Inhalation formulations

Question 1

What cillia is the upper respiratory tract (trachea, nasopharynx and bronchi) lined with and what is its function

Answer 1

Cilliated columnar epithelium cells ‘beat’ upwards moving particles trapped in mucous away from the lungs.

Question 2

What kind of cillia are the bronchioles lined with

Answer 2

The bronchioles are lined with cilliated cuboidal cells

Question 3

Describe what lines the alveolar region and their functions

Answer 3

Alveolar walls - Lined with a film of phospholipid that acts as a pulmonary surfactant.

Alveolar ducts - lined with a single layer of squamous cells that enhance gas permeability to the capillaries.

Question 4

What drug metabolyzing enzymes are present in the lungs

Answer 4

• CYP450
• Esterase
• Protease
• Peptidase

Question 5

What are some of the complications that drug particles encounter along the way in the lungs

Answer 5

If they are larger than 5μm in diameter…
* Trapped in mucous
* Mucocillary clearance -> ingested creating unwanted adverse effects

Additionally alveolar macrophages may engluf and degrade drug particles.

Fine drug particles are also prone to being exhaled if they do not sediment.

Question 6

what is the ideal particle size for drug particles in the lungs

Answer 6

1-5μm in diameter

Question 7

What is inertial impaction

Answer 7

Particles with a high velocity and size will have an increased probability of impaction. This is the particles hitting the airway walls at turns and becoming trapped in mucous.

Question 8

What is Brownian diffusion

Answer 8

When small fine particles reach the alveolar region, sediment and then diffuse into the circulation

Question 9

What inhaled devices use propellant

Answer 9

MDIs

Question 10

What is propellant and its function

Answer 10

Liquidifed gas that acts as a solvent for the drug to dissolve in. It…
* Provides cosntant pressure levels
* Maintains stability

Question 11

What are types of propellants and their differences

Answer 11

Chlorofluorocarbons and Hydrofluorocarbons.
* CFC was found to be ozone-depleting and so is not used as much due to its negative effects on the environment.
* HCH has no reaction with the ozone layer and is miscible with water and alcohol. However it is not a good solvent for surfactant.

Question 12

What are the advantages and disadvantages of using MDIs over other inhalatory devices

Answer 12

Advantages
* Portable
* Non-breathing activated
* Uniform drug distribution within the metering chamber

Disadvantages
* Requires correct actuation and inhalation coordination
* Oropharyngeal deposition

Question 13

What are spacers and what are their use

Answer 13

Spacers are a plastic tube that fit onto the mouthpiece of an inhaler. It increase the distance between the canister and the patients mouth ∴ provides more time to coordinate breathing with actuation.

Usually required for children and patients with poor technique.

Question 14

Advantages/disadvantages of spacers

Answer 14

Advantages
* Provides an alternative for people with poor technique
* Used for children
* Large particles often become trapped insde the valve = Less inertial impaction = Less GI indigestion = Less side effects

Disadvantages
* Requires frequent cleaning
* Inconvienient portability but portable
* Only applicable with CFC propellant

Question 15

What are the advantages of Respimat soft mist inhaler (SMI)

Answer 15

Advantages
* Generates very fine particles
* Slow velocity of mist = More time to coordinate
* Spacer unnecessary
* Deposition in the lower repiratory tract is double compared to MDI = Increased therapeutic effect
* Used for low-dose drugs

Question 16

What are co-solvents and their use

Answer 16

• Increase solubility
• Can be used as a wetting agent
• Maintains valve function
• Reduces friction caused by actuation

Examples: Ethanol, PEG 1000

Question 17

What are dry powder inhalers and their advantages/disadvantages

Answer 17

Advantages
* More stable
* Low velocity = Less inertial impaction
* No coordination of the actuation and inhalation required
∴ great for children, elderly and arthritic patients
* Portable & compact
* Propellant not required
* Spacer not required

Disadvantages
* Efficancy is flow dependent

Question 18

What are the different type of dry powder formulations

Answer 18

• Micronised drug
• Loose agglomerates
  Secondary particle formed by powder resulting in better flow
• Carrier blend
  Drug particles are suspended in lactose and separate once entering the pulmonary region

Question 19

What are the advantages/disadvantages of nebulisers

Answer 19

Advantages
* Deliver more accurate dose
* Breathing coordination not required
* Large doses can be administered

Disadvantages
* Not portable (usually administered in the hospital)
* Requires salt to maintain tonicity
* Requires sterile aqueous solution
* Stabilisers required for labile molecules

Question 20

What factors impact dose delivery for nebulisers

Answer 20

Viscosity -> Lower is better
* Lower viscosity means it is easier to generate the aerosol and it doesn’t require as much pressure

Surface tension -> Lower is better
* Easier to atomise and therefore easier to generate aerosols from solution

Question 21

What are the suitable size range for good lung deposition of the inhaled medication?

Answer 21

1-5μm

Question 22

What is the difference between air jet nebulisers and ultrasonic nebulisers

Answer 22

Air jet nebulisers cool down the liquid through its mechanism whereas ultrasonic heats up the liquid

Question 23

What are the different processes that impact particle deposition in the lungs

Answer 23

• Inertial impaction
• Gravitational settling
• Electrostatic interactions
• Brownian diffusion

Question 24

What is brownian diffusion

Answer 24

The unpredicted motion of small particles in the lungs due to the easy of influence by inhalation-exhalation and the collision of other particles. This process describes a poor drug deposition in the lower lungs due to too small particle size.

Question 25

What is gravitation settling

Answer 25

The settling of fine particles due to gravity. This most commonly occurs in the lower airways and alveolar cavities.

Question 26

What can impact gravitation settling and particle motion

Answer 26

• Air viscosity - A more dense air will result in slower particle movement ∴ slower settling speed.
• Aerodynamic diameter - A larger size and weight of the particle will result in a faster settling speed
• Humidity - Can cause partial dissolution at particle surface of hydrophilic particles ∴ increases particle size and aerodynamic diameter

Question 27

Why do we ask patients to hold their breaths for 10 seconds when using an inhalatory device

Answer 27

To give particles time to settle and sediment in the lower lungs before exhalation occurs. This…
* Prevents immediate exhalation of drug particles
* Increases drug amount that settles ∴ increases therapeutic effect

Question 28

How does smoking affect the lungs

Answer 28

Chemical particles damage cillia ∴ cilia lose muco-cillary clearance function

Chemical particles: Hydrogen cyanide, formaldehyde, Phenols, Ammonia

Question 29

How do you calculate the respirable fraction from an andersen test graph

Answer 29

Extrapolate the cumulative percentage of drug values of 1μm and 5μm. Find the value that represents that range by substracting the 1μm from 5μm percentage. (E.g. 88%-40% = 48% of the dose is respirable)