Ophthalmic

Question 1

Delivery routes to the eye

Answer 1

Topical
Intravitreal
Subconjunctival
Subchordial
Suprachordial

Question 2

Topical ocular delivery goals

Answer 2

Target the site of action
Prolong residence time
Decrease frequency
Improve patient compliance

Question 3

Eye drop advantages

Answer 3

Each access and localized effect
Avoid 1st pass metabolism and system side effects

Question 4

Eye drop disadvantages

Answer 4

Efficient clearance mechanisms
Hood-occupation barriers
Posterior eye diseases harder to treat

Question 5

Barriers to topical drug delivery

Answer 5

Cornea—major barrier
Iris—melanin binds drugs
Tear duct—nasolacrimal clearance
Conjunctiva—vascular, increased clearance
Ciliary body—produces aqueous humor

Question 6

Cornea as a barrier

Answer 6

Epithelium—lipophilic
Stroma—hydrophilic

Question 7

The tear film

Answer 7

Lipid belayer—protective
Aqueous layer—anti-bacterial
Mucus layer—adherence
Protein composition influences viscosity
Blinking replaces tear film
Irritating drugs stimulate reflex blinking and faster elimination

Question 8

Nasolacrimal drainage

Answer 8

Every time you blink drugs are cleared with tears and sent to the nasal cavity

Question 9

Aqueous humor

Answer 9

Constant flow of solution clears the drug

Question 10

Vitreous humor

Answer 10

Hydrogel
Not a lot of flow, only diffusion
Excellent culture for bacteria
Poor penetration of antibiotics

Question 11

Conjunctiva

Answer 11

Drug loss via pre-corneal clearance due to large blood supply

Question 12

Choroid

Answer 12

Highly vascularized
Allows for systemic clearance through blood

Question 13

Physiological factors of drug uptake

Answer 13

Tear film and nasolacrimal drainage
Blinking
Protein binding
Metabolism and efflux
Conjunctival loss

Question 14

Formulation factors for drugs in the eye

Answer 14

Instilled volume
Drugs and adjuvants
Surface tension
Osmolality
PH
Viscosity

Question 15

Instilled volume

Answer 15

Smaller volume—>slower drainage—> increased residence time
Ideally high concentration of drug in small volume

Question 16

Drugs and adjuvants

Answer 16

Drugs can often cause corneal irritation leading to increased tear secretion
Some drugs can also decrease tear secretion

Question 17

Surface tension

Answer 17

Lower surface tension—> tear film destabilization —> reflex blinking
Lower surface tension disrupts tight junctions in the mucus layer —> increased corneal permeability

Question 18

Osmolality

Answer 18

Hypotonic—> swelling and increased permeability
Hypertonic—> loss of drug and loss of surface cells
Tears regain Osmolality in 1-2 minutes

Question 19

PH

Answer 19

Optimal 7-7.7
Acidic: reflex tears and blinking
Basic: saponification and loss of membrane integrity

Question 20

Viscosity

Answer 20

High viscosity: prolongs retention time, too much can lead to reflex tears

Question 21

To increase viscosity

Answer 21

PVA or methyl cellulose

Question 22

Ophthalmic formulations

Answer 22

Vehicles—increase viscosity and contact time
Preservatives—antimicrobial
Antioxidants—prevent product deterioration
Permeability enhancers—increased corneal penetration
Buffers—maintain pH
Tonicity adjusters—ensure isotonicity

Question 23

Benzalkonium chloride

Answer 23

Preservative for multi-use containers
Destabilizes corneal cell membranes
Increases corneal permeability

Question 24

Side effects of preservatives

Answer 24

Stinging/burning
Dry eye sensation
Tearing
Anterior blepharitis
Conjunctival follicles
Superficial punctuate keratitis

Question 25

Solution advantages

Answer 25

Easy to prepare Inexpensive Easy to use

Question 26

Solution disadvantages

Answer 26

Cannot sustain high drug concentrations

Question 27

Delivery issues with topical ocular delivery

Answer 27

Limited area of drug absorption Selective corneal epithelial barrier Tear clearance and nasolacrimal drainage Vascular clearance

Question 28

Patient issues with topical ocular delivery

Answer 28

Frequent administration Difficulties with application May temporarily affect vision

Question 29

Strategies to improve bioavailability

Answer 29

Increase tear film contact time Increase corneal permeability

Question 30

Increase tear film contact time

Answer 30

Mucoadhesive polymers

Question 31

Increased corneal permeability

Answer 31

Prodrugs Penetration enhancers Drug cyclodextrin complexes Lipid-based carriers Iontophoresis