OCULAR DRUG DELIVERY

Question 1

What types of ocular barriers are there in topical drug delivery?

Answer 1

1. Poor permeability of the cornea
2. tear reflex
3. nasolacrimal drainage
4. blinking
5. non-corneal absorption

Question 2

Describe the corneal epithelium in terms of permeability?

Answer 2

Corneal epithelium is relatively impermeable, a hydrophobic tissue, contributes to 90% of the barrier to hydrophilic drugs, 10% to hydrophobic drugs

Question 3

Describe the stroma in terms of permeability?

Answer 3

Hydrophilic tissue, made up of 70-80% water and 20-25% collagen, proteins,
MAIN barrier to hydrophobic drugs

Question 4

How can non-corneal absorption contribute to ocular bioavailability?

Answer 4

penetration across conjunctiva & underlying sclera into vitreous humour; route is important for hydrophilic drugs and large molecules such as insulin.
conjunctival permeability of hydrophobic drugs typically one order of magnitude greater than corneal permeability
sclera is also more permeable than cornea.

Question 5

What is the proper placement of eyedrops?

Answer 5

not directly onto cornea, onto conjunctiva area, gently pull out lower eyelid and place drop. then blink

Question 6

How can reducing the instilled volume of an eyedrop optimise drug delivery?

Answer 6

optimal vol for instilled eye drops is 8-15Ul, typically volumes in commercial eye drops 35-56Ul.
only small proportio. of the eyedrop can be retained by the eye.

Question 7

How can modifying integrity of corneal epithelium optimise drug delivery?

Answer 7

exposing the eye to compounds such as chelating agents and surfactants. however rarely explored as eye is sensitive organ

Question 8

How can modifying the chemical structure of the drug optimise drug delivery?

Answer 8

pro-drug approach. molecule consists of API, but if API is less efficient at permeation through biological barriers (too hydrophilic/too charged) THEN it is converted into prodrug, chemically linked with a molecule that will modify properties of API.
linkage is biodegradable

Question 9

How does the prodrug dipivefrin hydrolyse to form adrenaline?

Answer 9

Dip - more hydrophobic molecules which give better absorption.

adrenaline - hydrophilic groups substitutes with the hydrophobic groups to form esters.

When dip moves through cornea, ester bonds are cleaved releasing adrenaline, providing a more efficient pharmacological effect.

Question 10

Latanoprost as a prodrug?

Answer 10

isopropyl group linked by ester group to the main molecule - inactive until it is hydrolysed by esterases in the cornea

Question 11

what different formulation approaches are there to improve precorneal retention?

Answer 11

viscous systems
mucoadhesives
phase transition systems
changes in pH. changes in temperature. changes in ion compositions

Question 12

Name the API and excipients in timoptol gel-forming eye drops

Answer 12

0.25% or 0.5% timolol maleate API
Gellan gum - gelling agent
trometamol - pH adjustment
Mannitol - to reduce ocular irritation caused by the preservative
Benzododecinium bromide - preservative
Water for injections - solvent

Question 13

how does timoptol exert the gelling effect?

Answer 13

gelling agent (gellan gum) goes through the process of gelation

Question 14

Name the API and excipients in Fucithalmic viscous eye drops?

Answer 14

Fusidic acid 1%
disodium edetate
sodium hydroxide - pH adjustment
Mannitol - to reduce ocular irritation caused by the preservative
Benzalkonium chloride - preservative
Water for injections - solvent

Question 15

How do Medicated contact lenses work

Answer 15

Hydrogel lenses soaked in drug solution, placed onto eye and ensure delivery of drug into eye, as can sit on eye for long time

Question 16

what are some problems with medicated contact lenses

Answer 16

burst release profiles, bc drug molecules release from the lens very quickly
poor loading capacity, more drugs are hydrophobic

Question 17

How does the approach of multilayered lenses improve performance of medicated contact lenses?

Answer 17

hybrid lenses
PHEMA, hydrogel coating
PLGA poly(lactic acid co glycolic acid film) which is hydrophobic and can load onto hydrophobic space
slowest release from lens, so could lead to 0 order release kinetics and therapeutically relevant conc for long period of time

Question 18

How does the approach of drug-loaded nanoparticles improve performance of medicated contact lenses?

Answer 18

PHEMA hydrogel lenses
lidocaine entrapped in organosilica nanocapsules
nanoparticles impregnated into a hydrophilic contact lens material/ nanoparticles small so will not inhibit light transmission through lens, nanoparticles won’t be released from lens
release of drug molecules delayed

Question 19

what are ocular inserts

Answer 19

insoluble opthalmic insert
delivers drug for longer period of time (7days)

Question 20

What is a disadvantage of the insolubility of the ocusert device? (DISCONTINUED)

Answer 20

insoluble, stays on surface on eye for long time, tend to swell and partially fragment after long time, recommended they not be worn for more than 12 hours, then discontinued

Question 21

what is Mydriasert?

Answer 21

insert containing 0.28mg of tropicamide and 5.4mg of phenylephrine hydrochloride
administered it causes pupil dilation, needed sometimes for surgery and diagnostic purposes

Question 22

Intraocular drug delivery

Answer 22

intravitreal injections
liposomes - not commercialised
microparticulates and nanoparticles
implants
iontophoresis

Question 23

describe intravitreal injections

Answer 23

intravitreal injections into vitreous cavity to achieve high drug concentrations in the vitreous and the retina

Question 24

name the complications of intravitreal injections

Answer 24

half life relatively short
repeated injections required to maintain conc at an effective therapeutic effect
this results in patient discomfort
may lead to complications such as vitreous hemorrhage, infection, lens/retinal injury

Question 25

describe what OZURDEX is indicated for

Answer 25

sustained release biodegradable implant containing corticosteroid dexamethasone,
treatment of adults with visual impairment due to diabetic macular oedema, inflamm of the posterior segment of the eye presenting as non-infectious uveitis