Ocular Drug Delivery

Question 1

What are the Ocular barriers in drug delivery

Answer 1

Poor permeability in the cornea

Nasolacrimal drainage

Tear reflex

Blinking

Non-corneal absorption

Question 2

What is the corneal barrier and how does it have this barrier, give an example

Answer 2

Corneal is relatively impermeable compared to other tissues

Hydrophobic tissue: 90% barrier to hydrophilic drugs and 10% hydrophobic drugs

Stroma: hydrophilic tissue, barrier to hydrophobic drug

Enzymes: esterases, petidases, proteases include cornea

Question 3

If the pH is lower than 4 or higher than 10 in the eye, what can that lead to ?

Answer 3

Copious lacrimation and damage

Question 4

What is non corneal absorption and where is this route important in

Answer 4

1. The penetration of conjunctiva and underlaying sclera into the vitreous humour
2. Route important for:
   Hydrophilic molecules and large molecules- due to cornea being relatively impermeable to hydrophilic drugs

Question 5

Describe the approach to optimise topical ocular delivery through proper placement of eye drops

Answer 5

1. Drop placed in inferior cul-de-sac through gently pulling lower eye lid- create pouch
2. Small amount of liquid is then entrapped into inferior conjunctival sac- where retained twice as long
3. This is compared to superior sclera

Question 6

Describe the approach to optimise topical ocular delivery through reducing instilled eye drop dose

Answer 6

Optimal value: 8-15 micro litres

Typical amount per eye drop: 35 to 56 micro litres: value is too high as eyes can only retain certain amount

Question 7

Describe the approach to optimise topical ocular delivery through formulation approaches

Answer 7

1. Modify integrity of corneal epithelium through chelating agent and surfactant use
2. Modify chemical structure using pro-drug approach- drug becomes hydrophobic due to enzymes in eye

Question 8

Give an example of adrenaline as a pro drug

Answer 8

Dipivoyl epinephrine converted to epinephrine

Question 9

Give an example of a prodrug used in the eye and its role

Answer 9

1. Latanoprost: used to control intraocular pressure which can control progression of glaucoma and ocular hypertension
2. Inactive: until hydrolysed by esterase in the cornea

Question 10

What are the formulation approaches to improve pre-corneal retention

Answer 10

1. Viscous systems: poly vinyl alcohol, hydroxyethyl cellulose
2. Muco-adhesives: carbopols, carbomers
3. Phase transition systems: insitu gelling systems
4. Changes in pH (cellulose acetate phthalate and carbomer solutions will make gel when in contact with tear fluid pH = 7.4
5. Changes in temperature

Question 11

Give an example of a commercial in situ gelling product

Answer 11

Fucithalmic viscous eye drops:
Fusidic acid 1% w/w
Benzalkonium chloride
Disodium edetate

Question 12

Give examples of the materials that make up contact lenses

Answer 12

1. Polymethylmetacrylate (PMMA): provides opportunity to use other materials
2. Contact lenses: Hard or soft lenses according to modulators of elasticity
3. Examples: Hydrogels or silicone based elastomers

Question 13

How do you improve the performance of medicated contact lenses

Answer 13

PHEMA: hydrogel coating

PLGA: poly lactic acid coglycolic acid film

Zero order kinetics

Therapeutically relevant connotations of up to 1 month

Question 14

What are ocular inserts and give an example of a drug used in this way

Answer 14

1. An insoluble device that is formed of two semi permeable membranes that contains a drug Example: pilocarpine
2. Drug diffuses over period of 7 days
3. Results: Decreased intraocular pressure that is achieved in patients with hypertensive open angled glaucoma

Question 15

How are Mydriasert containing 0.28mg Tropicamide and 5.4mg of phenylephrine hydrochloride used

Answer 15

Ophthalmic insert

Question 16

What other intraocular drug delivery methods are there

Answer 16

Intravitreal injections

Liposomes

Micro-particulates and nano-particulates

Intraocular devices (implants)

Iontophoresis

Question 17

Describe intravitreal injections use and the problems that may occur from this

Answer 17

1. Direct injection of drug into the vitreous cavity to achieve higher drug concentrations
2. Half life of drugs: shorter
3. Repeated injections: necessary to maintain drug at effective therapeutic level over time
4. Problems: repeat injections lead to vitreous haemorrhage, infections, lens or retinal injury

Question 18

What is Ozurdex and its use

Answer 18

1. Sustained release biodegradable implant: contains steroid dexamethasone
2. Indication: macular oedema inflammation of the posterior segment of the eye presenting as non infectious uveitis

Question 19

What is iontophoresis

Answer 19

Non invasive technique used to allow drugs to diffuse through the impermeable cornea

Drug is carried via positive electrode which carries positive drug into the tissue and ground electrode