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PHAR 224 > Aerosols > Flashcards

Aerosols Flashcards

1
Q

What are some potential disease indications for aerosol dosage forms?

A

Angina (Nitro Spray), Xerostomia (Biotene Spray)

Nasal spray, MDI & SMI inhalers (aerosols are commonly used for respiratory conditions)

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2
Q

What are some desired characteristics of aerosol preparations?

A
  • Dose counter (improves adherance)
  • Easy to use
  • Portability (especially if device needs to be on hand)
  • Device safety
  • Resistant to contamination
  • Large supply of dose
  • Dose accuracy
  • Cost effective
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3
Q

What is the definition of an aerosol dosage form?

A

An aerosol is a dispersion of solid or liquid particles (typically less than 50mcg diameter) in a gas

The small particle size of the dispersed phase is critical for the proper deposition of drug into the lung

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4
Q

How many people recieve aerosol therapy?

A

300 million patients with Asthma alone, so number is even higher when including patients receiving treatment for other respiratory conditions like COPD

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5
Q

What is the benefit of using a spacer with an MDI device?

A

Can improve delivery to lungs (target) more effectively compared to MDI alone

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6
Q

What are some advantages of aerosol dosage forms?

A
  • Directly administered to the affected area
  • Rapid onset
  • Dose regulated/metered
  • No contamination
  • Sensitive materials are protected from the environment
  • Minimized irritation
  • Alternate route of administration (fewer side effects and drug interactions)
  • Convenient and easy to use
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7
Q

What are some limitations associated with aerosol dosage forms?

A
  • Variability of the bioavailable dose of the drug (coordination and penetration problems)
  • Rapid clearance (macrophages in the lungs breakdown drug)
  • Drugs with low water solubility can cause local irritation
  • Low intracellular penetration of drugs
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8
Q

What are the different types of aerosol preparations?

A
  1. Inhalations (drug admin via respiratory route)
  2. Insufflators (powder is carried into the respiratory tract)
  3. Inhalants (drugs with high vapour pressure and can be inhaled through nose)
  4. Nebulizers (used for inhalation therapy in hospital)
  5. Vapourizers (produce steam for humidification)
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9
Q

What are the two types of inhalation devices used in pharmacy?

A

Pressurized devices

Non-pressurized devices

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10
Q

What are the main components of a pressurized inhalation device?

A
  • Aerosol formulation (propellant + product concentrate)
  • Container
  • Valve and actuator
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11
Q

What is the utility of propellants in pressurized aerosols?

A
  • Develop the proper pressure within the container
  • Expel the product
  • Aid in atomization or foam production
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12
Q

What are some types of propellants used in pressurized inhalation devices?

A

All should have low vapour pressure (gaseous at room temperature)

  1. CFC (rarely used, need exception to use due to environmental concerns)
  2. HFA (most common)
  3. Hydrocarbons (limited use)
  4. Compressed gases
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13
Q

What are some characteristics of CFCs?

A
  • Environmental concern (used when other propellants cannot be substitued)
  • Chemically inert and not toxic at prescribed doses
  • Non-flammable
  • Non-polar
  • Capable of dissolving many substances (especially non-polar drugs)
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14
Q

What are some characteristics of HFAs?

A
  • Alternative to CFCs
  • Non-flammable
  • Non-ozone depleting (better for environment)
  • Chemically inert and non-toxic
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15
Q

What are some characteristics of hydrocarbon propellants in inhalation devices?

A
  • Suitable replacement for CFCs
  • Flammability restricts their use
  • USed in foam and water-based aerosols only

ex. propane, butane, isobutane

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16
Q

What are some characteristics of compressed gas inhalation devices?

A
  • Limited value for aqueous products
  • As volume of preparation decreases with use, the pressure at which drug is delivered also declines. (dose variability)

ex. Nitrogen, nitrous oxide, carbon dioxide

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17
Q

What are the components of a pressurized device?

A
  • Aerosol Formulation
  • Propellant
  • Product concentrate (solution, suspension, or emulsion)
  • Container
  • Valve and Actuator
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18
Q

What are the three categories of product concentrates used in pressurized devices?

A
  1. Solution Systems
  2. Suspension Systems
  3. Emulsion Systems (three phase system)
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19
Q

What are the characteristics of solution systems as product concentrates?

