Inhalation drug delivery Flashcards
benefits of inhaled medication
rapid avoids GIT avoids first pass lower doses needed accurate dose measurement small volumes tamperproof- child safety protection
inhaled drug delivery provides and alternate route of administration for:
For acute and breakthrough pain treatment
Where physical and/or chemical interactions with other medications must be avoided
When the drug exhibits variable or erratic pharmacokinetics when given orally
When critical to avoid gi degradation of the therapeutic agent, e.g., biologics, insulin
components of the upper respiratory tract?
buccal sublingual nasal pharynx upper larynx
point of the nasal cavity?
moisten and warm air
filter out large particles >15mm
nasal cavity filters particles..
> 15mm
epiglottis role?
covers entrance to airways when swallowing
components of the lower respiratory tract?
trachea
bronchi
bronchioles
alveoli
how big are alveoli?
<1mm
how many alveoli in the lungs?
30 million per lung
surface area of alveoli?
70m2
where can particles deposit in the respiratory tract?
anywhere
extent and loci of particle disposition is controlled by?
product characteristics
dry powder
liquid aerosol
what affects the extent and loci of particle distribution in dry powder inhalers?
particle diameter shape density charge surface chemistry
what affects the extent and loci of particle distribution in liquid aerosols?
droplet size
velocity
nature of propellant
anatomical and physiological characteristics that affectextent and loci of particle distribution molecules?
lung capacity
breathing patterns
geometry of respiratory tract
there’s _____ disposition in the peripheral regions of the lungs
less
why could you see some drug in the stomach with inhaled drugs?
some deposited in mouth which will be swallowed
explain inertial impaction?
momentum of particle renders it unable to follow the airflow in a curved airway so that it impacts on the wall-travels too fast so just hit the walls. Significant forward momentum.
explain gravitational sedimentation?
related to the residence time in an airway & terminal settling velocity, increased by holding breath. In the time between inhalation and exhalation.
explain brownian diffusion?
random collision of particle with airway wall; significant only for particles < 0.1 mm- smaller they are, the more likely they are to be deposited
brownian diffusion is only significant for particles _____
<0.1
for brownian diffusion, the smaller they are the …..
more likely they are to be deposited
explain electrostatic attraction
charge on particle induces opposite charge on airway wall and accelerates particle into wall by attraction. Need to be travelling travelling quite slowly and close to the wall. By the time this happens, usually one of the other has happened
what are the circumstances for electrostatic attraction?
needs to be travelling quicte slowly
why is electrostatic attraction rarer than the others
as its slow so by the time it could happen, one of the other dispositions have occurred
explain interception
particle size approaches airway diameter. Only for very asymmetric and needle like particles. Can be tangled up like straw and get trapped
what disposition is most likely to happen to particles of an asymmetric and needle like structure?
interception
disposition by impaction and sedimentation are directly proportional to?
particle size
disposition by impaction and sedimentation are most significant for particles > than
1mm
in disposition by impact and sedimentation, the bigger the particle the….
more likely it will impact as it will be going quicker (impaction) and will sediment faster (gravitational)
desposition by infusion is ______ proportional to particle size. this means?
inversely
the smaller the size, the more diffusion
in traditional delivery devices, desposition is achieved primarily through which 2 methods?
impaction
sedimentation
for particles <10mm ____% of dose is not deposited. meaning?
80-90%
breathed out or swallowed
how can you improve disposition of inhalers with small molecules?
emit at lower velocities
emitting small particles at lower velocities achieves >___% disposition in the airways
30
what inhalation devices are good for the upper respiratory tract?
sprays
prssurised metered dose inhales use ______ based propellants
solvent- no longer cfcs
superfine particle inhalers are used for….
what do they produce
small airway disease
produce very small aerosol particles
what do superfine particle inhalers use as a propellant
hfas
explain nebulisers
drug dispersed in polar solvent- usually water
dry powder inhalers are replacing? why?
pressurised metered dose inhalers
no solvent propellant so no environmental issues
dry powder inhaler mechanism of drug delivery?
dry powder fluidises when patient inhales
drug shears from larger particles and penetrates deeper into the lungs
how does drug penetrate deeper into the lungs with dry powder inhalers?
drug shears from larger particles
3 uses for nasal sprays?
hay fever
sinusitis- steroids
decongestents
what do some sprays use now- more modern
metered dose pump
how do metered dose sprays work- from pressing the actuator?
releases the drug
when it returns to normal position, more drug is drawn up to replenish the supplies
vianase uses ______ technology. how does it give controlled particle dispersion
kurve
uses electronic atomiser to give controlled particle dispersion (with narrow size range: 10 – 30 mm); minimises pulmonary and gi deposition
what is vianase size range?
