Ocular Drug Delivery

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

Relatively impermeable hydrophobic tissue that contributes 90 % of the barrier to hydrophilic drugs and 10 % to hydrophobic drugs.

Hydrophilic tissue (70-80 % is water; 20-25 % is collagen, proteins and mucopolysaccharides).
Main barrier to extremely hydrophobic drugs;
Significant levels of various enzymes (esterases, peptidases, proteases) in ocular tissues including cornea.
Many ocularly applied drugs metabolised during or after absorption.

Penetration across conjunctiva + underlying sclera into vitreous humour;
Route for hydrophilic drugs + large molecules; insulin;
Conjuctival permeability of hydrophilic drugs typically 1 order of magnitude greater than corneal permeability;
Sclera more permeable than cornea.

Proper placement of the eyedrops
Drop placed in inferior cul-de-sac by gently pulling lower lid away from globe + creating pouch to receive drop.
After gently lifting lid to touch globe, small amount of liquid entrapped in inferior conjunctival sac, where its retained up to 2x as long as when simply dropped over superior sclera.
Reducing the instilled volume of an eyedrop
Optimal volume for instilled eye-drops is 8-15 mL;
Typical volumes delivered by eyedroppers between 35-56 mL;
Only small proportion of eye-drop retained by eye.

Modify integrity of the corneal epithelium transiently - (exposing eye to compounds such as chelating agents and surfactants.
Hardly explored; sensitivity of the particular tissue.
Modify chemical structure of drug (pro-drug approach)

Dipivoyl epinephrine (dipivefrine) -> Epinephrine (adrenaline)
More hydrophobic, better absorption

Medication administered into eyes to control glaucoma progression of or ocular hypertension by reducing intraocular pressure.
Inactive until it is hydrolysed by esterases in the cornea.

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 tear fluid pH 7.4);
Temp Changes (Pluronics)
Changes in ions composition (gellan gum, sodium alginate)

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.

· Fusidic acid 1% w/w;
· disodium edetate;
· Mannitol;
· Carbomer;
· sodium hydroxide;
· Benzalkonium chloride;
· Water for injections

Contact lenses classified as either hard or soft contact lenses according to their modulus of elasticity.
Soft contact lens is either hydrogels or silicone-based elastomers.
Hard lenses generally have a smaller diameter.

· Burst release profiles
· Poor loading capacity for many drugs

Multilayer lenses
· PHEMA - hydrogel coating
· PLGA - poly(lactic acid-co-glycolic acid film)
· Zero-order release kinetics;
· Therapeutically relevant concentrations for 1 month
Drug-loaded nanoparticles within the lenses
· PHEMA hydrogel lenses
· Lidocaine entrapped in organosilica nanocapsules

Ocusert is an insoluble ophthalmic insert classified in the group of diffusional systems.
Consists of a central reservoir of drug; pilocarpine enclosed between 2 semi-permeable membranes, allows drug to diffuse from the reservoir at a precisely determined rate for 7 days;
Prolonged reduction in intraocular pressure achieved with a single Ocusert in patients with hypertensive open-angle glaucoma.
Due to insolubility of the Ocusert device - must be removed after use. Inserts well tolerated, but after prolonged wear tends to swell and partially fragment.
Recommended to not wear for more than 12 h, despite the potential for prolonged release of several days.

Each ophthalmic insert contains 0.28 mg of tropicamide and 5.4 mg of phenylephrine hydrochloride
Excipients: ammonio-methacrylate copolymer (Type A), polyacrylate dispersion, glycerol dibehenate and ethylcellulose

Intravitreal injections
Liposomes -
- Has potential to increase activity and prolong residence of drug in eye. Liposomes also reduce intraocular toxicity of certain potent drugs.
· Microparticulates and nanoparticles
· Intraocular devices (implants)
· Iontophoresis

Direct intravitreal injection of drugs into vitreous cavity is employed to achieve higher drug concentrations in the vitreous and the retina;
Half-life of drugs in the vitreous is relatively short;
Repeated injections needed to maintain drug concs at effective therapeutic level over a certain period of time
Repeated intravitreal injections results in patient discomfort, may lead to complications; vitreous hemorrhage, infection, and lens or retinal injury

A sustained-release, biodegradable implant containing the corticosteroid dexamethasone;
1 implant contains 700 mcg of dexamethasone;
~ 0.46 mm in diameter and 6 mm in length;
Indicated for treatment of adults with visual impairment due to diabetic macular oedema inflammation of the posterior segment of the eye presenting as non-infectious uveitis;
Excipients: 50:50 poly(D,L-lactide-co-glycolide)