A

Phase 1: Solution of active ingredients in liquified propellant

Phase 2: Vapourized propellant

When the valve is activated, the pressure of the vapour phase causes the liquid phase to rise in the tube to be expelled from the container

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20
Q

What are the characteristics of suspension systems in pressurized devices ?

A

Similar to solution systems in that they have two phases.

But in suspension systems, active ingredients are in suspension of the the propellant

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21
Q

What are the characteristics of emulsion systems in pressurized devices?

A

These systems contain three phases (active ingredient, liquid propellant, and gas propellant)

Two different types:

  1. Foam (o/w emulsion)
  2. Spray (w/o emulsion)
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22
Q

What are the characteristics of foams from pressurized devices?

A

Type of emulsion system

  • Propellant in the internal phase (o/w emulsion)
  • 7-10% propellant used

ex. steroid foams, burn and other topical preparations

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23
Q

What are the characteristics of spray emulsions from pressurized devices?

A

Type of emulsion system

  • Propellant in the external phase (w/o emulsion)
  • Contain 25-30% propellant
  • No foaming
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24
Q

Can glass containers be used for inhalation therapy devices?

A

No, only metal containers are used for inhalation therapy devices

Glass containers are used for topical preparations

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25
Q

What are two types of valves used in aerosol devices?

A
  1. Continuous valves
  2. Metered valves
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26
Q

What are some characteristics of continous valves used in aerosol devices?

A
  • Used in topical preparations (foams especially)
  • Medication is deispensed continously while valve is being pressed (allows for dose control)
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27
Q

What are some characteristics of metered valves used in aerosol devices?

A

Two different types based on the placement of container:
a. Upright use
b. Inverted use

These types of devices administer a specific amount of drug for a given actuation

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28
Q

What are some limitations with metered valve aerosol devices?

A

There is considerable product loss during actuation (issues with device technique and device design)

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29
Q

What type of valve is often used in MDIs?

A

Inverted use valves (container is inverted when inserted into device)

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30
Q

Do MDIs have almost no product loss?

A

No, it is a metered valve so it can actually loose 75% of the drug before it can reach the lungs

10% is lost to the inner surface of the adapter

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31
Q

What is the most common inhalation aids used with MDIs?

A

Spacers (can be used by kids and adults)

Especially useful for unconcious patients or those with poor coordination of actuation and inhalation

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32
Q

What is the benefit of spacers?

A

Spacers may enhance the delivery of the medicine and make it easier to coordinate the spray with breathing

Drug reaches the lungs more completely and efficiently when using a spacer vs. without one

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33
Q

What are the two main types of non-pressurized inhalation devices?

A
  1. DPIs (dry powder inhaler)
  2. SMIs (soft mist inhaler)
34
Q

In general, how do soft mist (non-pressurized) devices work?

A
  • Devices are pre-loaded with solution of medication
  • Uses spring to deliver “soft mist” of medication (use the breath to draw drug into lungs
35
Q

What are some an example of a soft mist (non-pressurized) device?

A

Respimat (Tiotripium (LAMA) & Olodaterol (LABA))

Need to shake and prime before use (especially if patient uses inhaler infrequently)

36
Q

What are some examples of breath-activated powder inhaler devices (non-pressurized)?

A
  • Turbuhaler
  • Handihaler
  • DISKUS
37
Q

What is a unique characteristics of the Genuair device (powder inhaler devices)?

A

Makes a clicking sound once dose has been taken correctly (Improves patient confidence in their technique and product)

38
Q

What type of inhalation device is most commonly used for asthma and COPD and what are its advantages?

A

pressurized MDIs

39
Q

What are some advantages associated with pressurized MDIs?

A
  • Portable
  • Compatible with spacers
  • Multi-dose convenience
  • Reproducable dosing (no decline as device empties)
  • Difficult to contaminate (due to device design)
40
Q

What are some disadvantages of pressurized MDIs?

A
  • Considerable product loss
  • Hand-inhalation coordination is required
  • Proper inhalation (breath holding is required for at least 5 sec)
  • Reaction to propellants
  • Difficult to determine the dose remaing in the canister
41
Q

What are some advantages associated with DPI use (non-pressurized)?

A
  • Great for patients who have difficulty corrdinating inhalation and actuation
  • Most come with built-in dose counter
  • Uses no CFC or propellants for that matter
42
Q

What are some disadvantages associated with DPIs?

