Ocular Drug Delivery Flashcards
What are the Ocular barriers in drug delivery
Poor permeability in the cornea
Nasolacrimal drainage
Tear reflex
Blinking
Non-corneal absorption
What is the corneal barrier and how does it have this barrier, give an example
Corneal is relatively impermeable compared to other tissues
Hydrophobic tissue: 90% barrier to hydrophilic drugs and 10% hydrophobic drugs
Stroma: hydrophilic tissue, barrier to hydrophobic drug
Enzymes: esterases, petidases, proteases include cornea
If the pH is lower than 4 or higher than 10 in the eye, what can that lead to ?
Copious lacrimation and damage
What is non corneal absorption and where is this route important in
- The penetration of conjunctiva and underlaying sclera into the vitreous humour
- Route important for:
Hydrophilic molecules and large molecules- due to cornea being relatively impermeable to hydrophilic drugs
Describe the approach to optimise topical ocular delivery through proper placement of eye drops
- Drop placed in inferior cul-de-sac through gently pulling lower eye lid- create pouch
- Small amount of liquid is then entrapped into inferior conjunctival sac- where retained twice as long
- This is compared to superior sclera
Describe the approach to optimise topical ocular delivery through reducing instilled eye drop dose
Optimal value: 8-15 micro litres
Typical amount per eye drop: 35 to 56 micro litres: value is too high as eyes can only retain certain amount
Describe the approach to optimise topical ocular delivery through formulation approaches
- Modify integrity of corneal epithelium through chelating agent and surfactant use
- Modify chemical structure using pro-drug approach- drug becomes hydrophobic due to enzymes in eye
Give an example of adrenaline as a pro drug
Dipivoyl epinephrine converted to epinephrine
Give an example of a prodrug used in the eye and its role
- Latanoprost: used to control intraocular pressure which can control progression of glaucoma and ocular hypertension
- Inactive: until hydrolysed by esterase in the cornea
What are the formulation approaches to improve pre-corneal retention
- Viscous systems: poly vinyl alcohol, hydroxyethyl cellulose
- Muco-adhesives: carbopols, carbomers
- Phase transition systems: insitu gelling systems
- Changes in pH (cellulose acetate phthalate and carbomer solutions will make gel when in contact with tear fluid pH = 7.4
- Changes in temperature
Give an example of a commercial in situ gelling product
Fucithalmic viscous eye drops:
Fusidic acid 1% w/w
Benzalkonium chloride
Disodium edetate
Give examples of the materials that make up contact lenses
- Polymethylmetacrylate (PMMA): provides opportunity to use other materials
- Contact lenses: Hard or soft lenses according to modulators of elasticity
- Examples: Hydrogels or silicone based elastomers
How do you improve the performance of medicated contact lenses
PHEMA: hydrogel coating
PLGA: poly lactic acid coglycolic acid film
Zero order kinetics
Therapeutically relevant connotations of up to 1 month
What are ocular inserts and give an example of a drug used in this way
- An insoluble device that is formed of two semi permeable membranes that contains a drug Example: pilocarpine
- Drug diffuses over period of 7 days
- Results: Decreased intraocular pressure that is achieved in patients with hypertensive open angled glaucoma
How are Mydriasert containing 0.28mg Tropicamide and 5.4mg of phenylephrine hydrochloride used
Ophthalmic insert
What other intraocular drug delivery methods are there
Intravitreal injections
Liposomes
Micro-particulates and nano-particulates
Intraocular devices (implants)
Iontophoresis
Describe intravitreal injections use and the problems that may occur from this
- Direct injection of drug into the vitreous cavity to achieve higher drug concentrations
- Half life of drugs: shorter
- Repeated injections: necessary to maintain drug at effective therapeutic level over time
- Problems: repeat injections lead to vitreous haemorrhage, infections, lens or retinal injury
What is Ozurdex and its use
- Sustained release biodegradable implant: contains steroid dexamethasone
- Indication: macular oedema inflammation of the posterior segment of the eye presenting as non infectious uveitis
What is iontophoresis
Non invasive technique used to allow drugs to diffuse through the impermeable cornea
Drug is carried via positive electrode which carries positive drug into the tissue and ground electrode