10-30mm
options uses _____ flow.
bidirectional flow
how does optinose work?
exploiting the blow reflex
to ensure large particles go to the nasal mucosa and prevent smaller particles going down into the lungs
blow into the mouth piece, the soft pallet closes which shuts the nasal cavity off to the airway
pMDI’s use a _____ propellent
liquid
what type of thing do pMDIs create?
fast moving micro-fine suspensions
how do the valves operate in pMDIs?
simultaneously to inhalation
manually operated or breath actuated
excipients in pMDIs?
: co-solvent (ethanol), inverse micelles, or liposomes to enhance solubility of surfactant propellants; surfactants (e.g., lecithin, oleic acid),
to adsorb to particles & prevent agglomeration (shake before use); menthol, flavouring; ascorbic acid, antioxidant; phenylethanol, preservative
patient advice with pMDIs?
shake before use
why are small airway diseases inadequately treated using traditional inhalers?
as the airways are smaller
airflow limitation
most particles generated in traditional pMDIs and DPIs deposit in …
the upper airways by sedimentation and impaction
small particle aerosols can be used to treat?
COPD
asthma
small particle aerosols can decrease the dose of?
corticosteroids needed
nebulisers only delivery ___% of nebuliser drug
13
how do traditional (air jet) nebulisers work?
compressed air or oxygen exits a narrow orifice at high velocity, creating negative pressure which draws liquid to top of tube, where it is aerosolised, giving droplets > 40 mm; very large droplets removed through impaction on bends in the equipment
what sized particles are produced by traditional air jet nebulisers
> 40mm
very large
issue with the equipment of traditional air jet nebulisers?
40mm very large droplets
removed by impaction on beds of the equipment
how do ultrasonic nebulisers work?
piezoelectric transducers used to focus (1- 3 mhz) ultrasound waves in liquid, with intense agitation at the focus to disperse the liquid and form aerosol
how do vibrating mesh ultrasonic nebulisers work?
alternating current causes piezo crystal to expand and contract rapidly, pulling mesh into liquid and then thrusting forward to create a monodisperse aerosol of superfine droplets (virtually all of which is appropriate for inhalation) these are much smaller and better for use
DPIs are _____ ______ _______ devices
passive breath dispersing
what type of inhalation is needed with DPIs?
quick
strong
deep
how are the drug particles delivered in DPIs?
small drug particles adhered to larger carrier particles – separated by sheer with large particles then being deposited in the oropharynx, and the smaller (drug) particles going down to the lower airways
how would active DPIs work?
examples?
- not commercial use yet
use an internal power source to aerosolize the powder; spirostm, uses a battery-powered motor, oriel, uses a piezoelectric polymer
carriers in DPI?
lactose or drug crystals
examples where drug crystals are used in DPI?
pulmicort (budenoside)
turbuhaler (az)
how are DPIs micronised?
by jet, pin or ball milling
or
spray drying or use of supercritical fluid
drug particles still attached to carrier in DPIs will be deposited?
smaller drug particles?
in the oropharyngeal area
into the lungs
efficient alveolar delivery of particles with aerodynamic diameters of?
1-5mm
what does aerodynamic diameter describe?
the dynamic behaviour of a particle relating to gravitational settling and inertial impaction
aerodynamic diameter determines what?
where the particles deposit
aerodynamic diameter can be increased by?
decreasing size
decreasing density
increasing shape factor
TF: a more assymetric/ needle like particle is more aerodynamic
true
if X>1 the aerodynamic diameter is?
less
elongated
if X=1 then what are the particles like?
more spiracle
if density is less then the D(ae) becomes ____
lower
aerodynamic diameter equation?
D(ae)= D(eq) (square root of:)Pp/ PpX
D(ae)= Aerodynamic diameter D(eq)= GEOMETRIC SIZE P(p)= density X= shape factor
