Ocular Systems Flashcards
Name the 9 eye diseases?
Allergies Blepharitis Age-related macular degeneration (AMD) Uveitis Conjunctivitis (pink eye) Dry eyes Cataract Diabetic eye disease Glaucoma
Describe uveitis.
Inflammation of middle layer of the eye causing pain and changes to vision. May cause glaucoma and cataracts.
Infoooo
Cornea is made of 3 distinct layers so the drug must possess certain physicochemical properties so that the drug can permeate across membranes into the aqueous humour.
What two layers must the periocular injection pass to reach retina layer?
Sclera - white portion of eye
Choroid - where blood flow occurs - supplies nutrients
What is intravitreal injection?
Injection straight into eyeball.
What are 5 physiological barriers of the eye?
Tear production/blinking Cornea Sclera Protein binding Drug metabolism
What is the action of mydriatics and cycloplegics? Name two drugs and the dosage forms available.
Dilation of pupils for the examination of fundus of the eye.
Tropicamide and Cyclopentolate.
Eye drops, eye ointment.
What is the action of beta blockers for the eye? Name two drugs and the dosage forms available.
Reduce aqueous humour production to lower intraocular pressure in treatment of glaucoma and for ocular hypertension.
Timolol and Betaxolol.
Eye drops, suspension, gel-forming solution.
How are drugs transported across the cornea for topically applied drugs?
- Passive diffusion along concentration gradient, paracellularly or transcellularly across the cornea.
- Carrier-mediated active transport.
What is the Log P value of an effective drug?
Log P = 2-3
Better efficacy, therapeutic effects and so less frequency of dose required.
What does the fraction of unionised drug vs ionised drug depend on?
pKa of the drug
pH of eyedrops and lachrymal fluid
(lachrymal fluid dilutes drug)
Corneal charge and drugs.
Corneal epithelium is NEGATIVELY CHARGED - hence charged cationic drugs permeate more easily through cornea than anionic drugs.
What should the size of the molecules be to allow easier transport across the cornea?
500 daltons.
When physicochemical properties of the drug are not considered optimum to reach the site of action in the eye, what can be done?
Use a prodrug.
Prodrug enzymatically/ metabolically/ chemicals is converted to the parent drug which has therapeutic effects.
What are the 4 routes of administration of drug into the eyes?
- Systemic (parenteral)
- Oral tablets etc
- Periocular/intravitreal injection
- Topical - eyedrops
What are the issues in using systemic route for administration into the eye?
Only small amount of drug reaching site due to poor bioavailability and solubility.
Poor penetration of drug.
Dilution occurs hence large doses administered - cause toxic side effects.
What is an issue with periocular injections?
Needle phobia.
What are the two parts of eyes called?
Anterior - front
Posterior - back
What are the three layers that the cornea is made from? State whether they are hydrophobic/philic.
Epithelium - hydrophobic
Endothelium - hydrophobic
Stroma - hydrophilic
What causes loss of product when topical drugs are applied to eyes?
Eye drops removal rapid due to tears and blinking. Tear production occurs due to change of pH of eye caused by drug.
What is the action of miotics? Name two drugs and the dosage forms available.
Constriction of pupil for treatment of glaucoma.
Pilocarpine and Carbochol.
Eyedrops, viscous eyedrops, ocular insert, gel.
What is the action of local anaesthetics for the eye? Name two drugs and the dosage forms available.
Irreversibly blocks pain receptors. Used in tonometry and before minor surgery.
Oxybuprocaine and Amethocaine.
Eyedrop solution.
Some drugs are use for diagnostic purposes. Name the drug, its action and dosage form available.
Fluorescein sodium colours the eye to aid in locating areas of damage.
Eye drops.
What is tonometry?
Device placed on cornea of eye to measure pressure.
Sometimes artificial tear preparations are used for eye lubrication. Name the drug, its clinical use and dosage forms available.
Hypromellose polyacrylic acid to treat tear deficiency.
Eye drops, viscous eye drops, gel.
What are 4 physicochemical properties that affect the rate and route of permeation into the cornea?
Solubility - hydrophilicity/lipophilicity.
Molecular size and shape.
Charge.
Degree of Ionisation.
Describe paracellular and transcellular passive diffusion.
Paracellular diffusion is between cells (through intercellular spaces) - for hydrophilic drugs.
Transcellular diffusion is through the cells - for hydrophobic drugs.
Drugs with both properties - permeate efficiently.
Define bioavailability.
Bioavailability is the rate and fraction of drug administered which successfully reaches site of action.
