540 - Drug Delivery Systems - Exam Iv - Ocular Drug Delivery

Front 1

What are the five examples of external eye diseases?

Back 1

1) Styes
2) Blepharitis
3) Conjunctivitis
4) Corneal Edema
5) Dry eye

Front 2

What is a stye and how do you treat it?

Back 2

It is a localized inflammation of sebaceous glands of the eyelid

Tx: hot compresses; antibiotics

Front 3

What is blepharitis and how do you treat it?

Back 3

It is seborrheic dernatitis caused by S. Aureus. Symptoms include burning, itching and scaly skin in eyelids

Tx: antibiotics

Front 4

What is conjunctivitis and how do you treat it?

Back 4

It is an inflammation of the outer layer of the eye caused by viral, bacterial, allergic or chlamydial contamination. Symptoms include redness, itching and discharge.

Tx: Antihistamines, topical decongestants, antibiotics

Front 5

How do you treat corneal edema?

Back 5

Hypertonic solutions, decongestants

Front 6

How do you treat dry eye?

Back 6

Artificial tears, pilocarpine

Front 7

What are examples of causes of dry eye?

Back 7

Chronic - Sjorgens Syndrome
Acute - Drug side effect

Front 8

What are the goals of ocular drug delivery?

Back 8

1) Improve targeting to site of action
2) Prolong residence time
3) Decreases frequency of administration
4) Improve patient compliance

Front 9

What are the advantages of ocular drug delivery?

Back 9

1) Easy access for localized drug delivery
2) Achieve localized effect of drug action
3) Avoid first pass metabolism & systemic side effects

Front 10

What are the disadvantages of ocular drug delivery?

Back 10

1) Efficient clearance mechanisms
2) Blood-Ocular barriers
3) Posterior eye diseases harder to treat

Front 11

What are the routes of ocular drug administration?

Back 11

1) Intraocular implants
2) Systemic administration
3) Intravitreal Injection
4) Topical Application

Front 12

What are the disadvantages of intraocular implants?

Back 12

Increased risk of retinal detachment and intravitreal hemorrhage as well as being invasive

Front 13

What are the disadvantages of intravitreal injections?

Back 13

Increased risk of retinal detachment, hemorrhage, endophthalmitis and cataracts

Front 14

What are the disadvantages of system administration?

Back 14

Limited/variable penetration with a potential for systemic toxicity

Front 15

What are the disadvantages of topical ocular drug delivery?

Back 15

1) Limited penetration
2) Rapid tear washout
3) Poor patient compliance
4) Corneal barrier to absorption
3) Clear by conjunctival blood flow and sclera

Front 16

What are the advantages to topical ocular drug delivery?

Back 16

1) Convenient and effective for anterior eye
2) Non-invasive
3) Selective targeting, rapid onset of action
4) Avoid first pass metabolism

Front 17

What are the barriers to topical ocular drug delivery?

Back 17

1) Corena (Major)
2) Iris
3) Conjunctiva
4) Blood-aq barrier

Front 18

What are facts pertaining to the cornea?

Back 18

1) Outermost part of the eye, composed of 5 layers
2) Avascaular and transparent
3) Nourished by tear fluid and aqueous humor
4) Protects eyes from germs and dust
5) Refracts light, helps focus image and filters out UV rays

Front 19

By what route to lipophilic drugs transverse the epithelium of the cornea?

Back 19

Transcelluar

Front 20

By what route to hydrophilic drugs transverse the epithelium of the cornea?

Back 20

Paracellular

Front 21

Describe the epithelium of the cornea

Back 21

1) Multilayered
2) Tight junctions (best suited for lipophilic drugs)
3) 90% barrier to hydrophilic drugs
4) 10% barrier to hydrophobic drugs

Front 22

Describe the stroma of the cornea

Back 22

1) 70-80% water (aqueous)
2) Contains glycosaminoglycans, collagen
3) Molecular radius controls diffusion
4) Main barrier to lipophilic drugs

Front 23

What part of the cornea is the main barrier for lipophilic drugs?

Back 23

The stroma

Front 24

What barrier's in the cornea are not significant for drug penetration?

Back 24

1) Bowman's Layer
2) Desecemet's membrane

Front 25

What are facts pertaining to the conjunctiva?

Back 25

1) Highly vascular, translucent
2) Covers 80% of eye surface
3) Continuous with cornea
4) Possess 6-9 irregular arranged layers
5) Possess goblet cells
6) Has epithelia microvilli
7) Drug transporters limit absorption
8) Major route for drug to enter systemic circulation

Front 26

What do goblet cells produce?

Back 26

Mucin - a major tear component

Front 27

What are the pre-corneal factors to uptake and bio-availability?

Back 27

1) Mixing
2) Tear film dilution and nasolacrimal drainage
3) ph & Osmolarity
4) Protein binding
5) Metabolism
6) Conjunctival loss

Front 28

What are the layers to the tear film?

