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Pharmaceutics > Pulmonary RoA > Flashcards

Pulmonary RoA Flashcards

1
Q

Benefits of inhalation medication?

A

rapid onset, avoids first pass, avoids GIT degradation, lower dosage required (less adverse effects), accurate titraition/dose adjustment for individuals, small volumes (25-100mL), tamperproof containers, protection from air or moisture instabilites

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2
Q

How is pulmonary administration a good alternative for systemic administration?

A

avoids chemical/physical interaction with other medication needed concurrently, good when drug exhibits variable/erratic pharmacokinetics on oral administration, useful for acute and breakthrough pain (e.g. fentanyl, morphine), good when there is breakdown in GIT - esp. biologics

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3
Q

Parts included in the upper respiratory tract?

A

Nasal cavity, buccal and sub-lingual

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4
Q

Functions of the nasal cavity?

A

warm moist air, filters out large particles (>15 microns)

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5
Q

What do cilia do in the respiratory tract?

A

Traffic trapped particles to mouth to swallow, or cough/sneeze if big enough

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6
Q

What is the epiglottis?

A

protects the airways when swallowing

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7
Q

What is the blow reflex?

A

isolates nasal pathway when blowing

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8
Q

surface area of the lungs?

A

70 sq m each

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9
Q

how many lobes does each lung have?

A

left = 2, right = 3

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10
Q

average blood flow through the lungs?

A

4-5L per minute

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11
Q

What is multiple branching?

A

The way the airways branch down into tiny ones

modelled with 23 branching (fractal) pathways before alveoli are reached

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12
Q

What product properties affect particle deposition of dry powders?

A

diameter, density, shape, charge, chemical characteristics

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13
Q

What product properties affect particle deposition of liquid aerosols?

A

velocity, propellant, particle size, size distribution,

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14
Q

What respiratory tract properties affect particle deposition?

A

Structure, geometry, presence of disease, breathing patterns, volume changes

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15
Q

What are the mechanisms of drug deposition?

A

impaction, sedimentation, diffusion

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16
Q

What decreases the minimum particle size for deposition?

A

increasing density

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17
Q

Whatsize particles are more likely to be deposited by diffusion?

A

below 0.5 microns

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18
Q

What effect does increasing particle size have on deposition?

A

raises probability of particles being deposited by impaction or sedimentation

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19
Q

Where are larger particles more likely to be deposited?

A

upper airways

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20
Q

What is inertial impaction?

A

when the particle inertia/momentum renders the particle unable to change direction - deposited in curves of airways etc

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21
Q

What types of particles are more prone to intertial impaction?

A

larger, denser

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22
Q

What is gravitational sedimentation?

A

occurs when air velocity is low (e.g. holding breath) due to increased residence time in one region

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23
Q

What is Brownian diffusion?

A

significant deposition mechanism for particles <0.1 microns that are less affected by inertia and gravity, but not useful for traditional inhalers which use larger particles.

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24
Q

What is electrostatic interaction?

A

A charge on the particle induces the opposite charge on the lung wall and accelerates the particle in its proximity

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25
Q

Particle size for effective deposition in lungs in traditional inhalers (and mechanism)?

A

less than 10 microns, typically 2-8

impaction or sedmientation deposition

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26
Q

What are the types of inhalation devices?

A

sprays, pressurised MDIs, super fine particle inhalers, nebulisers, dry powder inhalers

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27
Q

Where do sprays deposit ?

A

upper airways

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28
Q

What happened to pMDIs?

A

CFCs were banned in 1994, so alternative propellants had to be developed

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29
Q

What are super fine particle inhalers used for?

A

small airways disease

developred post CFC ban, so used HFAs as propellant.

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30
Q

What are nebulisers?

A

drug in polar solvent (usually water)

large and less convenient so mainly used in hospital. smaller aerolisation

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31
Q

What mechanism does vianase use?

A

Controlled particle dispersion (CPD)

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32
Q

What is controlled particle dispersion?

A

electronic atomisers provide particle size and direction control

narrow particle size distribution over a range of sizes, turbulent flow controls penetration

minimises GIT and pulmonary deposition

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33
Q

What is controlled particle dispersion?

