  • If formulation degraded in GIT
38
Q

What is the upper respiratory tract?

A

Buccal, sub-lingual and nasal cavities
Pharynx
Upper larynx (above the vocal cords)

39
Q

What is the lower respiratory tract?

A

Trachea
Bronchioles
Bronchi
Alveolar ducts

40
Q

Describe the physiology of the lower respiratory tract

A

Trachea branches to primary and then secondary bronchi then to bronchioles which terminate in the alveoli

Diameters:
- Trachea - 2cm
Large diameter allows large particles to travel through
- Bronchioles - ≤ 1mm
- Terminal bronchioles -  ~ 0.5mm
41
Q

Describe the physiology of alveoli

A

300 million alveoli per lung
70 m2 surface area
Large surface area for gas exchange and drug absorption

42
Q

What affects the extent and location of deposition of dry powder particles?

A

Diameter, density, shape, charge, chemical characteristics

43
Q

What respiratory tract features affect deposition of particles?

A

Lung capacity
Geometry of respiratory tract
Breathing pattern (frequency, tidal vol)
Disease

44
Q

What is brownian diffusion?

A

Random collision of particle with airway wall
Significant only for particles < 0.5 µm
Allows deposition to lower airways

45
Q

What is needed for electrostatic interaction to take place?

A

Particle needs to be travelling slowly and to be near the wall

46
Q

Describe interception

A

Particle size similar to airway diameter
Only significant for particles which are asymmetric and needle-like
Become intertwined as a collection

47
Q

Which deposition is inversely proportional to particle size?

A

Diffusion

48
Q

Describe traditional delivery devices

A
  • Deposition achieved impaction and sedimentation
  • Aerosols produces particles with size <10 µm (typically 2 – 8µm)
  • 80-90% of dose not deposited
  • Large losses to GI absorption
    (degraded by GI enzymes, side effects)
49
Q

How do sprays work?

A
  • Electronic actuators give a more controlled dispersion
    (minimises GIT deposition - reduced ADRs)
  • Bidirectional flow
  • The act of blowing shuts off the back of the nasal cavity and prevents disposition into the mouth
50
Q

What are small airways diseases?

A

COPD, Chronic Asthma

Inadequately treated using traditional inhalers due to small airways (<2mm diameter).

Most particles generated in traditional pMDIs and DPIs deposit in the wider upper airways (by sedimentation and impaction).

The smaller (0.5 – 1 mm) particles delivered by the traditional inhalers deposit poorly, most are exhaled.

51
Q

How do super fine particle inhalers work?

A 
Use hydrofluoroalkanes (HFAs) propellant
Produce very small aerosol particles (ultra- and extra-fine particles) which are more likely to be deposited by diffusion.
Less exhaled or swallowed so required smaller dose required
52
Q

What is the limitation of nebulisers?

A

Cumbersome and inefficient

Deliver only ~13% of nebulised drug

53
Q

In what solvent is the drug dispersed in in nebulisers?

A

Polar solvents (usually H2O)

54
Q

Describe passive DPIs.

A
  • Commercially-available.
  • Require quick, strong and deep inhalation.
  • Small drug particles adhered to larger carrier particles.
  • Separated by sheer forces with large particles.
  • Large particles deposited in the oropharynx
  • Smaller particles going down to the lower airways
55
Q

Describe active DPIs.

A

In development

Use an internal power source to aerosolise the powder

56
Q

Give an example of a carrier used in DPIs.

A

Lactose

Not always used - drug crystals may be used
e.g in Pulmicort (budenoside), Turbuhaler (AZ)

57
Q

What are the factors that affect aerodynamic diameter?

A
  • Geometric size (actual size)
  • Density (mass/volume)
  • Aerodynamic diameter (related to particle falling speed)
  • Shape factor
  • P0 = 1
58
Q

What values does the shape factor take?

A

X = 1 for spheres

More asymmetric shapes, X is more than 1
Dividing by a larger number which reduces the aerodynamic diameter

The Medicine Year 3 Sem 1 (7 decks)

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