Nasal and otic drug delivery

Question 1

Advantages of nasal systemic delivery

Answer 1

Avoids 1st pass effect and intestinal metabolism
Acid sensitive drugs can be used
Polar compounds with poor absorption can be used
Small lipophilic drugs can be used
Easy to use

Question 2

Functions of the nose

Answer 2

Major: AC

• temperature
• humidity
• filtration

Minor: Smell

Question 3

Structural features of nose

Answer 3

Volume: 20ml
Surface area: 150cm cubed
Rich blood supply
Lots of turbulence

Question 4

Nasal epithelium: Ciliated cells

Answer 4

200 cilia per cell

Movement slightly out of phase with neighbors

Question 5

Nasal epithelium: Pseudostratified columnar epithelium

Answer 5

Has a large surface area due to microvilli

Protective mucus layer and cilia for clearance

Question 6

Mucus consists of…

Answer 6

90-95% water
1-2% salts
3% lipids
0.5-5% proteins

Question 7

Functions of mucus

Answer 7

Traps particulates
Physical barrier between epithelium and outside
Can bind to drugs preventing diffuse of drugs
Contains enzymes which may degrade drugs

Question 8

Clearance in the nose

Answer 8

If particles are deposited on:
Ciliated regions: quick clearance
Non ciliated: slower clearance
Nasopharyngeal region: gets swallowed and therefore not available

Mucus clearance ~ 10-20mins
Spray usually better than drops unless v. rapid absorption

Question 9

How much of the drug delivered nasally is deposited in lungs?

Answer 9

None.

The major is in nose, pharynx and stomach

Question 10

Effect of molecular weight on absorption

Answer 10

Small MW=well absorbed
Absorption >500= much worse
MW>1000= 1-3% at most

Question 11

Nasal formulations

Answer 11

Aqueous based so as not to effect clearance of cilia

Generally used to treat congesion, allergic rhinitis and infection

Question 12

Requirements for nasal formulation

Answer 12

pH between 5.5 and 6.5
Must be isotonic
Viscosity should be similar to that of mucous
Must has preservative as it is multidose
Antioxidants for those drugs at risk of degradation

Question 13

Delivery to brain through nose

Answer 13

Olfactory epithelium is one small area (4 cm2) where BBB is not present

Drugs can enter via paracellular paths/axonal paths through olfactory nerves

Question 14

Ways to improve nasal delivery

Answer 14

Surfactants/bile salts reduce viscosity of mucus which can increase drug absorption

Use mucoadhesives to increase contact time with epithelium

Primary purpose is to increase uptake of peptides

Question 15

ViaNase and Optinose

Answer 15

Devices that alter turbulence in nose thereby increasing the dose delivered and minimising lung deposition

Question 16

Anatomy of ear: external auditory canal

Answer 16

Around 23.5 mm in length

4.8-9.3mm wide

Question 17

Anatomy of ear: Middle ear

Answer 17

(Not to be confused with my home, middle earth)
Tympanic membrane separates external and middle ear

The cavity is small and contains 3 auditory ossicles

Infections can spread here

Question 18

Anatomy of ear: Inner ear (Labyrinth)

Answer 18

Contains cochlea (hearing) and vestibular system (balance)

Pretty inaccessible, difficult to pop in drugs (also due to blood-cochlea barrier)

Question 19

Inner ear drug delivery: intra tympanic

Answer 19

High amounts of drug must diffuse into scali tympani across round window membrane from middle ear

RWM permeability is variable so drug accuracy not very good

Drug can also be lost into pharynx via eustachian tube

Question 20

Inner ear drug delivery: intra cochlear

Answer 20

Can implant drugs directly into cochlear per-ilymphatic spaces

Such drugs have direct access to cells of inner ear

Delivered via micro/osmotic pumps