P5 & P6: Nasal & Otic Drug Delivery

Question 1

why is nasal drug administration useful

Answer 1

avoids first-pass metabolism, drugs sensitive to intestinal metabolism, acid-sensitive drugs, polar compounds with poor oral absorption

Question 2

how are drugs absorbed in the nose

Answer 2

small, lipophilic drugs can diffuse through nasal epithelium and enter systemic circulation with bioavailabilities up to 100%

Question 3

what is the main function of the nose

Answer 3

air conditioning

Question 4

what are the physiological features of the nose

Answer 4

temp= 20-55degreesC
humidity= 97-98%
filtration
vol= 20ml
surface area= 150cm2
rich mucosal blood supply
high air turbulence

Question 5

what are the cellular features of nasal epithelium

Answer 5

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

Question 6

what is the function of mucous

Answer 6

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

Question 7

how are aerosols or powders deposited in the nasal cavity

Answer 7

distributed according to particle size

Question 8

how are liquid drops deposited in the nasal cavity

Answer 8

spread throughout the cavity

Question 9

what happens to particles deposited on the ciliated regions during mucociliary clearance

Answer 9

cleared immediately

Question 10

what happens to particles on non-ciliated regions during mucociliary clearance

Answer 10

move more slowly

Question 11

what happens to particles deposited on nasopharyngeal regions in mucociliary clearance

Answer 11

swallowed at once and not available

Question 12

why are nasal sprays more efficient than drops

Answer 12

more deposition of the spray on non-ciliated regions

Question 13

what are some examples of drugs used to treat congestion

Answer 13

ephedrine HCl

pseudoephidrine HCl

Question 14

what are some examples of drugs used to treat allergy

Answer 14

beclomethasone dipropionate
sodium cromoglycate
levocabastine

Question 15

what are some examples of drug used to treat infection

Answer 15

mupirocin

chlorhexidine

Question 16

what are the key considerations when making nasal formulations

Answer 16

provides pharmocological activity, no effect on cleansing action of cilia on the nasal mucosa, avoidance of non-aqueous formulations

Question 17

how is pH controlled in nasal formulations

Answer 17

buffered between 5.5 and 6.5 to preserve nasal function

pH affects drug’s ionisation state and the absorption rate

Question 18

what buffers are used in nasal formulation

Answer 18

citrate, phosphate

Question 19

what considerations are made for vehicles used in nasal formulations

Answer 19

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

Question 20

why are viscosity modifying agents are used in nasal formulations

Answer 20

viscosity affects ease of administration and retention of formulation on mucosa
modified with hydrophilic polymer so consistency is similar to mucous

Question 21

what preservatives can be used in nasal formulations

Answer 21

chlorobutanol, parabens, benzalkonium chloride, thimerosal

Question 22

why are antioxidants used in nasal formulations

Answer 22

enhance chemical stability of drugs prone to oxidative degredation
water-soluble anti-oxidants are preferred

Question 23

what are the advantages of nasal administration for vaccinations

Answer 23

needle-free so better patient compliance, non-invasive, small antigenic dose, induction of systemic and mucosal immunity, immunity at primary and distal mucosal sites

Question 24

what are the disadvantages of nasal administration for vaccinations

Answer 24

rapid clearance, inefficient uptake, lack of human compatible mucosal adjuvant

Question 25

what is Fluenz Tetra nasal spray suspension

Answer 25

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

Question 26

what are the common side effects of the Fluenz Tetra nasal spray suspension

Answer 26

runny or stuffy nose, reduced appetite, weakness, headache, fever, muscle aches

Question 27

what are the six steps of using the Fluenz Tetra nasal spray suspension

Answer 27

1. check expiry date
2. prepare the applicator by removing rubber tip
3. position the applicator with pt in upright position & tip inside nostril
4. depress the plunger with a single motion as rapidly as possible until the dose-divider clip prevents you from going further
5. remove dose-divider clip, pinch and remove dose-divider clip for administration into the other nostril
6. spray into the other nostril

Question 28

how are drugs delivered to the brain after nasal administration

Answer 28

via olfactory neurones

Question 29

how do drugs directly enter the brain

Answer 29

via paracellular diffusion or axonal transport through olfactory nerves

Question 30

what are the advantages of nasal drug delivery

Answer 30

large surface area, rich blood supply, low metabolic activity, accessibility, ease of administration, alternative when oral route not feasible

Question 31

what are the disadvantages of nasal drug delivery

Answer 31

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

Question 32

how can nasal drug delivery be improved

Answer 32

alter mucous layer, increase contact time with nasal epithelium, penetration enhancers

Question 33

what is the ViNase delivery system

Answer 33

vortex disrupts normal air flow, nasal deposition maximised, residence time increased, lung deposition minimised

Question 34

when is otic drug delivery used

Answer 34

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

Question 35

what are the different types of inner ear drug delivery

Answer 35

intra-tympanic, intra-cochlear

Question 36

what does inner ear drug delivery require

intra-tympanic

Answer 36

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

Question 37

what are the typical formulations for inner ear drug delivery
(intra-tympanic)

Answer 37

biodegradable polymers, hydrogels, nanoparticles, micro-catheters, osmotic pumps
delivery systems use local triggers to stimulate drug release

Question 38

what does inner ear drug delivery involve (intra-cochlear)

Answer 38

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

Question 39

what are the methods of delivery to the inner ear (intra-cochlear)

Answer 39

micro and osmotic pumps

development of novel implantable delivery devices

Question 40

what are some examples of otic formulations

Answer 40

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