What is a prodrug as eye medication?
Drug administered into the eye - crosses the barrier and converts to its active form via enzymatic breakdown of the molecule.
What is the benefit of using prodrug for eye?
Increases BIOAVAILABILITY, POTENCY, SOLUBILITY and STABILITY with decreased side effects.
(enhance drug levels in eye - better therapeutic outcome).
List the 5 formulations/preparations available for treatment of eyes.
Solutions Suspensions Ointments Water-Based Gels Ocular Insert
What are the 4 advantages of using solution preparations?
- Solutions mainly have water soluble compounds.
- High solution concentration can be achieved due to high solubility.
- Easy to manufacture.
- Better dose uniformity and ocular bioavailability.
What is the disadvantage of using eye drop SOLUTIONS?
Rapidly drained from eye.
What can be done to decrease drainage from eyes when using solution eydrops?
Incorporate viscosity-increasing agents in solutions = increase tear viscosity and lowers drainage - drug retained in eyes for longer.
(High viscosity products - not well tolerated by eye.)
What range of viscosity must be used?
10cP to 25cP.
Describe water-based gels as ophthalmic formulations.
These are preparations containing polymers that are liquid formulations upon administration but a gel on contact with eye allowing drug to be retained for longer.
List the reasons why there would be a phase change from liquid to semi-solid in water-based gel preparations.
- change in pH
- change in temperature
- change in ionic strength of tear film
What are the advantages of using gels?
- As drug will be retained for longer by gel, frequency of doses will be lower.
- Improved patient compliance - in situ gelling process of timolol.
- Ease of administration.
Describe suspension ophthalmic preparations.
Aqueous or oily suspension eye-drop formulations may be considered for drugs that are poorly water soluble, or because of poor aqueous drug stability.
Drug particle size must be <10mcgm
What are the advantages of using suspensions?
- Prolong drug retention in eye.
- Drug retention in tears (particles dissolves slowly)
- Improves ocular bioavailability.
What are the disadvantages of ophthalmic preparations?
Pose a physical stability problem.
- dose uniformity
- increase in particle size with time
- difficult to manufacture in sterile conditions
Describe ophthalmic ointments preparations.
Semi-solid preparations intended for application in the conjunctiva.
What are advantages of ointments?
- Increased drug contact time - allows drug to permeate across cornea.
- Better bioavailability.
What is disadvantage of ointments?
Messy
Night-time application as it can cause blurred vision
- hence poor patient compliance
What are the 5 packaging design criteria?
- Materials are compatible with the formulation and ensure product stability
- Sterility of the product can be achieved & assured for the entire shelf-life
- Materials meet pharmacopoeial and regulatory standard requirements
- Containers should be tamper-evident &
- Pack design offers ease of administration to the patient.
What are the two requirements for ophthalmic drugs to be accepted?
- Must be sterile up to the point of use.
2. Must comply with pharmacopoeial tests for sterility.
What are established excipients/agents? What is the positive effect of this?
Established excipients = already approved and tested excipients - makes process easier.
- improves patients tolerability.
- improves patient compliance.
What factors to consider when ocular solution-based product is to be made? (5)
Solubility Osmolarity Vehicle viscosity Stabilizers Antimicrobial preservatives
Why might excipient, bio-adhesive agents be used?
Added if we want drug to be retained by eye for prolonged period of time to enhance permeation of drrg - can reduce frequency of dosage.
Many drugs are weak bases or acids and can be formulated as water-soluble, pharmaceutically acceptable salts. What determines the choice of salt type to include in water soluble solution formulations?
Solubility
- optimum solubility will increase the retention of of the therapeutic agent in the precorneal region - allows to reach maximum pharmacological effect.
- concentration of drug in ocular agents should be high.
What is the issue in using certain drug salts?
Results in pain and irritation.
What range of pH values can the eye tolerate?
pH 3.5-9.0
How does pH affect antimicrobial preservatives and parabens?
These become inactive at high/alkaline pH. More active in acidic pH.
How are acrylic acid polymers - carbomer/brand: Carbochol sensitive to pH?
The pH within the formulation is pH4-5. The increase in pH when applied to eye causes formulation to turn to gel.
What two chemical are used for acidic pH adjustements?
citric acid/sodium citrate
acetic acid/sodium acetate
What two chemicals are used for alkaline buffer adjustments?
phosphate buffers
borate buffers
If pH manipulation fails to increase the drug solubility sufficiently, what can be done?
Give 3 examples of these materials?
