Inhalation formulations Flashcards
What cillia is the upper respiratory tract (trachea, nasopharynx and bronchi) lined with and what is its function
Cilliated columnar epithelium cells ‘beat’ upwards moving particles trapped in mucous away from the lungs.
What kind of cillia are the bronchioles lined with
The bronchioles are lined with cilliated cuboidal cells
Describe what lines the alveolar region and their functions
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.
What drug metabolyzing enzymes are present in the lungs
- CYP450
- Esterase
- Protease
- Peptidase
What are some of the complications that drug particles encounter along the way in the lungs
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.
what is the ideal particle size for drug particles in the lungs
1-5μm in diameter
What is inertial impaction
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.
What is Brownian diffusion
When small fine particles reach the alveolar region, sediment and then diffuse into the circulation
What inhaled devices use propellant
MDIs
What is propellant and its function
Liquidifed gas that acts as a solvent for the drug to dissolve in. It…
* Provides cosntant pressure levels
* Maintains stability
What are types of propellants and their differences
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.
What are the advantages and disadvantages of using MDIs over other inhalatory devices
Advantages
* Portable
* Non-breathing activated
* Uniform drug distribution within the metering chamber
Disadvantages
* Requires correct actuation and inhalation coordination
* Oropharyngeal deposition
What are spacers and what are their use
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.
Advantages/disadvantages of spacers
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
What are the advantages of Respimat soft mist inhaler (SMI)
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
What are co-solvents and their use
- Increase solubility
- Can be used as a wetting agent
- Maintains valve function
- Reduces friction caused by actuation
Examples: Ethanol, PEG 1000
What are dry powder inhalers and their advantages/disadvantages
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
What are the different type of dry powder formulations
- 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
What are the advantages/disadvantages of nebulisers
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
What factors impact dose delivery for nebulisers
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
What are the suitable size range for good lung deposition of the inhaled medication?
1-5μm
What is the difference between air jet nebulisers and ultrasonic nebulisers
Air jet nebulisers cool down the liquid through its mechanism whereas ultrasonic heats up the liquid
What are the different processes that impact particle deposition in the lungs
- Inertial impaction
- Gravitational settling
- Electrostatic interactions
- Brownian diffusion
What is brownian diffusion
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.
What is gravitation settling
The settling of fine particles due to gravity. This most commonly occurs in the lower airways and alveolar cavities.
What can impact gravitation settling and particle motion
- 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
Why do we ask patients to hold their breaths for 10 seconds when using an inhalatory device
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
How does smoking affect the lungs
Chemical particles damage cillia ∴ cilia lose muco-cillary clearance function
Chemical particles: Hydrogen cyanide, formaldehyde, Phenols, Ammonia
How do you calculate the respirable fraction from an andersen test graph
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)
