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SoM 2 sim > Pulmonary Drug Delivery: Deposition > Flashcards

Pulmonary Drug Delivery: Deposition Flashcards

1
Q

What is deposition dependent on?

A
  • physiochemical characteristics of the drug
  • formulation
  • delivery device
  • patient factors
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2
Q

What is the most imporant physiochemical factor of the drug?

A

aerodynamic diameter

diameter of a unit density sphere which settles with the same velocity as the particle in question

depends on size, shape and density

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3
Q

What disperse system is required?

A

monodisperse

GSD = 1

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4
Q

Where would the following sizes of particles be deposited?

> 10mcm

5-10mcm

2-5mcm

0.5-2mcm

? 0.5mcm

< 0.1mcm

A

> 10mcm - throat

5-10mcm - upper airways

2-5mcm - lower airways

0.5-2mcm - alveloar region

? 0.5mcm exhaled without deposition

< 0.1mcm - alveolar region

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5
Q

Why is a smaller particle size required for salbutamol?

A

more than 90% of alpha 2 receptors are located in the pulmonary region

this is where salbutamol acts

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6
Q

Why is beclomethasone more benificial when evenly distributed throughout the lung?

A

beclomethasone is a bronchodilators inhaled steroid

inflammatory cells, such as lymphocytes and macrophages are present throughout the airways as well as the alveolar region

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7
Q

What are the five mechanisms of deposition?

A
  • inertial impaction
  • gravitational sedimentation
  • Brownian diffusion
  • interception
  • electrostatic attraction
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8
Q

Describe inertial impaction.

A
  • particle carried in aerosol stream has its own momentum (mass x velocity)
  • when stream meets obstacle or bend, direction of gas flow changes
  • inertial force of particle resists change in direction
  • particles continue in original direction of motion (larger particles more likely to)
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9
Q

What are the consequences of inertial impaction?

A
  • occurs in upper respiratory tract
  • tends to be large particles (>5mcm)
  • particles swallowed - limited contribution to therapuetic effect
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10
Q

What is gravitational sedimentation?

A

sedimentation due to gravitational force

rate determined by stokes law - directly proportional to particle density and diameter2

occurs in bronchi, bronchioles, alveolar region

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11
Q

What is Brownian diffusion?

A
  • particles smaller than 0.5mcm too small to be deposited by impaction or sedimentation during normal breathing
  • particles bombarded by surrounding molecules in respiratory tract
  • results in movement of particles to low conc areas (eg airway walls)

smaller = more diffusion

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12
Q

What is interception?

A
  • occurs when dimensions of particle are similar to diameter of airways it is passing through
  • particle edge makes contact with airway surface and particle becomes trapped
  • unimportant for spherical particles
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13
Q

What is electrostatic attraction?

A
  • charged particles formed during generation of aerosol
  • induce opposite charge on the wall of the airways
  • attraction between opposite charges = increased deposition
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14
Q

What are barriers to absorption?

A
  • hydrophilic drugs are poorly absorbed through pores
  • rate of absorption of hydrophobic drugs depends on partition coefficient - logP
  • formulation will accept absorption: solutions absorbed quicker than suspensions

physiological:

  • mucus layer on surface of lungs
  • mucociliary escalator
  • macrophage and other cells
  • alveolar epithilium
  • enzymes
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15
Q

Describe the mucus layer

A
  • thin layer of mucus covers wall of respiratory tract
  • first barrier after deposition
  • composition and thickness vary along the length of the respiratory effect
  • consists mainly of water, mucin (GP), carbohydrate, lipid, surfactant
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16
Q

Describe the mucociliary escalator.

A
  • self cleansing through cilia and mucus
  • coordinated movement of cilia propels mucus and material towards pharynx where its swallowed
  • 1L of mucus cleared every 24 hours
17
Q

Describe the marcophages and other cells

A
  • macrophages wander throughout lung - can ingest particles and release peroxides
  • granulocytes migrate to airways - phagocytose material and release proteases
  • lymphocytes - phagocytotic, sensitise lung to future dose
18
Q

Describe the alveolar epithelium

A
  • composed of type I and II cells
  • transport across epithelium by
    • intracellular tight injuctions
    • membrane pores
    • vesicles
19
Q

Describe the enzymes

A
  • metabolic barrier present in every region of lung
  • phase I: oxidation, reduction and hydrolysis
  • phase II: conjugation reactions
20
Q

How does environmental humidity affect deposition?

A
  • humidity higher in lungs
  • condensation of water onto particle occurs as particle moves to high humidity
  • water soluble particles grow in size
21
Q

How does solvent evaporation affect deposition?

A
  • propellant associated with aerosol droplets results in mean emitted size > 40mcm
  • may have insufficient time for propellant evaporation
22
Q

How does chemical composition affect deposition?

A

pMDI drug suspensions may exhibit physical instability

  • flocculation
  • bulk separation
  • irreverisble aggregation
  • crystal growth due to temp cycling (Otswald ripening)

= increased particle size

23
Q

How does aerosol velocity affect deposition?

A
  • larger particles cant change direction
  • large proportion deposits at back of the mouth due to inertial impaction
24
Q

How does respiratory tract physiology affect deposition?

A
  • gender
  • age
  • body size
  • ethnic group
  • pathophysiology
25
Q

How does a spacer device improve deposition for pMDI?

A
  • reduces initial droplet velocity
  • permits propellant evaporation
  • removes need for coordination between actuation and inhalation
26
Q

What is a breath actuated pMDI device?

A

device fires at the correct point of patients inspiratory cycle

27
Q

What can you do about breathing pattern to improve deposition?

A
  • increased inhaled volume = greater peripheral distribution of particles
  • increased inhalation flow rate = increased deposition in larger airways
  • breath holding after inhalation = enhanced deposition by sedimentation and diffusion

rapid inhalation leads to deposition by impaction at the back of the throat

slow, deep inhalation followed by breath-hold

28
Q

What is gamma scintigraphy?

A

measures deposition in ling, oropharynx and stomach

29
Q

What are the four main devices used for assessment of deposition?

A
  • Andersen cascade impactor (ACI)
  • multi stage liquid impinger
  • next generation pharmaceutical impactor
  • single stage glass impinger
30
Q
A

SoM 2 sim (21 decks)

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