Ocular Route Flashcards
What are tears produced by?
Lacrimal gland
What does the pre-corneal tear film do?
Lubricates + protects eye surface
What are the 3 layers in eye?
Superficial lipid layer
Central aq layer
Inner mucus layer
What does the superficial lipid layer do?
Reduce evaporation rate of tears
What does the inner mucus layer do?
Allows spread of tear film over eye surface on blinking
What is the pH of normal tears?
7.3-7.7
When is pH of the tears lowest?
On awakening
What can pH of tears vary from + why?
5.2-9.3 depending on age + disease
What are buffer capacity of tears determined by?
Bicarbonate ions
Proteins
Mucins
Why are tears more acidic in contact-lens wearers?
Impediment influx of CO2
When are tears more alkaline in case of disease?
Dry eye
Severe ocular rosacea
Lacrimal stenosis
What is the normal tear vol?
5.9 micro L
What is the max fluid vol in lower eyelid sack?
25-30 micro L
What is the rate of basal tear secretion?
1.2 micro L/min
What happens when eye drops are administrated?
Tear vol increases
= rapid reflex blinking
What is blinking?
Defence mechanism of eye
Why is brisk blinking reflex important?
Fast enough to proceed high-speed foreign bodies approaching eye
What does blinking activate?
Pumping mechanism for drainage of tears through lacrimal drainage apparatus
What is the blink rate?
17 per min
1 blink every 3.5s
What are the different ocular delivery routes?
Cornea
Periocular
Intravitreal
Describe cornea route
Main route for topically administered drugs to reach aq humour
Describe periocular route
By pass conjunctival + corneal epithelium
Describe intravitreal route
Directly reach back of eye
What are the barriers to ocular delivery?
Lachrymal (tear) system constantly washes eye
Blinking promotes fluid clearance
Max dose vol = 20-30 micro L
How long will effective clearance take to clear eye drops?
4-23 minutes
What are the elimination routes?
Aq humour into systemic uveoscleral circulation
Outflow through trabecular meshwork + Schlemm’s canal
Vitreous humour via diffusion into anterior chamber
Posterior route across blood retinal barrier
What must topical ocular preparations be?
Isotonic Close to neutral pH Stable Sterile Particle free
If a topical ocular preparation is multi-dose what must it contain?
Preservative
What are the advantages of topical ocular preparations?
Easy for patient to use on their own
Rapid onset of action
Avoid hepatic metabolism
What must all ophthalmic preparations be?
Sterile
Why must they be sterile?
Ocular infections = vision loss
When can preservatives not be used?
Intraocular products
Which preservative is often used?
Benzalkonium chloride
Why have single dose units been developed?
To avoid the use of preservatives whilst maintaining product stability
What is problem with single dose units?
High manufacturing + packaging costs
What determines osmolarity?
Salt conc within lacrimal fluid
What do dry eye patients have?
Hypertonic lacrimal fluid
What do hypotonic solutions cause?
Oedema
What do hypertonic solutions cause?
Dehydration
What do hypotonic + hypertonic solutions both cause?
Irritation + induce tear production
= clears any applied solution
What ocular solution is tolerated well?
Osmotic pressure equal to 0.6-2% NaCl
What may be added to achieve isotonic solution?
Tonicity agents
What is the buffer capacity of lacrimal fluid?
Low
What is an acceptable pH for solution?
3.5 - 9
What happens if an agent is unstable at neutral pH?
Formulated at pH 4.5 as compromise
What are commonly used buffers?
Borate + phosphate
What is the lacrimal fluid tension?
43.6-46.6 mN/m at 37 degrees
What can happen if a solution has a lower surface tension?
Destabilise tear film + disperse lipid layer into droplets
= affect evaporation = irritation
Why are surfactants included?
Solubilise or disperse drugs
What happens to irritation potential down surfactant list? Cationic Anionic Zwitterionic Non-ionic
Decrease
What happens when you increase viscosity of solutions?
Prolong residence time = enhance drug absorption
What are examples of H2O-soluble polymers?
Hydroxypropylmethylcellulose
Polyvinyl alcohol
Polyethylene glycol
What happens if over viscosity limit?
Cause pain
What happens if very viscous solution?
Blurring
May block puncti + lacrimal canals
What are most ophthalmic preparations?
Solutions
What is design of solution?
Eye drop bottle = cheap to manufacture
Why are solutions homogenous?
Better dose uniformity
What is typical dose vol for solutions?
25-50 micro L
What is problem with solutions?
Cleared by drainage
What do ointments do?
Reduce clearance from eye
What are release profiles of ointments?
2-4 hrs
What can ointments be used for?
Poorly soluble drugs
What bases are used for the ointments?
Hydrophobic - paraffins
Hydrophilic - PEG
What are ointments used for?
Antibiotics
Antifungals
Steroids
What is problem with ointments?
May cause blurring
Describe gels
Semi-solid, H2O-soluble bases
More suitable than ointments for H2O-soluble drugs
Use polymers dispersed in liquid
What polymers do gels use?
OVA
Poloxamer
Describe ion-exchange resin
Drug ionically bound to an ion-exchange resin to form insoluble complex
How is drug released in ion-exchange resin?
Drug released from complex through exchange of drug ions in tear fluid
What factor in ion-exchange resin control rate of dug release?
Resin particle size
What are formulations?
Solutions
Ointments
Gels
Ion-exchange resin
