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Amy Somerville > RESP - D. DELIVERY SYSTEMS-COVERED > Flashcards

RESP - D. DELIVERY SYSTEMS-COVERED Flashcards

1
Q

what is an aerosol

A

dispersion of solid particles of liquid droplets in a gas
need energy to form an aerosol

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2
Q

what are the 3 types of inhalers

A
  1. nebulisers
  2. pMDI - stored in pressure off solid (most common)
  3. DPI - no pressure. energy source is the the force of inhalation
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3
Q

Nebulisers

A
  • aq drug solution/suspension aerosolised into droplets
  • energy provided by compressed air or ultrasound
  • not portable
  • can deliver a large dose but it’s not a unit dose
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4
Q

pMDI

A
  • drug formulated in a liquefied gas under pressure
  • aerosol formed by evaporation of gas at atm
  • produces a unit dose on each actuation
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5
Q

DPI

A
  • drug with solid excipients in a dry powder state
  • aerosolisation by patient’s inhalation
  • produces a unit dose on each actuation
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6
Q

Jet nebuliser (or atomizer)

A
  • air from compressor forced through a narrow hole to give a high velocity air stream
  • air stream breaks drug solution/suspension into droplets for inhalation
  • baffles removes larger particles
  • mask/mouthpiece used
  • energy source = compressed air
  • involves a pump and power source
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7
Q

Ultrasonic nebuliser

A
  • piezoelectric crystal emits a high frequency ultrasound that breaks a drug solution/suspension into droplets for inhalation (electric charge which creates sound waves - vaporises liquid)
  • particles in suspension may be degraded by ultrasound as lots of energy put in
  • suspension: inhale undissolved particles (≤5 microns)
  • solution: droplets (≤5 microns)
  • lighter and quieter than jet nebuliser
  • no pump
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8
Q

how to use nebulisers

A
  • patient breathes normally into facemask/mouthpiece
  • good for children and elderly
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9
Q

advantages of nebulisers

A
  • aq drug solutions used (easy or soluble drugs)
  • no hand-lung co-ordination needed
  • no controlled inhalation manoeuvre
  • large doses can be given
  • low cost
  • visible mist - patient reassured
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10
Q

disadvantages of nebulisers

A
  • not fully portable
  • equipment not yet fully regulated
  • lengthy nebulisation time (1 hour)
  • low efficacy: 10% drug reaches lungs
  • solution concentrates as water evaporates
  • insoluble drugs require surfactants or use suspension
  • suspension can be difficult to nebulise
  • microbiological contamination: chance of infection
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11
Q

pMDI canister

A
  • withstand high pressure
  • robust (resistant to damage)
  • light in weight (steel/aluminium)
  • inert and non-stick (internal surface coated to prevent drug adhesion/degradation)
  • aluminium/stainless steel
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12
Q

pMDI metering valve

A
  • ensures accurate and reproducible volume of drug
  • 25-100 microlitres
  • if want more drug: DPI
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13
Q

pMDI propellant

A
  • liquid under pressure (3-5 atmospheres)
  • gas at atmospheric pressure and ambient temperature - low bpt (liquid boils to form gas)
  • vapour pressure must stay constant (dose uniformity)
  • non-flammable and non-toxic
  • chemically inert and compatible with drug formulation
  • chlorofluorocarbons were used
    ozone depleting gases
    banned
    responsible for cold-freon effect
  • hydrofluoroalkanes
    drugs needed to be reformulated due to different properties of HFA vs CFC
    new valve materials
    reduce carbon footprint of MDI by 90% to a level similar to a DPI
    HFA-152a
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14
Q

pMDI drug aspects

A
  • dose per actuation = 5micrograms - 5mg
  • particle (droplet) size of drug: <5microns needed
  • drug substances usually large solid particles when manufactured (100microns - allow good flow) and poly disperse so size reduction required:

milling
micronisation
can change physical form of drug - can lead to polymorph change (different solubility and stability and hence bioavailability), degradation due to heat and formation of amorphous material

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15
Q

pMDI drug formulation

A
  • soluble in propellent
  • insoluble in propellent:
    micronised drug particles suspended in propellent
    surfactants added to increase suspension stability
    (most common)
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16
Q

pMDI suspension formulation

A
  • each volume of suspension must be homogenous
  • surfactants aded to improve stability/homogeneity of suspension and aid in formation of a flocculated suspension (easily redispersible)
    oleic acid, lecithin
    if insoluble in HFA - ethanol as co-solvent to solubilise them
17
Q

problems with suspensions

A
  1. sedimentation
    - non-homogeneity
  2. flocculation
    - reversible aggregation (good if controlled)
  3. caking
    - clumping in layer
    - hard to redisperse
  4. particle size growth by Ostwald ripening
    - large particles grow at expense of smaller ones
    - small crystals dissolve, and redeposit onto larger crystals
18
Q

how to minimise caking

A

controlled flocculation:
- slow flocculation (patient shakes, doesn’t immediately sediment out, time to use device)
- slow sedimentation
- easy redispersion

