P5 & P6: Nasal & Otic Drug Delivery Flashcards
why is nasal drug administration useful
avoids first-pass metabolism, drugs sensitive to intestinal metabolism, acid-sensitive drugs, polar compounds with poor oral absorption
how are drugs absorbed in the nose
small, lipophilic drugs can diffuse through nasal epithelium and enter systemic circulation with bioavailabilities up to 100%
what is the main function of the nose
air conditioning
what are the physiological features of the nose
temp= 20-55degreesC humidity= 97-98% filtration vol= 20ml surface area= 150cm2 rich mucosal blood supply high air turbulence
what are the cellular features of nasal epithelium
ciliated cells that move slightly out of phase with neighbours
pseudo-stratified columnar epithelium, large surface area due to microvilli
protective mucous layer and colia for clearance
what is the function of mucous
traps particulates (including bacteria and viruses)
acts as a physical barrier that drugs must traverse before being absorbed
may actually bind to drugs via electrostatic interactions or hydrogen bonding, preventing diffusion
contains enzymes that degrade drugs
how are aerosols or powders deposited in the nasal cavity
distributed according to particle size
how are liquid drops deposited in the nasal cavity
spread throughout the cavity
what happens to particles deposited on the ciliated regions during mucociliary clearance
cleared immediately
what happens to particles on non-ciliated regions during mucociliary clearance
move more slowly
what happens to particles deposited on nasopharyngeal regions in mucociliary clearance
swallowed at once and not available
why are nasal sprays more efficient than drops
more deposition of the spray on non-ciliated regions
what are some examples of drugs used to treat congestion
ephedrine HCl
pseudoephidrine HCl
what are some examples of drugs used to treat allergy
beclomethasone dipropionate
sodium cromoglycate
levocabastine
what are some examples of drug used to treat infection
mupirocin
chlorhexidine
what are the key considerations when making nasal formulations
provides pharmocological activity, no effect on cleansing action of cilia on the nasal mucosa, avoidance of non-aqueous formulations
how is pH controlled in nasal formulations
buffered between 5.5 and 6.5 to preserve nasal function
pH affects drug’s ionisation state and the absorption rate
what buffers are used in nasal formulation
citrate, phosphate
what considerations are made for vehicles used in nasal formulations
nasal formulations are aqueous so non-aqueous solvents may interfere with ciliary function
small amounts of co-solvents may be used to improve drug solubility
why are viscosity modifying agents are used in nasal formulations
viscosity affects ease of administration and retention of formulation on mucosa
modified with hydrophilic polymer so consistency is similar to mucous
what preservatives can be used in nasal formulations
chlorobutanol, parabens, benzalkonium chloride, thimerosal
why are antioxidants used in nasal formulations
enhance chemical stability of drugs prone to oxidative degredation
water-soluble anti-oxidants are preferred
what are the advantages of nasal administration for vaccinations
needle-free so better patient compliance, non-invasive, small antigenic dose, induction of systemic and mucosal immunity, immunity at primary and distal mucosal sites
what are the disadvantages of nasal administration for vaccinations
rapid clearance, inefficient uptake, lack of human compatible mucosal adjuvant
what is Fluenz Tetra nasal spray suspension
influenza vaccine (live attenuated, nasal) used in children and adolescents contra-indicated if allergic to gelatin, gentamycin, egg, compromised immune system or if using aspirin; administered nasally
what are the common side effects of the Fluenz Tetra nasal spray suspension
runny or stuffy nose, reduced appetite, weakness, headache, fever, muscle aches
what are the six steps of using the Fluenz Tetra nasal spray suspension
- check expiry date
- prepare the applicator by removing rubber tip
- position the applicator with pt in upright position & tip inside nostril
- depress the plunger with a single motion as rapidly as possible until the dose-divider clip prevents you from going further
- remove dose-divider clip, pinch and remove dose-divider clip for administration into the other nostril
- spray into the other nostril
how are drugs delivered to the brain after nasal administration
via olfactory neurones
how do drugs directly enter the brain
via paracellular diffusion or axonal transport through olfactory nerves
what are the advantages of nasal drug delivery
large surface area, rich blood supply, low metabolic activity, accessibility, ease of administration, alternative when oral route not feasible
what are the disadvantages of nasal drug delivery
mucociliary clearance gives low bioavailability, mucous barrier means slow diffusion and binding, metabolic activity to peptides/proteins, only potent drugs for systemic delivery, poor reproducibility, adverse reactions
how can nasal drug delivery be improved
alter mucous layer, increase contact time with nasal epithelium, penetration enhancers
what is the ViNase delivery system
vortex disrupts normal air flow, nasal deposition maximised, residence time increased, lung deposition minimised
when is otic drug delivery used
blood-cochlear barrier exists (similar to BBB)
paediatric drugs include therapies for otitis externa, otitis media and ear wax removal
small volume generally used as excess is lost out of ear passage
what are the different types of inner ear drug delivery
intra-tympanic, intra-cochlear
what does inner ear drug delivery require
intra-tympanic
high drug concentration driving diffusion into scala tympani, across round window membrane (RMW) from middle ear
variable RMW limits dosing accuracy
drug delivery to middle ear can be lost into pharynx via Eustachian tube
what are the typical formulations for inner ear drug delivery
(intra-tympanic)
biodegradable polymers, hydrogels, nanoparticles, micro-catheters, osmotic pumps
delivery systems use local triggers to stimulate drug release
what does inner ear drug delivery involve (intra-cochlear)
direct intra-cochlear drug delivery involves placement of drugs within cochlear peri-lymphatic spaces
molecules perfused into a peri-lymph compartment have direct access to cells of inner ear
what are the methods of delivery to the inner ear (intra-cochlear)
micro and osmotic pumps
development of novel implantable delivery devices
what are some examples of otic formulations
solutions (sterile, isotonic, acidic, co-solvents, thickened, drops, sprays, lipophilic vehicles for earwax removal)
gels used to prolong delivery
foams aid drug retention in ear and facilitate administration
micro-wick technology draws medicaiton to RWM for intra-tympanic delivery
osmotic pumps offer controlled drug delivery but require surgical implantation
cochlear implants