A

electronic atomisers provide particle size and direction control

narrow particle size distribution over a range of sizes, turbulent flow controls penetration

minimises GIT and pulmonary deposition

34
Q

How do pressurised MDIs work?

A

use liquid propellant gases (HFAs replaced CFCs)

fast moving microfine suspension or solution, requires slow and deep inhalation. patient inhales and valve works simultaneously

35
Q

What are the different types of pressurised MDI?

A

manual valve operation, breath actuated, battery powered

can also have dose counters and electromechanical aspects to improve patient engagement

36
Q

What is used to enhance solubility in pressurised MDIs?

A

Co-solvents - mostly ethanol (also modifies pressure w lower boiling point and enhances solubility of surfactant propellants). can also use inverse micelles or liposomes

37
Q

What is used to enhance wettability in pressurised MDIs?

A

surfactants - finely divide actives and excipients

38
Q

What is used to stabilise suspensions in pressurised MDIs?

A

surface active agents (lecithin, sorbitan trioleate, oleic acid) adsorbed to particles. act as a steric barrier to agglomeration as loose assemblies increase particle size (keeps size uniform)

must shake before use to ensure all is well mix

39
Q

What is used to lubricate the valve in pressurised MDIs?

A

surfactants or simple lubricating oil e.g. food grade silicon oil

prevents friction that would impair valve function

40
Q

What is used as flavouring in pressurised MDIs?

A

menthol often used as a taste marker

41
Q

What is used as antioxidants in pressurised MDIs?

A

sacrifical oxidation - e.g. ascorbic acid

42
Q

What is done about excess moisture inside pressurised MDIs?

A

not sealed systems so water can get in

preservatives are used to prevent microbial growth. benzalkonium chloride (some allergies); phenyethyl alcohol as this can also mask taste/odour

43
Q

Why are inhaler excipients limited?

A

Only certain ones are safe for administration into the lungs

44
Q

Why are small airways diseases poorly treated by traditional inhalers?

A

majority of particles in these inhalers deposit in the upper airways so don’t reach and treat the lungs

  • sedimentation and impaction
45
Q

What is the problem of the smallest particles that can be used in pMDIs? (0.5-1 micron)

A

pass further down into the airways as less likely to deposit in the upper tract, but believed to deposit poorly and are exhaled again

46
Q

What are superfine particles?

A

mix of ultrafine (<100nm) and extra-fine (<1 micron) particles with HFA pMDIs

47
Q

Relationship between sedimentation by impaction/sedmientation and particle size?

A

directly proportional. most effective in particles >1 micron

48
Q

What percentage of the dose is not deposited in large particle size MDIs? consequences?

A

80-90%. large loss to GI absorption, leads to side effects

49
Q

How have traditional pMDIs been improved to increase percentage of deposition?

A

smaller particles emitted at a lower velocity - only 50-70% loss

50
Q

Relationship between particle size and diffusional deposition?

A

Inversely proportional

51
Q

What is the size limit for particles to be deposited by diffusion?

A

less than 1 micron

52
Q

What defines the small airways?

A

<2mm diameter

53
Q

examples of small airways disease?

A

asthma, COPD

54
Q

What clinical evidence is there to support smaller particles?

A
  1. small particles show comparable efficacy (some studies show superiority) with large particles
  2. small particle inhalers achive reduction in inhaled corticosteroid
  3. greater asthma control, improved QoL. less variability between patients
  4. some studies show improved therapeutic ratio with smaller particles
55
Q

Costs and benefits of traditional nebulisers?

A
  • bulky and inefficient, only deliver about 13% of drug, takes longer (20-30 mins)
  • can deliver much higher doses, avoid banned propellants and pressurised gas
56
Q

How do nebulisers work?

A
  • compressed air/oxygen exits a narrow Venturi orifice at high velocity
  • this creates a negative pressure which draws drug containing liquid up from a tube
  • drawn up liquid fragments into an aerosol w particles >40 microns
  • typically a bend in the tube to remove larger particles by impaction (return to resevoir) and smaller ones pass into the lungs
57
Q

Pressure of compressed air in a nebuliser?

