Taylor Opthalmic

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What are examples of anterior eye diseases

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1

What are examples of anterior eye diseases

Dry eye, blepharitis, conjunctivitis, keratitis, glaucome

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2

Drug delivery for anterior eye diseases

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

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3

Drug clearance / elimination in the anterior eye

Nasoclarimal drainage

Blinkin

Tear duct

conjunctival vasculature

Protein binding

Metabolism & efflux pumps

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4

Examples of posterior eye diseases

•Diabetic retinopathy

•Macular degeneration

•Retinitis pigementosa

•Uveitis

•Endophthalmitis

•Proliferative vitreoretinpathy

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5

Drug delivery for posterior eye diseases

Intravitreal injections

Surgical implants

Gene/stem cell therapy

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6

Drug delivery for posterior eye diseases must by pass which barrier

Blood-retinal barriers

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7

Drug clearnace/elimination in the posterior eye

Choroidal vasculature (size and charge dependent)

Aqueous humor or uveoscleral outflow

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8

Obstacles/ problems to treating posterior eye diseases

Blood-retinal barriers

risk of retinal detachment, glaucoma, cataract, infection

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9

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

Hydrophillic drugs because of tight junctions and efflux pumps

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10

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

The conjunctiva

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11

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

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12

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

Mealnin (not fully understood)

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13

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

Reflex tears
Reflex blinking

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14

How does administration of an acidic drug affect the eye?

Causes protein aggregation and irritation

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15

What is the optimal particle size for opthalmic suspensions?

10 microns

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16

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

Apply pressure to the inner canthis

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17

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

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18

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

1-10%

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19

Pros of topical drug delivery

Easy access & localized effect

Avoid frist pass metabolism and systemic side effects

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20

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 

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21

The layers of the cornea

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

<p>Drug needs to be hydrophobic to get through epithelium but bowmans is hydrophilic so often use pro drugs </p>
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22

Layers of the tear film

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23

Nasolacrimal drainage

Tear fluid spread over surface of eye during blinking

Goes to your nasal cavity

Problem: replaced with every blink

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24

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

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25

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

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26

Drug + protein =

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

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27

Amino acid and organic anion transporters may _____

increase drug tansport into the eye

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28

Pgp

pump drugs out of eye

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29

Ideal formulation of eye drug (concen/volume)

high concentration of drug in small volume

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30

Drug uptake and biolavailability; formulation factors

1) instilled volume

2) drugs and adjuvants

3)surface tension

4)osmolality

5)pH

6)Viscosity

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31

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

True

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32

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

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33

Hypotonic:

Cells swell→ water efflux from eye surface into cornea

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34

Hypertonic:

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

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35

pH should be

neutral, acidic in contact lens wearers

pH of tears = pH of drugs bc weak buffering 

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36

How does viscosity effect retention time

High viscosity prolongs retention time

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37

Semi solid topical drug delivery systems

Ointments, Gels, In stu forming gels, liposomes

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38

Solid topical drug delivery systems

Micro/nanoparticles

Inserts (punctal pugs)

Contact lenses

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39

Advantages of solutions

Easy to prep

Inexpensive

Easy to use

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40

Disadvantages of solutions

Cannot sustain high drug concentrations

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41

Polyvinylalcohol and methyllcellulose

increase viscosity and residence time

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42

Simple eyelid closure

decreases systemic drug exposure

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43

Suspensions

For poorly water soluble drugs

Depot effect, particles stick on conjunctiva

Longer residence time on cornea

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44

Ointment advantages

Increased viscosity—> increased contact time

Lipid soluble drug in lipophiliv base

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45

Ointment disadvantages

Partition from ointment to tears—> limited absorption

Limited patient compliance

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46

Emulsion eye drops

1) Electrolytres in tears dissolve polymer matrix

2)Emulsion components are released

3)Oil enhances lipid layer

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47

limitations to topical drug delivery

•Tear turnover

•Drainage

•Metabolism

•Protein binding

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48

Strategies to increase tear film contact time

Mucoadhesive polymers

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49

Strategies to increase corneal permeability

Prodrugs

Penetration enhacers

Drug-cyclodextrin complexes

Lipid based carriers

Iontophoresis

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50

Iontophoresis pros

Increase permability

Wide variety of drugs

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51

Iontophoresis cons

Cannot sustain drug concentrations

Mild pain & burns

Questionabke efficacy for chronic diseases like galucoma, macular degen

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52

Ocular drug delivery methods

Topical

Intravitreal injections

Intraocular implants

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53

Intravitreal injection pros

Bypass the blood retinal barriers

achieve high drug levels in retina

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54

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

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55

Punctal plugs pros

decreased dose, increased efficacy, sustained delovery

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56

Barriers for Ocular Delivery to posterior eye

→ Corneal barrier

→ Conjunctiva/choroid barrier

→Blood retinal barriers

•Inner retinal vasculature

•REntinal pigment epithelium

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57

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)

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58

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)

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59

Micro and nanoparticles pros cons

Pros: May increase half-life of drug

Cons: Requires injection; may cause vitreous clouding

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60

Liposomes pros cons

Pros: Increase half-life and limit toxicity

Cons: Requires injection; vitreous clouding

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61

Trans-scleral iontophoresis pros & cons

Pros: Non-invasive technique

Cons: Does not increase drug half-life

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