Routes of administration: inhaled Flashcards
Describe the features of the lung that make it good for drug absorption.
- Offers a large surface area
- Highly vascular surface promotes rapid absorption and onset of action
- The air-blood barrier is thinner compared to barriers in the intestine and other mucosal routes
Why is the inhalation route frequently used?
- For local delivery of drugs to the lungs for the treatment or prophylaxis of pulmonary diseases
- Administering a drug at its site of action can result in a
rapid onset of action. - Allows smaller doses to be used thus
reducing side effects. - But it can also be used to delivery
drug systemically.
What are the advantages of the inhalation route?
- Smaller doses compared to oral and parenteral routes:
– Reducing systemic side effects.
– Reducing drug costs.
– E.g. salbutamol requires 4mg orally vs 200μg via
inhalation. - Rapid absorption lead to fast onset of action.
- Avoids harsh GI environment thus minimises chemical
and enzymatic drug degradation. - Avoids GI upset.
- Avoids hepatic first-pass metabolism.
What are the disadvantages of the inhalation route?
- Requires complex delivery devices – high costs.
- Aerosol devices can be difficult to use, even for adults.
- Reproducibility of dose delivery is low due to various factors
e.g. incorrect use of device, lung capacity, breathing pattern. - Drug absorption may be limited by the mucus layer.
- Mucociliary clearance reduces the retention time of drugs
within the lungs – not suited for long-acting formulations. - Oropharyngeal deposition may give rise to local side effects.
Describe inhalation aerosols.
- A two phase system of solid particles or liquid droplets dispersed in the air
State the fate of particles in the airways.
Deposition > Dissolution > Absorption
State the patient factors affecting particle deposition.
Lung physiology e.g. lung capacity
Breathing patterns
Co-ordiantion of aerosol generation with inspiration
- Breath holding
Explain how breathing patterns affects particle deposition.
– The larger the inhaled volume, the greater the peripheral
distribution of particles.
– Increasing inhalation flow rate enhances impaction in
upper airway.
Explain how breath holding affects particle deposition.
– Breath holding after inhalation enhances deposition by sedimentation and diffusion.
State the physiochemical factors affecting drug deposition.
- the aerodynamic size of the drug particle
- Shape and physical stability of particles also affect deposition to lesser extent
What are the three main mechanisms responsible for drug deposition?
– Inertial impaction,
– Gravitational sedimentation,
– Brownian diffusion.
Describe inertial impaction.
- Particles within the air stream having high momentum will impact on the airway’s walls rather than following the changing air flow
Describe gravitational sedimentation.
- Sedimentation is dependent on particle size and density
and residence time in the airways - Occur in the small airways and alveoli, where the
velocity is much lower.
Describe brownian diffusion.
- Small particles <1 μm are bombarded by random gas
molecules and produce Brownian motion. This results in particle collision with the airway walls. - Common in regions where airflow is very low e.g. alveoli.
Describe the effect of particle size on deposition.
- Larger particles (i.e.> 5 μm) mostly deposit in
the upper airways by inertial impaction. - Particles 1-5 um mostly deposit in the lower
airways by gravitational sedimentation. - Particles <1 μm mostly deposit in the lower
airways by Brownian motion.
What is the optimum particle size range?
1-5 micrometres
Describe drugs in the mucus barrier.
- An aerosolised drug powder must first dissolve in the
mucus layer before absorption. - Dissolution can be the rate-limiting step, especially for
poorly soluble drugs. - Once in solution, the drug will diffuse through the
mucus layer and enter the aqueous environment of the
epithelial lining liquid.
What is meant by mucociliary clearance.
- Mucus layer constantly being propelled along the airways by rhythmic beating of cilia on epithelial cells
When can drug absorption take place?
- If dissolution is faster than clearance
Describe the absorption of hydrophobic materials.
- absorbed at a rate dependent on the oil/water partition coefficients i.e LogP
Describe the absorption of hydrophilic compounds.
- Poorly absorbed through membrane pores at rates inversely proportional to molecular size
- Unionised form is better absorbed than ionised form
Which form of drug is better absorbed?
Unionised from
What can rate of absorption be influenced by?
The overall drug formulation
