RESP - D. DRUG DELIVERY TO THE EYE-COVERED

Question 1

what are the 2 segments of the eye

Answer 1

anterior = in front of lens
posterior = behind lens

• no connection between 2 segments
• connection between anterior and nasal cavity through nasal lacrimal duct

Question 2

protective mechanisms to protect cornea which can’t repair itself if damaged

Answer 2

• eyelids: windscreen wipers
• reflex binding: anything that touches cornea - rapid closing of eyelid
• tear film: continuously produced by lacrimal gland

Question 3

what are the 3 layers of a tear film

Answer 3

1. upper is lipidic (prevents evaporation)
2. intermediate is aqueous (pH 7.4 with low buffering capacity, salts, proteins, glucose)
3. lower is mucous (prevents cornea drying) - in contact with cornea and sticks tear film at surface of cornea

drained into nasal cavity through nasolacrimal duct as volume of tears needs to remain constant at all times

Question 4

ophthalmic delivery

Answer 4

anterior segment:
- accessible through cornea
- topical delivery: eyedrops
- 90% dose wasted
- 1-5% absorbed across cornea into anterior chamber

posterior segment:
- systemic delivery of very high doses so side effects
(antibiotic by oral route)
- intraocular (through cornea) injections are very invasive and risky
- polymeric implants (in vitreous body) for sustained release over months to avoid repeated injections (need surgery for this)

Question 5

why is there low absorption into anterior segment - tear drainage

Answer 5

• eye drops 30-70microlitres but tear volume is 10microlitres
• eyedrops induce reflex blinking
• 20-30microlitres lost on cheeks
• excess drainage into nose
• contact time with cornea: 2-3 minutes
• drug diluted by tear film so low conc in contact with cornea

Question 6

why is there low absorption into anterior segment - absorption into systemic circulation

Answer 6

• from nasal mucosa as nasal cavity is very permeable
• from GIT after drainage to nose (nose in contact with throat)
• from conjunctiva (more drug absorbed here than cornea as larger, permeable, well vascularised)

Question 7

why is there low absorption into anterior segment - protein binding

Answer 7

• in tear film
• in cornea and aq humour

Question 8

why is there low absorption into anterior segment - corneal barrier

Answer 8

• small SA
• not very permeable: multilayered epithelium with tight junctions
• drugs must cross cell layers (lipophilic) and stroma (hydrophilic) so need correct hydrolipophilicity

Question 9

Eye drops

Answer 9

• aq formulations of drug
• solutions or suspensions
• solution must be free of particles
• particles must be <50microns in suspensions
  particles remain in corner of eye and aren’t drained into nasal cavity but dissolve slowly in tear film so increased contact b/n drug and cornea and higher bioavailability across cornea
• pH close to 7.4 - this is pH of tears (buffers used, alkali pH less irritant than acidic pH)
• isotonic (hypo better than hyper as will dry cornea as transfer of water from cornea to surface of eye)

Question 10

sterility of eyedrops

Answer 10

• preservatives: benzalkonium chloride most efficient - people allergic to this)
• single-dose containers preferred ‘minims’ - 0.3-0.5 ml so need 2-3 drops
• max volume in each container: 10ml
• max period of use: 1 month / 7 days in hospital
• max period of use of preservative-free eye-drops: 1 week / 3 days in hospital
• very short residence time of 3-6 minutes (viscosity enhancers slightly increase retention time)

Question 11

how to prolong drug retention

Answer 11

1. correct application:
   - drop inside lower lid, eye closed, nasolacrimal duct occluded by finger (press in corner of eye so liquid not drained into nasal cavity)
2. decrease drop volume to 0.01-0.02 microlitres to decrease wastage
3. inserts:
   - small collagen or polymer-based disc placed in eye corner, too big to be drained
   - slowly release drug over few hours
4. ointments or gels
   - viscous, retained in eye corner, can’t be drained
   - blinking spreads them over cornea
   - blur vision (bad)

Question 12

eye ointments

Answer 12

• drug particles (max 50microns) dispersed in a semi-solid greasy base (yellow soft paraffin, liquid paraffin, wool fat)
• packed sterile in plastic or aluminium tubes fitted with a sterile canula (max 10g) for easy application
• preservatives not required as bacterial growth unlikely due to no water
• max period of use: 1 month

Question 13

eye lotions

Answer 13

• sterile isotonic aqueous solutions used to wash eyes of irritants/pollens
• can just be a saline solution (for allergies)
• large container (max 200ml)
• supplied with plastic eye bath
• max period of use: 1 month / 7 days in hospital
• same formulation as for eyedrops
• if for first aid, no preservative included and solution must be discarded after 24 hours