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Pharmaceutics > Inhalation Drug Delivery > Flashcards

Inhalation Drug Delivery Flashcards

1
Q

What are the benefits of inhalation drug delivery?

A
  • rapid onset of action - good for breakthrough pain
  • avoids GI degradation - good for compounds that are prone to this
  • avoids first pass metabolism
  • can use a lower dose of the drug, meaning fewer/less risk of ADR
  • accurate dose adjustment and titration, good for when required dosing
  • use of small volumes (25mL - 100mL)
  • good to avoid physical/chemical interactions
  • good for when a drug has issues orally with it’s pharmacokinetics (unpredictable/inconsistent)
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2
Q

What parts of the airway consists of the upper respiratory tract?

A
  • buccal
  • sublingual
  • nasal cavities (this warms and moistens the air an filters out large particles)
  • pharynx
  • larynx
  • epiglottis
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3
Q

What parts of the airway consist of the lower respiratory tract?

A
  • trachea
  • bronchi (primary and secondary)
  • bronchioles
  • alveoli
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4
Q

What is the diameter of the trachea?

A

1.5cm - 2cm

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5
Q

What is the diameter of the bronchioles?

A

< 1 mm

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6
Q

What is the diameter and surface area of the alveoli?

A

< 0.5 mm

have 30 million alveoli per lung, giving a 70cm2 surface area for gas exchange

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7
Q

What is particle deposition affected by?

A
  • product characteristics

- anatomical and physiological characteristics

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8
Q

What product characteristics affects particle deposition?

A 
Dry Powder (particles)
- diameter, shape, density, charge, surface chemistry 
Liquid Aerosol (liquid droplets) 
- droplet size, velocity, nature of propellant
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9
Q

What anatomical and physiological characteristics affect particle deposition?

A
  • lung capacity
  • lung geometry
  • breathing pattern (frequency + tidal volume )
  • disease/pathology
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10
Q

What particle size-related effects are there when considering particle deposition?

A
  • inertial impaction
  • gravitational sedimentation
  • brownian diffusion
  • electrostatic attractions
  • interception
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11
Q

What is inertial impaction?

A
  • related to bigger sized particles (above 1um - micron in size)
  • momentum of the particle means that it doesn’t follow the airflow and instead impacts on the wall
  • bigger particles move faster
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12
Q

What is gravitational sedimentation?

A
  • this is where particles sediment in the gap between breathing in and breathing out
  • related to the residence time in an airway and terminal settling velocity
  • also related to bigger sized particles

this is increased when someone holds their breath

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13
Q

What is brownian diffusion?

A
  • related to smaller particles (below sub micron sized < 0.1 um)
  • random collision of a particle with the airway wall
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14
Q

What is electrostatic attraction?

A
  • where the charge on the particle induces a charge on the airway wall
  • this happens further down the airways as particles have to be close to the wall in order to induce a charge
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15
Q

What is interception?

A
  • where the particle size approaches the same diameter as the airways and deposit through interception
  • this is not significant for spherical shaped particles
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16
Q

What types of particles are impaction and sedimentation relevant to?

A
  • larger particles over 1um in size
  • effect of the process is PROPORTIONAL to the size of the particle
  • the bigger the particle, the bigger the effect of the process on particle deposition
17
Q

What types of particles is diffusion relevant to?

A
  • smaller particles that are sub micron size, less than 0.1um
  • effect of the process is INVERSELY proportional to the size of the particle
  • the smaller the particle, the bigger the effect of the process on particle deposition
18
Q

What different types of inhalation devices are available?

A
  • sprays (useful for the Upper Respiratory Tract)
  • pDMIs (uses solvent propellents, used to be CFCs and is now HFAs)
  • Superfine Particle Inhalers (developed for small airways disease, uses HFA to produce very small particles)
  • Nebulisers (mostly used in hospitals, the drug is dispersed in a polar solvent, usually water)
  • Dry Powder Inhalers (these are replacing pDMIs as they do not use a solvent propellant at all, the powder fluidises as the patient inhales and the drug shears from larger particles so that it can penetrate deeper in the lungs)
19
Q

What deposition is achieved with traditional delivery devices?

A

these formulations produce particle sizes of <10 um, between 2 and 8um
- this means that deposition is primarily achieved through impaction and sedimentation

80 - 90% of the dose is lost and NOT deposited, lots of GI absorption leading to side effects

newer devices produce smaller particles that travel at a lower velocity, so that you get over 30 % deposition

20
Q

Nasal Sprays - Upper Respiratory Tract

A
  • metered dose pumps, actuator released causes the dip tube to fill with formulation for next dose
  • VIANASE, controlled particle dispersion (10-30um) to minimise GI and Pulmonary deposition so that it only goes to the nose
  • OPTINOSE, bidirectional flow (when a patient blows out, soft pallet closes and shuts the nasal cavity from the throat to prevent any deposition elsewhere)
21
Q

pressurised Metered Dose Inhalers (pMDIs) - Lower Respiratory Tract

A
  • uses a liquid propellant (HFA)
  • generates fast moving micro-fine suspensions
  • slow and deep inhalation
  • valve and inhalation at the same time
    (manually/breath-actuated/battery-activated)
  • dose counters incorporated
22
Q

What are the excipients of a pDMI?

