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PA20320 > Inhalers and deposition > Flashcards

Inhalers and deposition Flashcards

1
Q

What is an Aerosol?

A

A relatively stable suspension of solid/liquid particles in a gaseous medium (0.001mcm-100mcm)

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2
Q

Aerosol behaviour is affected by…

A

Interaction with surrounding air molecules and gravity

It’s own size, shape and density

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3
Q

The target site of aerosolised drugs is …

A

Respiratory bronchioles and alveoli

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4
Q

The pattern of deposition in the lungs…

A

The larger the particle the further up the airways it is deposited with any particle >10mcm getting trapped in the back of the throat

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5
Q

Advantages of inhaled drugs (local delivery)

A
  • Drugs delivered directly to site of action
  • The onset of action is rapid
  • Less drug gets into systemic circulation (For local delivery)
  • Less of the drug is necessary for a therapeutic effect
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6
Q

Advantages of inhaled drugs (systemic delivery)

A
  • Extensive blood supply allows for rapid absorption into systemic circulation
  • Avoids 1st pass metabolism
  • Therefore increased availability
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7
Q

Factors controlling deposition

A

Aerosol properties- size and distribution
Mode of inhalation- volume inhaled, flow rate and breath holding pause
Patient factors- anatomy/physiology differences, respiratory disease

But primarily affected by size and flow rate

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8
Q

Primary deposition mechanisms in the lung

A

Inertial impact (90%)- kinda just smacks into epithelium because they’re moving in a straight line. Mostly large particles

Sedimentation (9%)- the particle moves along slowly, loses energy and plops down. Important for depositing in bronchi

Diffusion (1%)- Particle happily floats along an settles down at a dead end, Earns lots of frequent flyer points. Important for deposition in bronchi/alveoli

The smaller the diameter the further along the resp. tract it gets. Small bois fly far.
Oropharynx>bronchi>alveoli

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9
Q

Secondary deposition mechanisms

A

Interception- where particles contact walls (especially fibres at airway bifurcations

Electrostatic deposition- charged particles can repel each other towards walls

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10
Q

5 essential components of a MDI

A 
Drug
Propellent 
Aerosol canister 
Metering valve 
Atomising nozzle
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11
Q

Suspension based formulation

A

Suspensions preferred due to chemical stability and is capable of delivering high powder loads

Drug must be milled to respirable size <5mcm and must be insoluble

Shaking required to redisperse drug to ensure suspension is homogenous

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12
Q

Role of adjuvant

A

To ensure physical stability of suspension

Must be capable of dispersing and redispersing the drug

Minimise segregation before administration of the drug

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13
Q

Common surfactants

A

SPAN 85, oleic acid and soya lecithins in CFC’s

Oleic acid, magnesium stearate, PEG/PVP in HFA’s

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14
Q

Solution based formulations

A

Suitable if solubility/stability is adequate

Amount of emitted dose is directly related to solubility therefore usually requires a cosolvents as propellants are usually poor solvents

Potential for drugs to recrystallise due to changing temperatures

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15
Q

Problems of solution based formulations

A

Polar co solvent can cause corrosion of Al cannister

Co solvent lowers internal propellant pressure therefore atomisation less effective

Modifying drug to be more soluble is most effective solution

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16
Q

Liquid propellant

A

Good because no loss of pressure after actuations

This because the loss in pressure causes vapourisation of the propellant which restores the pressure within the cannister

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17
Q

Advantages of pMDI’s

A

Consistent dose
Cheap
Resistant to moisture
Compact

18
Q

Disadvantages

A

Patient coordination required
Cold freon effect results in inconsistent delivery
Tail off at the end of a can
High deposition in throat
Very little intellectual property protection for pharm R and D

19
Q

DPI’s (Dry powder inhalers)

A

Driven by patient inspiration

Easy to use Patient/environment friendly

Long term replacement for pMDI’s

20
Q

DPI mechanism of action

A

Inspiration creates energy for fluidisation and entrainment of formulation

Energy caused by pressure drop (deltaP) that s due to inhalation flow (Q) and internal resistance of device (R)

A minimum inhalation flow must be created (Qmin) before dose can be released

21
Q

Relationship between device and airflow

A

R effects speed/acceleration of airflow through the device

Acceleration effects DPI efficacy

Speed affects the amount deposited in the lungs

22
Q

Factors affecting respirable dose

A

R, Q and the powder formulation

23
Q

Particle interactions are dictated by…

A

Van der waals forces

Electrostatic forces

Capillary forces

Contribution of each of these depends on interacting materials and humidity

24
Q

Van der waals forces

A

Dominant at short range in low humidity where there is no electrostatic forces

25
Q

Capillary forces

A

Water condenses between to particles and forms a liquid bridge

Force directly related to humidity and hydrophobicity

Dominant at ambient conditions

26
Q

Electrostatic forces

A

Due to friction between different materials

Long range force

Can be attractive or repulsive and increase at low humidity

27
Q

3 interactions that must be controlled

A

Drug-drug (Cohesion)

Drug-excipient (Adhesion)

Drug-device (Segregation)

28
Q

2 formulation strategies

A

Carrier based- uses adhesion to bind drug to a carrier

Agglomerated- uses cohesion to form an agglomerate which is broken up during inspiration

29
Q

Advantages of carrier based formulations

A

Accurate dosing of small quantities of a potent drug

Improved handling and processing

Carrier size, shape and morphology can be changed to influence fine particle friction (FPF)

30
Q

Advantages of agglomerated powder systems

A

More suitable for high dose drugs

However efficient deaggregation of agglomerate must occur so that drug is presented as discrete particles in the lung

31
Q

Advantages of DPI’s

A 
Propellant free 
No or very little excipients
Large doses can delivered 
In dry form 
Breath actuated
32
Q

Disadvantages of DPI’s

A

Dependant on patients inspiration force

Due to higher velocity there is increased chance of inertial impaction

Exposure to ambient conditions can reduce stability

Less efficient at delivery than a pMDI

33
Q

Nebulisers

A

A drug contained within a sterile solution

Significant variation occurs a lot drug being left within the device, in expiration and many particles are to small or large

As little as 10% of the target dose maybe delivered

34
Q

Pneumatic nebuliser

A

Works by using a high velocity air jet to blow air very quickly causing them to break into small particles

A baffle (inertial filter) traps oversized particles

35
Q

Pneumatic nebuliser pros and cons

A

Cheap and can achieve small particle sizes

But: has variable performance
Dead (stagnant) volume
Lower output
Not very portable

36
Q

Ultrasonic nebulisers

A

Uses a piezoelectric ceramic disc which oscillates and causes droplet production

37
Q

Ultrasonic nebuliser pros and cons

A

Consistent
Produces small particles
High output
Small and quiet

But: low inertia
particle size increases at end of life 
expensive 
heats solution to 40 degrees celsius 
Unsuitable for suspensions
38
Q

Soft mist inhalers (SMI’s) and Liquid dose inhalers (LDI’s)

A

Based on a drug dissolved in non volatile liquid
Volumetric dosing
Breath actuated
Dose emitted as a slow moving cloud

39
Q

AERx LDI

A

A hand held nebuliser

Uses an actuater to extrude drug, held in 50mcl through tiny micron sized holes

Microelectronics guide patient for optimum inspiration

40
Q

Respimat mechanism

A

Drug stored in solution

Solution is forced through micro nozzle as patient inhales

41
Q

Respimat advantages

A

Avoids moisture problems and powder aggregation that can occur with DPI’s

Can deliver a metered dose

PA20320 (15 decks)

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