Topic 2J Ophthalmic Drug Delivery

Question 0

Physiological factors affecting topical ocular drug delivery (7)

Answer 0

1. Nasolacrimal drainage
2. pH
3. Surface tension
4. Osmolality
5. Hydrophilic and lipophilic barriers
6. Protein binding
7. Drug metabolism

Question 1

How does the cornea provide an effective barrier to ocular drug delivery (7)

Answer 1

The cornea is a 5 layered structure.
The combination of all theses layers increases the path length

The endothelium has the NA+/K+ATPase pump which controls the passive movement of water into the stoma and out. It is responsible for maintaining corneal transparency and constant corneal thickness. It the pump breaks down the stoma will absorb water, swell and become opaque. This thickening and clouding of the cornea affects the absorption of a drug by increase in path length.

Question 2

Describe the use of bioadhesives in optimising ocular drug delivery with specific reference to mucoadhesion (6)

Answer 2

1. Employes a mucous covered membrane (mucoadhesion) which:
2. • localises a dosage form within a region increasing drug
     bioavailability
3. • permits modification of tissue permeability in a restricted region
4. • reduces dosing frequency
5. The presence of mucin allows bioadhesive polymers to thicken the tear film.
6. 2 possible adhesion mechanisms
   - hydrogen bonding
   - interpenetration

Question 3

Explain the mechanisms sodium hyaluronate is effective in optimising ocular drug delivery (5)

Answer 3

Sodium hyaluronate is a high MW polymer. Used as a substitute for vitreous humour and helps to promote tissue repair. It has a protective effect by providing a stabilised hydrogel. It’s unusual rheological quality produces a rapid transformation from liquid to a solid with increasing stress. This thickens the tear film causing slow drainage and improved distribution on the cornea when blinking.
The carboxyl groups of hyaluronate form H bonds with sugar OH groups of mucin causing intimate contact with the cornea.
These properties give hyaluronates great potential in ocular delivery.

Question 4

Describe the use of phase transition systems in optimising ocular drug delivery (6)

Answer 4

Phase transition on the eye surface: Sol phase. Gel phase
1. Change in pH
Eg: cellulose acetate phlalate pH 5. pH 7.4

2. Change in temperature
   Eg: poloxamer F127. Room temp 34*C
3. Activation by ions
   Eg: gellan gum. No tears. Na+ tears

Question 5

Explain the use of nano and micro particulates as an approach to enhancing topical ocular drug delivery (5)

Answer 5

**Nano particles are colloidal particles ranging from 10-1000nm in which a drug may be entrapped, encapsulated or absorbed.

Micro particles are drug containing polymeric particles within the size of 1-10um which are suspended in a liquid carrier medium.
Particles reside at the delivery site and drug is released through diffusion.

Question 6

Deficiencies in current intraocular therapy with specific reference to implants (5)

Answer 6

1. risk of endophthalmitis
2. risk of retinal detachment
3. surgical removal
4. Short or variable duration of therapy
5. Tissue toxicity and safety