A
  • co-solvent/inverse micelles/liposomes to enhance solubility of surfactants
  • surfactants to adsorb particles and prevent agglomeration (shake before use)
  • menthol for flavouring
  • ascorbic acid as an antioxidant
  • phenyl ethanol for an antimicrobial preservative
23
Q

MDI Case Study: 20um particles

A
  • larger particles likely to deposit in the UPPER airways by impaction and sedimentation (if the flow rate is low)
  • large particles, big mass, so will deposit and not a lot will be exhaled
  • upper airways are ciliated, meaning that drug deposited here will be moved up to be swallowed meaning there will be drug absorption in the GI tract
24
Q

MDI Case Study: 6um - 2um particles

A
  • these particles are smaller in size and will have less momentum, so will not impact in the upper airways as it is less branched, more likely to further down
  • a larger amount of the 6um will be deposited than the 2um as the particles are bigger and less likely to be affected by the air flow
  • these particles are too large to be influenced by Brownian diffusion
25
Q

MDI Case Study: 0.6um particles

A
  • small particle, with low mass and momentum
  • will not deposit through impaction or sedimentation as the mass is too low
  • some MAY deposit through brownian diffusion, but this effect is only really seen with particles that are sub-micron size
  • no mechanisms of deposition means that the particle will be exhaled
26
Q

What has now taken over the MDIs since the ban of CFCs?

A

SUPERFINE PARTICLE INHALERS

27
Q

What are superfine particle inhalers used for?

A

small airways disease (asthma/COPD)
these are inadequately treated with traditional inhalers:
- larger particles produced deposit in the upper airway through impaction and sedimentation
- the smaller particles produced do not deposit at all, as they are too small to deposit through impaction and sedimentation but not small enough to be affected by Brownian diffusion

28
Q

What size particles do superfine particle inhalers produce?

A

extrafine (less than 1um)

ultrafine (less than 100nm)

29
Q

What are the benefits of superfine particle inhalers?

A
  • allows for a reduction in the daily dose of inhaled corticosteroids, giving better management and quality of life
  • the superfine particles when formulated with HFA instead of CFC lead to improved treatment
30
Q

Nebulisers

A
  • used at home and in hospitals that suffer with conditions that are unable to be treated with other inhalers
  • inefficient and only deliver 13% of the nebuliser drug
  • BUT allow for administration of higher doses
31
Q

What are the three different types of nebuliser?

A

Traditional Air Jet Nebulisers
Ultrasonic Nebulisers
Vibrating Mesh Ultrasonic Nebulisers

32
Q

Traditional Air Jet Nebuliser

A
  • compressed air goes through a hole at high velocity
  • draws in the liquid to a tube
  • liquid is aerosolised
  • gives LARGE droplets of 40um that impact onto the bends in the equipment
33
Q

Ultrasonic Nebulisers

A
  • ultrasound waves in liquid
  • intense agitation
  • disperses the liquid and forms an aerosol
34
Q

Vibrating Mesh Ultrasonic Nebulisers

A
  • mesh into the liquid
  • thrusts forward and creates a mono disperse aerosol of superfine droplets
  • much smaller droplets that is better for use
35
Q

Dry Powder Inhalers

A

Passive Breath-Dispersing Devices

require quick strong deep inhalation

  • small drug particles carried on larger carrier particles
  • when inhaled, larger carrier particles impact to the back of the mouth and throat
  • this shears of the drug particles, that travel further down the airways

Active DPIs where an internal power source would aerosolise the powder is et to be commercially available

36
Q

What are the various metering devices of Dry Powder Inhalers?

A
  • Powder Reservoir
  • Blister Disk
  • Blister Strip
  • Capsules
37
Q

What is aerodynamic diameter?

A

describes the dynamic behaviour of a particle, relating gravitational settling and inertial impaction

  • determines where in the respiratory tract the particle will deposit
38
Q

What aerodynamic diameter gives efficient alveolar delivery of particles?

A

1 - 5um

39
Q

What factors can decrease aerodynamic diameter?

A
  • decreasing geometric size
  • decreasing density (making a particle more porous, but the same size)
  • increasing the shape factor (making more asymmetric or needle like) - X needs to be more than 1

Pharmaceutics (6 decks)

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