Add solubility-enhancing materials to the formulation
- polyethylene glycols, propylene glycols, polyvinyl alcohol, poloxamer, glycerin, cellulose derivatives, surfactants.
If desired aqueous solubility is not achieved even after using solubility enhancing materials, what can be done?
Consider oily solution/emulsion.
What range of tonicity is tolerated by the eye?
Tonicity is a measure is a measure of the effective osmotic pressure gradient
0.5-1.5% NaCl equivalents
Ideal = 0.9% NaCl (0.9%w/v)
What is a poloxamer?
A temperature-sensitive polymer - liquid in formulation but turns viscous when applied to eye.
Give 5 examples of ophthalmic solutions or suspensions?
Dextrose, NaCl, KCl, buffering salts, glycerol.
Describe vehicle viscosity.
Increase in vehicle viscosity = increase in retention time of drug in eye.
Very high vehicle viscosity is not tolerated by the eye. Drug diffusion is inhibited and difficult application.
Irritation to eye.
List 5 FDA approved viscosity enhancing agents.
Methylcellulose Hydroxypropyl cellulose Polyvinyl alcohol Carbomer Polyethylene glycol
How to prevent oxidative degradation f drugs?
Add antioxidants or chelating agents.
What is the issue with using plastic bottles to store ophthalmic solutions?
Gases permeate through container - susceptible to oxidative degradation.
Name 5 commonly used antioxidants.
Sodium bisulphite Sodium sulphite 8-hydroxyquinolone Ascorbic acid acetylcysteine Antipyrine
What 5 features should antimicrobial preservatives possess?
- Must be effective at the formulation pH.
- Must be stable to processing.
- Must be heat stable (for sterilisation).
- Must be stable over the product shelf-life
- Inert - no interaction with agents or packing material.
Name 3 regulatory approved antimicrobial preservatives.
Benzalkonium chloride Chlorhexidine Methylparaben Phenylmercuric borate Thimerosal
Production under clean conditions must be done. What 3 ways are eye products made?
Autoclaving
Filtration
Production under aseptic conditions
Describe autoclaving.
Product is manufactured and packaged in the final container under clean conditions.
- sterilisation performed under most-heat sterilisation.
Describe filtration.
Filtration through an appropriate filter followed by sterilsation filtration and packaging.
Describe production under aseptic conditions.
Dispersion of the sterile therapeutic agents into a sterile vehicle and packaging, all done under aseptic conditions.
Certain agents can be added into formulations for patients with damaged cornea due to burns/accidents. Explain this and describe the problem with this.
To regenerate corneal tissue, growth factors and proteins can be added to the formulation.
Problem - proteins and growth factors cannot stand thermal sterilisation as they will be denatures.
This formulations must be made under aseptic conditions.
What test can be done to establish if there compatibility problems between drug, excipient and packaging?
Accelerated stress stability testing
What are contact lenses?
Contact lenses are eye-shaped thin discs of polymer(s), designed to correct vision problems arising from refractive error.
What are the 4 types of contact lenses available?
Hard lens
Semi-hard/ semi-flexible lens
Soft lens
Soft continuous wear lens
Describe hard lenses (6).
- Made from hydrophobic polymer such as poly(methyl methacrylate) (PMMA)
- Absorb 1-2% water
- Cheap
- Long-lasting
- Give excellent vision correction
- Comfort and tolerance levels quite low
Describe semi-hard/semi-flexible lenses (6).
• Made from hydrophobic gas-permeable polymer such as cellulose acetate
butyrate (CAB)
• Low water content
• Semi-flexible
• Long-lasting
• Give good vision correction
• Permit passage of oxygen through lens to cornea - prevents suffocation of cornea
Describe soft lenses (6).
- Made from hydrophilic polymer such as poly(hydroxyethyl methacrylate) (pHEMA)
- Contain 50-80% water
- Flexible
- Used for 1 day – 1 month
- Give good vision correction
- Comfort and tolerance levels very high
Describe soft continuous wear lenses (7).
- Made from hybrid hydrogel-silicone material
- Lower water content than hydrogel lens (~33%)
- Flexible
- Long-lasting (1 month)
- Give good vision correction
- Require no cleaning or periodic cleaning
- Permit passage of oxygen through lens to cornea.
What 5 agents are included in the formulation if a contact lens solution?
❖ Viscosity increasers – allows comfort, convenience
❖ Surfactants – allows wetting, cleaning (removes debris)
❖ Inorganic salts – isotonicity, pH, lens stability, buffering
❖ Preservative systems – efficacy, compatibility
❖ Potentiators – sequestering agents such as disodium edetate