always shake before use to redisperse settled flocculates

19
Q

excipients that can be included in a pMDI

A
  • flavours: mask bitter drugs
  • sweeteners: mask bitter drugs
  • lubricants: improves valve operation (surfactants?)
  • density modifiers: decrease sedimentation rate
  • anti-oxidants: prevent chemical degradation (esp liquids)
20
Q

why is co-ordinating activation with inhalation so difficult for patients

A
  • due to the speed of drug release (0.1 seconds)
  • particles leave at high velocity
  • therefore get high deposition in oro-phayrnx and low deposition in lung
21
Q

how does a spacer help with improving inhalation with pMDI

A
  • doesn’t suspend med for an extended period
  • so still need to co-ordinate to an extent their breath to begin slightly before actuating pMDI
22
Q

how does a valve holding chamber device help with improving inhalation with pMDI

A
  • added-one way valve which prevents medication loss if patients exhales into device
  • traps and suspends particles long enough to be inhaled over a few seconds
23
Q

advantages of spacer and VHC devices

A

increased lung deposition
- delay actuation and inhalation
- decrease velocity of spray (less back of throat)
- more time for propellant to evaporate (get rid of taste)

24
Q

disadvantages of spacer and VHC devices

A
  • cumbersome
  • decreases dose inhaled due to deposition in device
25
Q

breath-actuated pMDI

A
  • inhaler fired patients inhalation
  • no co-ordinated needed
  • aerosol still leaves inhaler at high velocity so some loss
    Easibreathe (some include a dose counter)
26
Q

advantages of pMDIs

A
  • compact, portable, robust, convenient
  • multi-dose
  • short treatment time
  • consistent format and operation for all pMDIs
  • dose uniformity
  • good protection against moisture and pathogens
  • inexpensive
  • simpler formulation than DPI
27
Q

disadvantages of pMDIs

A
  • no breath-actuation so need coordination
  • low lung deposition
  • no dose counter
  • only low doses (5micrograms - 5mg)
  • need priming before use
  • not environmental friendly
28
Q

DPIs

A
  • no solvent involved
  • can deliver larger dose (20mg)
  • breath-actuated so no co-ordination required
  • more stable as no water to promote chemical reactions
  • store <30 degrees Celsius
29
Q

main components of a DPI

A
  • drug powder/ bend with excipients
  • drug reservoir or pre-metered doses (cartridge, blister, capsule)
  • body
  • cap to protect from dust and moisture
30
Q

what does the patients inspiratory flow do in DPIs

A
  • fluidises the static powder blend
  • deaggregate particle agglomerates into inhalable particle

(drug deposited depends on inspiratory flow)

31
Q

DPI powder de-aggregation

A
  • particles <5 microns are very cohesive due to large SA:mass ratio
  • moisture increases agglomeration

so

  1. drug blended with a carrier powder (50-100mm) with large particle size (lactose) = ORDERED MIX
    - flows well as large
    - drug must be separated from this carrier particle to be inhaled
    - large carrier particles deposit in oro-pharynx and swallowed
    - drug deposits in lungs
    *particles can’t segregate due to size differences as they are adhered to each other. Only if a force is applied - turbulent flow on inhalation
  2. spherical particles (spray-dried powders) can reduce particle contact area and hence aggregation
  3. protection from moisture (blister pack)
32
Q

what are the 3 types of DPI

A
  1. unit dose devices
  2. multiple unit dose devices
  3. reservoir devices
33
Q

Unit-dose DPI

A
  • drug and excipient in capsule
  • capsule inserted into device
  • capsule pierced by pins as closed
  • patient inhales blend (SLOW AND DEEP)
  • have to refill
  • good dose uniformity

Aerolizer
Handihaler

34
Q

Multi-unit dose DPIs

A
  • drug and excipient in blisters
  • 4-8 unit doses on a disk - Discinhaler (rotates)
  • Diskus has a coiled strip of 60 double foil-wrapped individual doses (1 month supply) and a dose counter
  • blisters pierced by moving lid/ratchet mechanism
  • disk/strip discarded when empty
  • not refillable - dispose
35
Q

multi dose reservoir DPIs

A
  • drug/blend only in a compartment within device
  • drug dispensed into dosing chamber by patients action: twist shaves material off a pellet of the powdered drug
  • disposable one use only
  • powder equivalent to a pMDI
  • dose uniformity not as good and drug exposed to humidity (1 reservoir)
  • need a stronger inhalation than multi-unit dose DPI

Turbohaler
Easyhaler

36
Q

advantages of DPIs

A
  • compact, portable, convenient
  • breath-actuated - no coordination
  • higher doses than pMDI
  • dose counter
  • dry state so better stability
  • environmentally friendly - no propellants
37
Q

disadvantages of DPIs

A
  • breath-actuated - need sufficient force
  • can’t be used by young children
  • different designs
  • affected by ambient humidity
  • need to get balance of particle carrier and drug particle adhesion and seperation
  • expensive

Amy Somerville (70 decks)

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