L9: ENT/dental delivery systems

Question 1

What is the anatomy of the ENT and oral passage?

Answer 1

Interconnected series of mucosal tissues
- Eardrums, nostrils, lips, oesosophagus (after this no longer mucosal)

Links ears, nose, tongue

Particulate matter is cleared by expulsion or swallowing

Question 2

Is the outer ear mucosal?

Answer 2

NO - epithelium, protected by cerumen (earwax)

Question 3

What are some indications for outer ear preparations?

Answer 3

Only for local use in outer ear

- Earwax removal, anti-infective, anti-inflammatory, analgesic

Question 4

What excipients are in outer ear solutions?

Answer 4

Water
Ethanol –> highly volatile & will evaporate quickly, taking excess fluid with it and leaving drug behind in the ear

More viscous solvents –> to allow drug to stay in ear canal for longer, but make it harder for earwax to come out –> depends on indication ie. antibiotics vs earwax removal

• Glycerin
• Propylene glycol

Question 5

What are the characteristics of the eardrum & what does it mean for some formulations?

Answer 5

Water-tight, air-tight barrier

• Eardrops cannot permeate through tissue
• Injections rarely performed, in operation setting
• -> Systemic/oral formulations most appropriate

Question 6

What are the paranasal sinuses?

Answer 6

Paired cavities connected to ENT system

Question 7

How to treat local infections?

Answer 7

NASAL IRRIGATION to treat locally

• Drain mucous from nasal/sinus passages (salt rinses)
• Can reach all connected sinuses & Eustachian tube

Question 8

Nasal mucosa - characteristics

Answer 8

Rich blood supply into systemic circuit

Access to nervous system –> can get straight into cerebrospinal fluid

Drugs delivery can be local, systemic, brain-targeted

Question 9

What is the relationship between mucous & mucosa?

Answer 9

Mucous

• Viscous aqueous discharge ON TOP of mucosal epithelial surfaces
• Drugs must be able to permeate through this & not be cleared out

Mucosa

• Epithelial surfaces COATED with mucous
• Important barrier function

Question 10

How can drugs deposit in the nose?

Answer 10

To ensure droplets remain in the nose & are not inhaled into the lungs (5-10 micrometre) –> particle size should be 30-120 micrometre

Question 11

How is drug droplet size controlled?

Answer 11

Vapour pressure –> higher = smaller size

Drug particle diameter –> aerosol diameter will also be larger since it has to coat drug particle

Actuator nozzle diameter (mesh bit)

Drug concentration –> increased size can aggregate & make ‘bigger’ particles

Question 12

Nasal delivery systems need to have properties of…

Answer 12

MUCOPENETRATION
- Ability to freely move around MUCOUS fluid

MUCOADHESION
- Ability to form intermolecular interactions and stick to MUCOSAL membrane

–> to prevent getting cleared by ciliary processes in the nose

Question 13

How is mucopenetration achieved?

Answer 13

Easier for small, uncharged particles

Question 14

How is mucoadhesion achieved? (what types of excipients must be contained?)

Answer 14

Effectively wet & spread around the mucosa

Interact with mucosal glycoproteins (so that mucoadhesion can take place)
- van der Waals preferred over ionic –> hydrophobic. fits with small uncharged properties of the particle in mucopenetration

eg. PEG –> neutrally charged particles –> able to move more freely in mucous; mucopenetration increases.

Question 15

What are ideal properties for systemic drugs delivered through nasal mucosa?

Answer 15

Molecular weight –> <500Da
Moecular shape –> globular
pKa –> non-ionised at nasal pH 5.5-6.3, 8.3 in rhinitis
logP –> <5
Solubility –> in suspension, should rapidly dissolve in mucous

Question 16

What are common nasal formulations?

Answer 16

Liquids, sometimes semi-solids, rarely powders

Sprays optimal –> can reach deeper into nose but can only administer non-viscous solutions

Drops convenient but no dose precision

Question 17

Nasal formulation excipients to adjust

Answer 17

Osmolarity –> hyperosmotic irritant to mucosa
Viscosity –> more viscous can retain at site of action for longer
Drug solubility –> needs to be dissolve to be absorbed. also, may not have a long time in nose to dissolve then be absorbed, so cut down one step first
Formulation pH –> as close to nasal pH to be non-irritating

Question 18

How do nasal formulations reach the brain?

Answer 18

Olfactory bulb –> goes to CSF & brain

Trigeminal nerve –> goes to brain

Question 19

Common formulations for laryngeal/pharyngeal administration?

Answer 19

Gargles

Throat sprays

Lozenges

Gums

–> hard to get prolonged effect due to constant swallowing

Question 20

Dental drug delivery

Answer 20

Toothpaste

• Fluoride
• Abrasives –> remove plaque off teeth
• Flavours
• Humectants –> retain moisture in formulation
• Detergents –> foaming when brushing teeth, easier for fluoride to reach more places

Mouthwash

Question 21

Gingival depots

Answer 21

Placed between tooth and gum

Slow release of doxycycline over 21 days

Question 22

Dental sponges

Answer 22

Geletamp

• Sponge inserted into tooth scket after extraction
• Porous structure that absorbs blood –> promote thrombocyte aggregation, stabilise coagulum
• Prevents infections entering site
• Resorbed in 4 weeks

Question 23

Oromucosal drug delivery

Answer 23

Good wetting & mucoadhesion –> lots of movement in mouth

Question 24

Systemic drug delivery through mouth

Answer 24

Sublingual eg. GTN

Buccal eg. prochlorperazine

–> fast absorption due to thin membrane, short distance to bloodstream

Question 25

What are SIX advantages of oromucosal systemic delivery?

Answer 25

Easy to administer
Avoid first-pass metabolism
Avoid gastric environment
Little dose variation
Rapid onset of action (sublingual)
Sustained delivery possible (buccal)

Question 26

What are FIVE disadvantages of oromucosal systemic delivery?

Answer 26

Small surface area limits drug dose
Bitter/nauseating drugs not tolerated since so close to tongue
Drug needs to be stable at salivary pH
Dissolution of drug in saliva can result in swallowing –> this becomes oral administration
Only absorbed by passive diffusion (small, unionised, lipophilic)