A
  • Variable inspiratory flow rate causes a large dose variability
  • Some patients do not like the gritty sensation/taste
  • Requires adequate inspiratory drive (may be compromised depending on condition being treated)
43
Q

What are the advantages of soft mist inhalers?

A

Reduces the requirements for patient coordination and inspiratory effort, and improve patients’ experience and ease of use

Offer higher lung deposition of drug and lower oropharyngeal deposition

44
Q

What are some disadvantages of soft mist inhalers?

A

Cost and need for priming

45
Q

What is a major advantage of nebulizers?

A

Less dependent on patient coordination or cooperation

Nebulizers use a compressor to aerosolize liquid medication (similar in action to MDI + spacer)

46
Q

Which patient groups can recieve the most benefit from nebulizer therapy?

A
  • Very young, old, debilitated, or distresssed patients
  • Patient coordination/breath is compromised like emergency treatment for acute asthma and COPD
  • Prophylactic drug treatment for asthma
  • Antibodies for cystic fibrosis, bronchiectasis, and HIV/AIDS
  • Symptom relief in palliative care
47
Q

What are some disadvantages associated with nebulizers?

A
  • Not easily portable
  • Expensive equipment
  • Long nebulization times to ensure aequate drug delivery (vs. other devices that deliver full dose in seconds)
48
Q

What are the different types of nebulizers?

A
  1. Jet nebulizers
  2. Ultrasonic nebulizers
49
Q

How do jet nebulizers work?

A
  1. Pressurized jet air stream enters through a narrow tube and is forced through a narrow opening called the venturi
  2. The jet stream caused a pressure drop near the venturi
  3. Decreased pressure near the venturi causes liquid drug in the reservoir to be sucked up through the liquid feeding tube
  4. The sucked liquid is broken into droplets by the jet stream
  5. Small droplets are pushed by the jet stream out od the nebulizer as a fine mist

Review slide 55 for a diagram and explanation

50
Q

How do ultrasonic nebulizers work?

A

They produce aerosolized droplets using high-frequency sound waves

Droplet size (determined by the frequency of the sound waves, higher frequencies = smaller droplets)

51
Q

What are some characteristics of the mouthpiece attachment for nebulizer systems?

A

Preferred method (delivery increases by up to 85%)

Reduced contact of drug beyond the internal respiratory system

52
Q

What are some characteristics of the face mask attachement for face mask for nebulizer systems?

A

Drug in contact with skin; wash face after administration (contact with eye can occur and cause increased IOP)

Only device that can administer inhaled drugs to infants

53
Q

What are the goals of therapy for inhalation therapy?

A
  • Improved strength of respiratory function
  • Bronchodilation in an asthmatic
  • Liquefaction of mucus in a person with chronic obstructuve lung disease (COPD)
54
Q

What characteristics of inhalation therapy are beneficial in delivering drug to the lungs?

A
  • Therapeutic drug concentrations at local sites alone (limited systemic exposure)
  • Dose can be minimized
  • Low cost of therapy (depends on type of inhaler)
55
Q

What are some indications of inhalation therapy?

A
  • Bronchodilation (aerosols)
  • Decongestion (vapours/aerosols)
  • Inflammation (aerosols)
  • Systemic drug delivery (aerosols)
56
Q

What are some characteristics of cystic fibrosis?

A
  • Caused by genetic mutation
  • Salty-tasting skin
  • Cough with sputum production
  • Chronic airway infections (bronchiectasis)
57
Q

What types of drugs are given to cystic fibrosis patients with inhalation therapy?

A

Nebulizers are often the recommended devices used for inhalation therapy in CF

  • Dornase alfa (recombinant human DNA cleaver targets white blood cells to thin mucus)
  • Antibiotics (tobramycin, azithromycin)
  • Inhaled hypertonic saline, ICS
  • Inhaled bronchodilators
58
Q

What are the main structures of the lungs?

A
  1. Pharynx
  2. Trachea
  3. Bronchi
  4. Respiratory bronchioli
59
Q

What factors impact the efficiency of inhalation therapy?

A
  • Particle sizes (larger particles will not reach deeper parts of respiratory system)
  • Speed of inspiration
  • Patient factors (lung capacity, coordination)
  • Aerosol container factors (storage, propellant use)
  • Pulmonary clearance of the drug (macrophages line the lungs)
60
Q

What are the three mechanisms of drug deposition in the lungs?

