Ophthalmic Flashcards
Delivery routes to the eye
Topical
Intravitreal
Subconjunctival
Subchordial
Suprachordial
Topical ocular delivery goals
Target the site of action
Prolong residence time
Decrease frequency
Improve patient compliance
Eye drop advantages
Each access and localized effect
Avoid 1st pass metabolism and system side effects
Eye drop disadvantages
Efficient clearance mechanisms
Hood-occupation barriers
Posterior eye diseases harder to treat
Barriers to topical drug delivery
Cornea—major barrier
Iris—melanin binds drugs
Tear duct—nasolacrimal clearance
Conjunctiva—vascular, increased clearance
Ciliary body—produces aqueous humor
Cornea as a barrier
Epithelium—lipophilic
Stroma—hydrophilic
The tear film
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
Nasolacrimal drainage
Every time you blink drugs are cleared with tears and sent to the nasal cavity
Aqueous humor
Constant flow of solution clears the drug
Vitreous humor
Hydrogel
Not a lot of flow, only diffusion
Excellent culture for bacteria
Poor penetration of antibiotics
Conjunctiva
Drug loss via pre-corneal clearance due to large blood supply
Choroid
Highly vascularized
Allows for systemic clearance through blood
Physiological factors of drug uptake
Tear film and nasolacrimal drainage
Blinking
Protein binding
Metabolism and efflux
Conjunctival loss
Formulation factors for drugs in the eye
Instilled volume
Drugs and adjuvants
Surface tension
Osmolality
PH
Viscosity
Instilled volume
Smaller volume—>slower drainage—> increased residence time
Ideally high concentration of drug in small volume
Drugs and adjuvants
Drugs can often cause corneal irritation leading to increased tear secretion
Some drugs can also decrease tear secretion
Surface tension
Lower surface tension—> tear film destabilization —> reflex blinking
Lower surface tension disrupts tight junctions in the mucus layer —> increased corneal permeability
Osmolality
Hypotonic—> swelling and increased permeability
Hypertonic—> loss of drug and loss of surface cells
Tears regain Osmolality in 1-2 minutes
PH
Optimal 7-7.7
Acidic: reflex tears and blinking
Basic: saponification and loss of membrane integrity
Viscosity
High viscosity: prolongs retention time, too much can lead to reflex tears
To increase viscosity
PVA or methyl cellulose
Ophthalmic formulations
Vehicles—increase viscosity and contact time
Preservatives—antimicrobial
Antioxidants—prevent product deterioration
Permeability enhancers—increased corneal penetration
Buffers—maintain pH
Tonicity adjusters—ensure isotonicity
Benzalkonium chloride
Preservative for multi-use containers
Destabilizes corneal cell membranes
Increases corneal permeability
Side effects of preservatives
Stinging/burning
Dry eye sensation
Tearing
Anterior blepharitis
Conjunctival follicles
Superficial punctuate keratitis
Solution advantages
Easy to prepare
Inexpensive
Easy to use
Solution disadvantages
Cannot sustain high drug concentrations
Delivery issues with topical ocular delivery
Limited area of drug absorption
Selective corneal epithelial barrier
Tear clearance and nasolacrimal drainage
Vascular clearance
Patient issues with topical ocular delivery
Frequent administration
Difficulties with application
May temporarily affect vision
Strategies to improve bioavailability
Increase tear film contact time
Increase corneal permeability
Increase tear film contact time
Mucoadhesive polymers
Increased corneal permeability
Prodrugs
Penetration enhancers
Drug cyclodextrin complexes
Lipid-based carriers
Iontophoresis
