W22 Pulmonary Drug Delivery Flashcards
What is the respiratory tract broken up into
3 parts
upper airways
central conducting airways
respiratory peripheral pulmonary airways
what is the role of the lung
organ of external respiration in which oxygen and carbon dioxide is exchanged between blood and inhaled air
how big is the surface area of the lungs
140 metre sqaured
why does the lung have a large surface area
to help with exchange of carbon dioxide
what are some advantages of pulmonary drug delivery
can be used to treat airways disease
pulmonary administration results in rapid on set of action
smaller doses can be administered locally compared to delivery by the oral or parenteral routes
route is useful when a drug has poor absorbed orally.
how can we deliver a drug to the airways
must be presented as an aerosol except for medical gases
what is an aerosol
defined as a two phase system of solid particles or liquid droplets dispersed in air or other gaseous phase.
what is needed to ensure stability for an aerosol
small size
what is the aerodynamic particle diameter
is the diameter of a sphere with a density of 1g/cm3 that has the same aerodynamic behaviour as the particle which shall be characterized.
what mechanisms are responsible for particulate deposition
impaction
gravitational sedimentation
diffusion
What will particles settling under gravity
it will attain a constant terminal settling velocity
what is terminal settling velocity equal too
(Particle density x standard gravity x particle diameter)/ 18 x air viscosity
what is inertial impaction
dominant deposition mechanism for particle > 1 uM in the upper tracheobronchial regions. A particle with a large momentum may be unable to follow the changing direction inpired air as it passes the bifurcations and as a result will colide with the airway walls
impaction is proportional
Gravity x Raidus airway
What is the particle deposition affected by
diffusion increases as the particle size decreases
what are 4 factors that affect the physiological factors affecting particle deposition in the airway
lung morphology
oral versus nasal breathing
inspiratory flow rate
breath holding
what is lung morphology
to travel down the airways, the drug particles must pass through a successive series branch tubes of constantly decreasing size
what is oral versus nasal breathing
during normal nose breathing the majority of inhaled evironmental particles are deposited in the nose and pharynx. For pulmonary delivery the aerosols are inhaled via the mouth
what is inspiratory flow rate
increasing inspiratory flow rate will enhance deposition by impaction in the large airways
what breath holding
breath holding after inhalation enhanes the deposition of particles by sedimentation and diffusion.
what pharmaceutical factors affect aerosol deposition
aerosol velocity
size and size distribution
shape
density
physical stability
what must a drug given as an aerosol powder do
first needs to dissolve through the mucus layer. Dissolution may be a rate determining step, especially for poorly soluble drugs
what is the rate of diffusion of an aerosolised powder dependent on
size of mucus layer
mucus viscosity
molecular size of drug
interactions between drug + mucus
what are the advantages of pulmonary drug delivery for locally
dose needed to produce a pharmacological effect can be reduced compared to oral dosing
low concentration in the systemic circulation so reduced side effects
rapid onset
avoidance of GI upset
avoidance of intestinal and hepatic first pass metabolism
what are the advantages of pulmonary drug delivery for systemically acting drugs
large surface area for absorption
permeability of the lung membranes towards many compounds is higher than that of small intestine and other mucosal routes
highly vascular surface promotes rapid absorption and onset of action
less hostile environment than the oral route
what are the disadvantages for delivery of systemically acting drugs
complex delivery devices are regulated to target drugs to the airways and these devices may be inefficient
aersol devices can be difficult to use
various factors may affect the reproducibility of drug delivery
drug absorption may be limited due to mucus
mucociliary clearance reduces the retention time of drugs within the lungs
what are 3 examples of current technologies that use the pulmonary route
pressurised metered dose
dry powder inhalers
nebulisers
what is the most common inhalation drug delivery device
pMDI
what is contained within a pMDI
drug dissolved in liquid propellant together with some other excipients including surfactants and preserved in a pressurized canister fitted with a metering valve.
what happens when the drug goes to be released in a pMDI
when released from the canister the formulation undergoes volume expansion in the passage within the valve and forms a mixture of gas and liquid before discharge
what is the pMDI composed of
container
metering valve
elastomeric seal
actuator
what are 4 examples of propellant
CFCL3
CCL2F2
CCIF2CCIF2
CF3CH2F
what are the advantages of pMDI
unit dosin
cheap
what are the disadvantages of pMDI
use of CFCs
aerosol velocity
co-ordination difficulties
what are the advantages of DPI
no coordination problems
lower drug loss by impaction
what are the disadvantages of DPI
high inspiratory effort
may be required coughing reflex, less convenient than pMDI
what are the advantages of a Nebuliser
generates small particles with higher delivery capacity
no coordination required
what are the disadvantages of a nebuliser
inconvenient
long inhalation times
poor dose control
expensive
lack of portability.