A
  1. Inertial impaction (occurs with fast moving particles larger than 3 micrometers)
  2. Gravitational settling (function of particle mass and time, with the rate of settling proportional to particle size and mass)
  3. Diffusion (occurs with particles smaller than 1 micrometer)
61
Q

What happens to particles that are larger than 10 micrometers when inhaled?

A

They are filtered in the nose and/or the oropharynx largely due to inertial impaction

62
Q

What happens to particles between 5-10 micrometers when inhaled?

A

Particles of this size reach the proximal generation of the lower respiratory tract

63
Q

What happens to particles between 1-5 micrometers when inhaled?

A

They will reach the lung periphery

64
Q

What happens to particles with sizes below 1 micrometer?

A

They are mostly exhaled (minimally deposited in lungs)

65
Q

Is particle size for inhaled aerosols constant for a given preparation?

A

No, particle sized is polydiverse

This explains how a relatively small percentage (15-25%) of inhaled drug actually reaches its target site as most is either trapped in the oropharynx/trachea or exhaled

66
Q

That is the impact of inhalation speed on efficacy of inhalation therapy?

A
  • Rapid inhalation
    a. Increases the possibility of deposition by impaction in the oropharynx and upper large conducting airways
  • Slow, steady inhalation
    a. Increased number of particles that will penetrate the peripheral portions of the lung
  • Breath-holding
    a. Enables the particles to settle into airways under gravity (reduce loss by exhalation)
67
Q

Can breath-holding be overdone?

A

Yes, a 20 second breath hold after administration of an inhaled drug results in reduced efficacy compared to 10 second breath hold

Likely due to increased expiratory force after 20 seconds of holding breath in

68
Q

Review slide 78 for proper inhalation technique

A
69
Q

What are two factors pharmacists should consider when reccomending an inhaler device type?

A
  1. Patient-related (clinical factors included)
  2. Drug-related
70
Q

What are some important patient related factors considered when selecting inhaler device type?

A
  1. Patients age (12 years)
  2. Physical and cognitive ability (proper coordination)
  3. Inability to generate deep breath
  4. Patient preference
  5. Cost and reimbursement
  6. Portability (especially for rescue meds)
71
Q

What are some important drug-related factors considered when selecting inhaler device type?

A
  1. Availability of drug in more than one dosage form
  2. Combination products vs. separately
  3. Ease of use (treatment time, portability, cleaning, and maintanence)
  4. Good durability (withstand mishandling and cleaning procedures)
72
Q

What is Raoult’s Law?

A

Applies to liquefied gas systems

Can help determine partial vapour pressure of a specific component in a mixture given constant temperature

Pi = Pi* x Xi

Pi = partial pressure of component in the mixture (propellant)

Pi* = vapour pressure of the pure component

Xi = mole fraction of component

73
Q

What is the ideal gas law?

A

Describes the pressure of compressed gas aerosols

pV=nRT

p = pressure (N/m^3)
V = volume (m^3)

n = number of moles of gas
R = universal gas constant (8.314 J/K/mole)
T = temperature (*K)

74
Q

What are some factors that can affect MDI performance?

A
  1. Shaking before use
  2. Temperature
  3. Nozzle
  4. Timing between actuation
  5. Priming
  6. Patient characteristics
75
Q

How does not shaking before using an MDI affect its performance?

A

Decreases total and respirable dose by 25-35%

This is because the drug and propellant can separate over time, so shaking helps to mix the two components

76
Q

How does temperature affect MDI performance?

A

MDI use in very cold weather can decrease aerosol drug delivery

Ensure use between -20C and 20C for best delivery

77
Q

How does the nozzle affect MDI performance?

A

Inner diameter of the nozzel is inversely proportional to the amount of drug delivered to the patient (smaller diameters = increased amount of drug delivered)

78
Q

How does timing between two separate actuations affect MDI performance?

A

Rapid actuation of more than 2 puffs (increased turbulence and coalescense of particles which reduces drug delivery)

79
Q

How does priming affect MDI performance?

A

Improves product delivery

Duration between doses that demands priming is product specific (given in product monograph)

ex. Ventolin needs priming if not used for more than 5 days, Flovent needs priming if not used for at least 1 week

80
Q

How do patient characteristics affect MDI performance?

A

Age (differences in physiology) and technique of application can impact the efficacy of MDIs

PHAR 224 (6 decks)

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