A

35-270 kPa

58
Q

What is an ultrasonic nebuliser?

A

turns ultrasound -> kinetic energy

liquid dosage placed over a Piezo crystal

Piezoelectric transducers vibrate at 1-3MHz, and are shaped to focus waves within the liquid

intense agitation at focus -> conical fountain above liquid, which is dispersed to create an aerosol

larger particles still removed by impaction

59
Q

Benefits of ultrasonic nebuliser?

A

less bulky

60
Q

what is a vibrating mesh ultrasonic nebuliser?

A

Mesh shaped piezo that expands and contracts with the voltage - mesh pulled back into liquid then thrown forward. near mono-disperse fine droplets - virtually all liquid is converted to an aerosol appropriate for inhalation

61
Q

Benefits of vibrating mesh ultrasonic nebuliser?

A

very efficient, easily conveted into smart devices controlled by electronics/software to individualise care

62
Q

Example of vibrating mesh nebuliser?

A

Vaping/e-cigs - nebuliser controlled by degree of inhalation to achieve a certain degree of atomisation. heating reduces surface tension.

inhaling sensors activate and switch off device accordingly

63
Q

How is drug formulated in DPIs?

A

Drug alone or on lactose crystals

64
Q

How is drug metered in DPIs?

A

Powder resevoir, blister disk or strip, capsule etc

65
Q

What is passive breath dispersion in DPIs?

A

used in commercially available devices. quick, powerful and deep as possible inhalation

66
Q

What is active dispersion in DPIs and what is it used for?

A

pneumatic impact force and vibratory dispersion, standardises sheer and turbulence = controlled release for narrow therapeutic windows

67
Q

What aerodynamic diameter of particles is absorbed by alveoli?

A

1-5 microns (but inefficient in reaching the alveoli)

68
Q

What factors of particles can be modified in DPIs to change aerodynamics?

A

Size, density and shape (aerosols can only do size)

69
Q

What does aerodynamic diameter describe?

A

dynamic behaviour relating gravitational settling and inertial impaction - decreased by decreasing size/density and increasing shape factor

70
Q

Effect of crystallinity on particle aerodynamics?

A

polymorphs have different solubility, stability and bioavailability

crystal habits - grow in different dimensions which can increase or decrease aerodynamic diameter

71
Q

Effect of hygroscopic properties of particles on aerodynamics?

A

(affected by crystallinity, which adversely affects aerosolisation)

  • irreversible aggregation
  • altered adhesive and cohesive properties
  • increases particle size (due to v high humidity in the lungs)
72
Q

What miling methods are used to produce DPI particles?

A

Jet/ball/pin mills

73
Q

What are inertial cyclones used for in DPI particle production?

A

separate larger particles and

74
Q

What are inertial cyclones used for in DPI particle production?

A

separate larger particles

as classifiers for particle size range separation

75
Q

What alternatives can be used to produce DPI particles if jet/pin mills do not work?

A

Spray drying (more spherical particles, but amorphous) or supercritical fluids (solvents - rapid expansion, anti-solvents - solution enhanced dispersion (smoother particles))

76
Q

What function do excipients have in DPI formulations?

A

Improve dispensing & metering, reduce cohesion (by occupying high energy sites of micronised particles)

77
Q

Why is lactose often used in inhalation formulations?

A

(only one allowed in US)

highly crystalline and smooth surface

78
Q

Contents of canister in single nozzle spray drying?

A

CO2 and drug

79
Q

Contents of canisters in double nozzle spray drying?

A
  1. CO2

2. Solvent + drug

80
Q

Contents of canisters in triple nozzle spray drying?

A
  1. CO2
  2. water + drug
  3. solvent
81
Q

What size particles can be made by sieving, jet milling and CO2 spray crystallisation?

A

sieve- 200 microns
jet mill - 2 microns
spray - <1 micron

82
Q

How are different particle geometries produced?

A

varying process parameters in CO2 spray crystallisatio

Pharmaceutics (5 decks)

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