Ocular Drug Delivery

Question 1

What are the barriers to topical ocular drug delivery?

Answer 1

Poor permeability of the cornea
Tear reflex
Nasolacrimal drainage
Blinking
Non-corneal absorption

Question 2

Describe the cornea as a barrier

Answer 2

The corneal epithelium is a hydrophobic tissue and contributes 90 % of the barrier to hydrophilic drugs and 10 % to hydrophobic drugs;

Question 3

Describe the stroma as a barrier

Answer 3

The stroma is hydrophilic tissue (70-80 % is water; 20-25 % is collagen, proteins and mucopolysaccharides). It is the main barrier to extremely hydrophobic drugs

Question 4

What parts of the eye are involved in non-corneal absorption? What molecules pass through this route?

Answer 4

Penetration across conjunctiva and underlying sclera into vitreous humour;
This route is important for hydrophilic drugs and large molecules such as insulin

Question 5

What approaches can be taken to optimise topical ocular drug delivery?

Answer 5

1. proper placement of eye drops
2. Reducing the instilled volume of an eye drop
3. Formulation approaches

Question 6

Describe the proper placement of eye drops

Answer 6

A drop is placed in the inferior cul-de-sac by gently pulling the lower lid away from the globe and creating a pouch to receive the Drop. After gently lifting the lid to touch the globe, a small amount of liquid is entrapped in the inferior conjunctival sac, where it may be retained up to twice as long as when it is simply dropped over the superior sclera.

Question 7

Whats the typical volume delivered by commercial eye droppers compared to optimal?

Answer 7

commercial eyedroppers are in the range of 35-56 micro L

Optimal volume for instilled eye-drops is 8-15 micro L

Question 8

Describe how latanoprost is a prodrug

Answer 8

inactive until it is hydrolysed by esterases in the cornea

Question 9

what formulation approaches can be taken to to improve precorneal retention?

Answer 9

Viscous systems (polyvinyl alcohol, hydroxyethylcellulose)
Mucoadhesives (Carbopols or Carbomers)
Phase transition systems (in situ gelling systems)
- changes in pH (cellulose acetate phtalate and Carbomer solutions will form gel when in contact with the tear fluid pH 7.4);
- changes in temperature (Pluronics

Question 10

Give an example of an in situ gelling product

Answer 10

Fucithalmic® viscous eye drops

Question 11

What are soft contact lenses usually made out of?

Answer 11

hydrogels or silicone-based elastomers

Question 12

What are the problems with medicated contact lenses?

Answer 12

Burst release profiles

Poor loading capacity for many drugs

Question 13

What were the approaches to improve the performance of medicated contact lenses?

Answer 13

1. Multilayered lenses
   zero order release kinetics
   therapeutically relevant concentrations for 1 month
2. Drug-loaded nanoparticles within the lenses
   PHEMA hydrogel lenses
   Lidocaine entrapped in organocilica nanocapsules

Question 14

Describe an ocular insert e.g. Ocusert and how it works?

Answer 14

Ocusert (Alza Corporation, USA) is an insoluble ophthalmic insert classified in the group of diffusional systems.
It consists of a central reservoir of drug (e.g. pilocarpine) enclosed between two semi-permeable membranes which allow the drug to diffuse from the reservoir at a precisely determined rate for a period of 7 days;

Question 15

Despite the potential for prolonged release for several days, what is the max duration it is recommended to wear an ocular insert?

Answer 15

12 hours

Question 16

What is Mydriasert?

Answer 16

It is an opthalmic insert containing 0.28mg of tropicamide and 5.4mg of phenylephrine hydrochloride

Question 17

What is intraviteral injections?

Answer 17

Direct intravitreal injection of drugs into the vitreous cavity is employed to achieve higher drug concentrations in the vitreous and the retina

Question 18

What are the disadvantages with using intraviteral injections?

Answer 18

Therapy requires repeated injections to maintain drug concentrations at effective levels

= Patient discomfort
complications such as vitreous hemorrhage, infection, and lens or retina injury

Question 19

What is OZURDEX?

Answer 19

OZURDEX® is a sustained-release, biodegradable implant containing the corticosteroid dexamethasone;

One implant contains 700 mcg
of dexamethasone;

The implant is approximately 0.46 mm
in diameter and 6 mm in length

Question 20

What is OZURDEX indicated for?

Answer 20

treatment of adult patients with visual impairment due to diabetic macular oedema inflammation of the posterior segment of the eye presenting as non-infectious uveitis

Question 21

What is Iontophoresis?

Answer 21

It is a non-invasive technique in which a small electric current is applied to enhance ionised drug penetration into tissue.

Question 22

How does Iontophoresis work?

Answer 22

The drug is applied with an electrode carrying the same charge as the drug, and the ground electrode, which is of the opposite charge, is placed elsewhere on the body to complete the circuit. The drug serves as a conductor of the current through the tissue