RESP - D. NASAL AND AURAL DRUG DELIVERY-COVERED Flashcards
local action of drugs administered to nasal cavity
- lower doses
- reduced side effects but also get a fraction of dose into systemic circulation as nasal cavity is very permeable
what are the 5 regions of the nose
- vestibule (nasal hairs present)
- atrium
- resp region with inferior, middle and superior turbinates
- olfactory region
- nasopharynx
what are turbinates
curled spongy bones that protrude in nasal passages
what do turbinates do
- create air turbulences which have a role in:
1. air humidification and heating: increase contact time between air and mucosa, cold air reaches body temp before it progresses down resp tract so more comfortable
2. filtration of air particles by inertial impaction
3. olfaction: directs other substances to olfactory region - increase SA for absorption
respiratory epithelium
pseudostratified columnar
- ciliated cells
- non-ciliated cells
- goblet cells
- basal cells
covered by mucus
similar to tracheal/bronchial epithelium
what is mucus composed of
- water (95%), salts, glycoproteins - mucins, enzymes, immunoglobulins, lysozyme
- pH 5.5-6.5
- biphasic
1. low viscosity layer in contact with epithelium to allow beating of cilia
2. upper, viscous layer which prevents evaporation from epithelium
role of mucus
- protects epithelium from dehydration, micro-organisms, inhaled particles
- particles trapped in mucus, moved towards nasopharynx by cilia and swallowed (mucociliary clearance) - destroyed in GIT
- 15-20min then eliminated from nasal cavity
why is drug absorption from nasal cavity high
mainly from respiratory region
- LSA
- high vascularisation
- prolonged contact time (turbinates)
- directly into systemic circulation from nasal cavity
- high inter-patient variability
mechanisms by which drug absorption in nasal cavity occurs
- passive diffusion (trans/para cellular)
- transcytosis
- receptor-mediated transport
*non-polar and polar (inc. peptides) drugs
advantages of nasal delivery for a systemic action
- easy access
- non-invasive, painless
- avoids GIT (low bioavailability drug can be given)
- rapid absorption and onset of action (anti migraine)
- easy formulation
*avoids 1st pass metabolism but high levels of metabolising enzymes in nose
limitations of nasal drug delivery
- small cavity so only 100microlitres can be given
- drug must be highly soluble in water
- drug must be potent
- cleared in 15 minutes by mucociliary clearance so needs to cross epithelium quickly (hydrophobic drugs more effective)
- mucus can be a barrier as some drugs bind to it
- high levels of cytochrome P450 and proteases
- low absorption if MW >1kDA
- nasal irritations
- taste/smell issues as fraction of drug ends up in mouth
nasal delivery of peptides
- avoidance of frequent injections
- short peptides as if too big won’t cross nasal epithelium
- low bioavailability as:
low absorption due to high MW
enzymatic degradation in nose by peptidases
high doses need to be given - cheaper than injection
Nafarelin, Calcitonin
creams and ointments
- topical delivery around nostrils
Bactroban
nasal drops
- solutions or suspension by dropper bottle
- dose not accurate
- good spread
- head down and back curved
Otrivin
nasal sprays
- aerosols of droplets or solid particles >50microns (or enter lung)
- deposit by inertial impaction
- better control of dose
- penetrate deeper in nasal cavity: direct spray to back of nose, not near partition
- liquid sprays: less irritation but contain peptides so not as stable) - store in fridge