Back 28

From top to bottom:
1) Superficial lipid layer (protectant)
2) Aqueous Layer (anti-bacterial)
3) Mucoid layer/Microvilli (Adherence)

Front 29

When does tear film turn over decrease and what does this mean to drug delivery?

Back 29

It decreases as we age, increasing residence time of the drug

Front 30

What is the pH of normal tears?

Back 30

7.4

Front 31

What is the optimal pH for ocular drug administration?

Back 31

7.0 - 7.7
If Acidic - protein aggregation
If alkaline - loss of membrane integrity

Front 32

How does osmolarity effect ocular drug administration?

Back 32

It influences the optical integrity of the cornea.

* Hypotonic -> Cells swell -> Inc. Permeability
* Hypertonic -> tearing -> loss of drug

Front 33

What happens if instil drugs lower the surface tension?

Back 33

The tear film becomes destabilized and the drug is removed by reflex blinking

Front 34

Why must one wait to apply two drugs to the same eye?

Back 34

The drugs will compete for protein binding. Applying separately prevents drug displacement and premature clearance.

Front 35

Name the components of ophthalmic formations and their role

Back 35

1) Vehicles (Inc. Viscosity = Inc Contact Time)
2) Preservatives
3) Antioxidants (Prevent product deterioration)
4) Permeability enhancers (Inc. Corneal penetration)
5) Buffers
6) Tonicity adjusters

Front 36

What are the five types of OTC ophthalmic products?

Back 36

1) Artificial Tears
2) Lubricating Ointments
3) Vasoconstrictors (decongestants)
4) Antihistamines
5) Antioxidants

Front 37

How do you increase the bioavailability of ophthalmic drugs?

Back 37

Decrease solution drainage, tear turnover and conjunctival absorption

Front 38

List the order of ophthalmic solutions in order of increasing residence time?

Back 38

1) Solution (shortest)
2) Suspension
3) Ointment (longest)

Front 39

What are facts pertaining to ophthalmic solutions?

Back 39

1) Easy to prepare
2) Inexpensive
3) Easy to use
4) BUT... cannot sustain high drug concentrations

Front 40

What are facts pertaining to ophthalmic suspensions?

Back 40

1) Used for poorly water-soluble drugs
2) Longer residence time on cornea (particles stick to conjunctiva)
3) Slow release of drug
4) Note: Large particle size increases clearance

Front 41

What are the advantages to ophthalmic ointments?

Back 41

1) Increased viscosity (inc. contract time)
2) Higher concentration gradient via oil-soluble drug in a lipophilic base
3) Useful for pediatric administration

Front 42

What are the disadvantages to ophthalmic ointments?

Back 42

1) Miscibility (difficulty partitioning from ointment to tears)
2) Limited patient compliance due to discomfort, blurred vision
3) Some are considered unsafe for interior of the eye (Lanolin, petrolatum and vegetable oil)

Front 43

What is the benefit to mucoadhesive polymers?

Back 43

The adhesive bonding to mucin increases contact time

Front 44

Where are the ocular implants Ocusert, Prosert and Lacrisert inserted?

Back 44

Into the scleral-conjunctival space

Front 45

Which ocular implant is an erodible implant?

Back 45

Lacrisert

Front 46

What route of drug entry is good for low MW, lipophilic drugs?

Back 46

The corneal route

Front 47

What route of drug entry is good for high MW, hydrophilic drugs?

Back 47

The conjunctival/scleral route

Front 48

Name the steps, from beginning to end, of drug entry via the corneal route

Back 48

1) Drug in tear fluid
2) Cornea
3) Aqueous Humor
4) Lens, Iris, Ciliary Body
5) Systemic circulation

Front 49

Name the steps, from beginning to end, of drug entry via the conjunctival/scleral route

Back 49

1) Drug in tear fluid
2) Conjunctiva
3) Sclera
4) Choroid, retina
5) Systemic circulation

Front 50

What role does the vitreous humor play in the route of drug entry?

Back 50

A small percent of the drug from the corneal route leaves the aqueous humor into the viterous humor, which then migrates to the choroid, retina

Front 51

Describe the route of drug loss from the precorneal area

Back 51

Conjunctival-Scleral Binding --> Tear Protein Binding --> Nasolacrimal Drainage

Front 52

Describe the route of drug loss from the cornea

Back 52

Drug-Protein Binding --> Enzymatic Degradation

Front 53

Describe the route of drug loss from the anterior chamber

Back 53

Drug-Protein Binding -- Enzymatic Degradation & Trebecular Network Drainage

Front 54

What routes lead to systemic drug entry?

Back 54

1) Conjunctiva and lymphatic drainage
2) Nasal cavity
3) Retinal Vasculature

Front 55

What are the challenges with regards to topical drug delivery to the eye?

Back 55

1) Limited area for drug absorption
2) Selective corneal epithelial barrier
3) Tear Clearance and Nasolacrimal Drainage
4) <5% instill drug absorbed
5) Patient compliance
6) Aging alters corneal characteristics and bioavailabilit
7) Moderate discomfort and temporary alterations of vision