L3: Ocular delivery systems Flashcards
What are SIX routes of ocular administration?
Topical (99% of all drugs)
Intracameral (into anterior chamber, usually only after cataract surgery)
Intravitreal
Periocular (not into eye)
Suprachoroidal
Systemic (only 1% enters eye, so not very direct)
What are THREE transport barriers in the eye?
Tear film
Cornea
Blood-retina barrier
What are THREE drug characteristics to consider in absorption?
logP
pKa
Molecular weight
What are FOUR advantages of topical ocular delivery?
REDS
Rapid onset of action
Ease of application
Direct application to target site
Smaller drug dose required
What are FIVE disadvantages of topical ocular delivery?
Contamination of drops
Preservative may be needed –> may be added but can causes irritation eg. benzalkonium chloride
Limited penetration
Fast elimination
Systemic absorption –> side effects. Not effective for choroidal/back of eye infections
What is the cornea transport barrier?
Only small & lipophilic drugs can pass
Epithelium, stroma, endothelium
Lipophilic, hydrophilic, lipophilic
What are ocular solutions?
Homogeneous mixture composed of only one phase
Solute dissolved in solvent
eg. BBs, PGAs, AAs, CAIs, some antibiotics
What are THREE advantages of ocular solutions?
Good stability
Easy to prepare
Low cost
What are THREE disadvantages of ocular solutions?
Fast drainage –> does not last long on eye surface
Low drug permeability –> no concentration gradient since drop does not last long on eye surface
Low drug bioavailability –> due to corneal barrier
What are ocular suspensions?
Heterogeneous mixture composed of two phases
Solid phase dispersed through liquid base
eg. steroids
What are TWO advantages of ocular suspensions?
Longer retention time –> higher drug bioavailability
Reduced drainage –> drug remains in eye for longer
What are THREE disadvantages of ocular suspensions?
Sterilisation may cause physical instability
Particle size not <5 –> foreign body sensation –> reflex tearing
Particle aggregation/sedimentation –> must be shaken before use
What are ocular ointments?
Semisolid preparation intended for external application
Drug in hydrocarbon base (no water)
What are THREE advantages of ocular ointments?
High viscosity –> reduced drainage –> more likely absorbed
No stinging upon application –> eye drops stinging usually due to differences in pH
Oily base
- No dilution by tears
- No preservative required to prevent microbial growth
- Suitable for moisture sensitive drugs
- Lubrication
What are TWO disadvantages of ocular ointments?
Blurred vision –> application only at night
Greasy –> discomfort/irritation –> reflex tearing
What are ocular emulsions?
Heterogeneous mixture of two immiscible phases
Contains water, oil, surfactants/preservative –> caution irritation
What are TWO advantages of ocular emulsions?
Suitable for oil-soluble drugs
Lubrication
What are THREE disadvantages of ocular emulsions?
Surfactant –> irritation, local toxicity
Low stability –> flocculation leading to cracking, therefore dose not reliable
High cost
What are FIVE formulation considerations?
POVIB
Physicochemical drug properties
- Concentration
- Lipophilicity
- pH
- Molecular weight
- pKa
Osmotic pressure within 310-350 mOsm/kg
Viscosity –> allows drop to remain in eye longer for concentration gradient
Instillation volume –> eye max. 30 microlitres
Buffer capacity & pH –> best between pH7 - 7.7
How does drug activation work? (metabolism)
eg. Prostaglandin analogues
Ester prodrugs –> more lipophilic –> crosses corneal epithelium more readily –> activation by esterases into active drug molecule
How are drugs eliminated from the eye?
Nasolacrimal drainage –> also plug inner corner of eye to avoid systemic absorption & side effects
How to administer eye drops that improves ocular bioavailability
Shake bottle before use (suspensions)
Apply one drop at a time, close eyes & block nasolacrimal duct
Wait 5 mins before next drop –> avoid washout effect for higher absorption
What delivery systems improve ocular bioavailability?
Corneal penetration enhancers, prodrugs –> improve absorption
Viscosity enhancers, lubricating agents –> prolong concentration gradient
In situ gelling of novel eye drops can be induced by…
Higher temperature in eye
Ions in tear fluid
pH of tear fluid
The principle behind ocular iontophoresis is…
“like repels like”
Electrorepulsion “pushes” drug into tissue
