Taylor Opthalmic

What are examples of anterior eye diseases

Dry eye, blepharitis, conjunctivitis, keratitis, glaucome

Drug delivery for anterior eye diseases

Solutions, ointments, emulsions, ocualr inserts, punctal plugs, Iontophoresis

Drug clearance / elimination in the anterior eye

Nasoclarimal drainage

Blinkin

Tear duct

conjunctival vasculature

Protein binding

Metabolism & efflux pumps

Examples of posterior eye diseases

•Diabetic retinopathy

•Macular degeneration

•Retinitis pigementosa

•Uveitis

•Endophthalmitis

•Proliferative vitreoretinpathy

Drug delivery for posterior eye diseases

Intravitreal injections

Surgical implants

Gene/stem cell therapy

Drug delivery for posterior eye diseases must by pass which barrier

Blood-retinal barriers

Drug clearnace/elimination in the posterior eye

Choroidal vasculature (size and charge dependent)

Aqueous humor or uveoscleral outflow

Obstacles/ problems to treating posterior eye diseases

Blood-retinal barriers

risk of retinal detachment, glaucoma, cataract, infection

The corneal epithelium is the main barrier to which type of drugs and why?

Hydrophillic drugs because of tight junctions and efflux pumps

Which has a larger surface area, the conjunctiva or the cornea?

The conjunctiva

Which is a better route for drug entry, the conjunctiva or the cornea?

The cornea, bc the conjunctiva has a large blood supply that goes into systemic circulation

Drugs binding to ____ in the iris can have a depot effect, why?

Mealnin (not fully understood)

What are the two responses that increase clearance of drugs that irritate the eye?

Reflex tears
Reflex blinking

How does administration of an acidic drug affect the eye?

Causes protein aggregation and irritation

What is the optimal particle size for opthalmic suspensions?

10 microns

How can one minimize nasolacrimal drainage when administering a drug topically to the eye?

Apply pressure to the inner canthis

How do preservatives like benzalkonium chloride affect the eye?

Can remain in the eye for a long time

Can increase intraocular pressure when used for a long time

What percentage of administered dose is actually absorbed into the eye?

1-10%

Pros of topical drug delivery

Easy access & localized effect

Avoid frist pass metabolism and systemic side effects

Barriers to topical drug delivery

1. Cornea; major barrier 

2. Iris: melanin binds drugs

3. Tear duct: nasolactrimal clearance

4. Conjunctiva: vascular, increased clearance

5. Ciliary body: produces aqueous humor 

The layers of the cornea

Drug needs to be hydrophobic to get through epithelium but bowmans is hydrophilic so often use pro drugs

Layers of the tear film

Nasolacrimal drainage

Tear fluid spread over surface of eye during blinking

Goes to your nasal cavity

Problem: replaced with every blink

Conjunctiva

White of the eye

Mucin is produced

Larger surface area and more permeable to drug that cornea

Major route for systemic circulation

→Major factor in drug loss

Physiological factors affecting drug uptake & bioavailability

1)Tear film and nasolacrimal drainage

2)Eyelid movements, blinking

3)Protein binding

4)Metabolism & efflux

5)Conjunctival loss

Drug + protein =

Drug-protein complex which is an inactive form of the drug

Amino acid and organic anion transporters may _____

increase drug tansport into the eye

Pgp

pump drugs out of eye

Ideal formulation of eye drug (concen/volume)

high concentration of drug in small volume

Drug uptake and biolavailability; formulation factors

1) instilled volume

2) drugs and adjuvants

3)surface tension

4)osmolality

5)pH

6)Viscosity

T/F Smaller volume → slower drainage→ increased residence time

True

What happens if a drug lowers surface tension?

Lipid layer becomes disrupted leading to the tear film evaporating, this leads to dry spots that are painful and the drug is removed by blinking

Hypotonic:

Cells swell→ water efflux from eye surface into cornea

Hypertonic:

water flows from aqueous layer through cornea to surface → loss of drug and loss of surface cells

pH should be

neutral, acidic in contact lens wearers

pH of tears = pH of drugs bc weak buffering 

How does viscosity effect retention time

High viscosity prolongs retention time

Semi solid topical drug delivery systems

Ointments, Gels, In stu forming gels, liposomes

Solid topical drug delivery systems

Micro/nanoparticles

Inserts (punctal pugs)

Contact lenses

Advantages of solutions

Easy to prep

Inexpensive

Easy to use

Disadvantages of solutions

Cannot sustain high drug concentrations

Polyvinylalcohol and methyllcellulose

increase viscosity and residence time

Simple eyelid closure

decreases systemic drug exposure

Suspensions

For poorly water soluble drugs

Depot effect, particles stick on conjunctiva

Longer residence time on cornea

Ointment advantages

Increased viscosity—> increased contact time

Lipid soluble drug in lipophiliv base

Ointment disadvantages

Partition from ointment to tears—> limited absorption

Limited patient compliance

Emulsion eye drops

1) Electrolytres in tears dissolve polymer matrix

2)Emulsion components are released

3)Oil enhances lipid layer

limitations to topical drug delivery

•Tear turnover

•Drainage

•Metabolism

•Protein binding

Strategies to increase tear film contact time

Mucoadhesive polymers

Strategies to increase corneal permeability

Prodrugs

Penetration enhacers

Drug-cyclodextrin complexes

Lipid based carriers

Iontophoresis

Iontophoresis pros

Increase permability

Wide variety of drugs

Iontophoresis cons

Cannot sustain drug concentrations

Mild pain & burns

Questionabke efficacy for chronic diseases like galucoma, macular degen

Ocular drug delivery methods

Topical

Intravitreal injections

Intraocular implants

Intravitreal injection pros

Bypass the blood retinal barriers

achieve high drug levels in retina

Intravitreal injection cons

Retinal detachment

Endophthalmitis

Risk of glaucoma and cataract

Drug cleared by passive diffusion or active secretion into system circulation

Poor patient compliance

Punctal plugs pros

decreased dose, increased efficacy, sustained delovery

Barriers for Ocular Delivery to posterior eye

→ Corneal barrier

→ Conjunctiva/choroid barrier

→Blood retinal barriers

•Inner retinal vasculature

•REntinal pigment epithelium

Non-biodegradable implants Pros, cons & examples

Pros: Steady, controlled release of drug over long periods

Cons: Surgical insertion, replacement and removal

Examples: Vitraset (Ganciclovir), Retisert (fluocinolone)

Biodegradable implants pros cons & examples

Pros: Made into various shapes, injected in office procedure; no removal required

Cons: Surgical implantation or removal

Examples: Posurdex (Dexamethasone)

Micro and nanoparticles pros cons

Pros: May increase half-life of drug

Cons: Requires injection; may cause vitreous clouding

Liposomes pros cons

Pros: Increase half-life and limit toxicity

Cons: Requires injection; vitreous clouding

Trans-scleral iontophoresis pros & cons

Pros: Non-invasive technique

Cons: Does not increase drug half-life