Routes of Administration - Ocular Flashcards
What does the outer layer of the eyes consists of?
Sclera - posterior 5/6ths of the eye
Cornea - anterior 1/6th of the eye
Describe the structure of the sclera?
- Tough, fibrous tissue
- Protects eye and maintains shape
- Front of the sclera is the ‘white of the eye’ covered by the conjunctiva and lacrimal tears
Describe the cornea.
- Positioned in front of iris and pupil
- Has extensive sensory nerves
- Avascular perfused by anterior ciliary arteries
- The surface is covered by tears from the lacrimal gland
State the 3 chambers the eyes consist of?
- Anterior chamber
- Posterior chamber
- Vitreous chamber
What does the anterior chamber and posterior chamber contain?
- Filled with aqueous humour: colourless with electrolytes, growth factors, proteins
What happens if drainage from the eyes is blocked in the anterior and posterior chamber?
Fluid and pressure accumulate leading to glaucoma
What does the vitreous chamber contain?
Vitreous humour: hydrogel, collagen fibrils and hyaluronic acid
- Proteins
- Inorganic salts
- Glucose
- Ascorbate
What is the function of the pre-corneal tear film?
- Lubricates and protects the eye surface
State the three layers which make up the pre-corneal tear film.
- A superficial lipid layer
- A central aqueous layer
- An inner mucus layer
What is the superficial lipid layer composed of and what is its function?
- Composed of sterol esters, wax, esters and fatty acid s
- Reduce evaporation rate of tears
What does the central aqueous layer consist of?
- Electrolytes
- Proteins
- Glycoproteins
- Biopolymers
- Glucose
- Urea
State the function of the inner mucus layer.
Allows spread of tear film over the eye surface on blinking
What is the buffer capacity of the tears determined by?
- bicarbonate ions, proteins and mucins
Why are tears more acidic for contact-lens wearers?
Due to impediment of the efflux of carbon dioxide
In which cases are tears more alkaline?
- In the case of diseases such as dry eye, sever ocular rosacea and lacrimal stenosis
Why is blinking important for humans?
- It is an important defence mechanism of the eye
- brisk blinking reflex is fast enough to precede high-speed foreign bodies approaching the eye
- Essential for the periodic reforming of the tear film
What does blinking activate?
- A pumping mechanism for the drainage of tears through the lacrimal drainage apparatus
State the ocular drug delivery routes.
- Cornea - main route for topical to reach aqueous humour
- Periocular delivery - bypass the conjunctival and corneal epithelium
- Intravitreal delivery - directly reach the back of the eye
What challenges does the eye present for effective drug delivery?
- The lachrymal (tear) system continually washes the eye.
- Blinking also promotes fluid clearance.
Which routes is ocular drug delivery eliminated?
- Elimination from aqueous humour into systemic
uveoscleral circulation. - Outflow through the trabecular meshwork and
Schlemm’s canal. - Eliminate from the vitreous humour via diffusion into
the anterior chamber. - Clearance via posterior route across blood retinal
barrier.
What must eye solutions be?
- Isotonic
- Close to neutral pH
- Stable
- Sterile
- Particle free
- Contain preservatives if multi-dose container
- Easy for patient to administer on their own
- Can provide rapid onset of action
- Avoid hepatic metabolism
Why must ophthalmic preparation be sterile?
- Ocular infections can rapidly lead to vision loss
Why are preservatives included in multi-dose containers?
- Inhibit microbial growth
- Cannot be used in intraocular products
- Benzalkonium chloride is often used
What determines osmolality?
Salt conc. within the lacrimal fluid - dry eye patients have hypertonic lacrimal fluid
What do both hypotonic and hypertonic solutions cause?
- both cause irritation and induce tear production - clears any applied solution
What is the acceptable pH range for ocular solution?
3.5 to 9 - at extreme pH could damage ocular tissue
What does pH control of ionisation also affect?
Aqueous solubility and membrane permeability
What happens if an ophthalmic solution has a lower surface tension?
Can destabilise the tear film and disperse the liquid layer into droplets - this can affect evaporation and lead to irritation
What happens if we increase the viscosity of solutions?
- Can prolong their residence time thus enhance drug absorption
What happens to the eye as a result of exceeding the viscosity limit?
- Over the viscosity limit, i.e. a higher force (over 0.9N) is required for blinking, would cause pain.
- Very viscous solution can cause blurring and may block the puncti and lacrimal canals.
What are the advantages of solutions?
- Simple designs: cheap to manufacture
- Solutions are homogenous - better dose uniformity
What are the disadvantages of solutions?
- Are rapidly cleared by drainage: can add viscosity modifiers
What are ointments used for?
- Reduce clearance from the eyes
- Can be used for poorly soluble drugs
- Used for antibiotics, antifungals and steroids
What may ointments cause?
Blurring
In what case would gels be more suitable than ointments?
As semi-solid, water-soluble bases so more suitable for water-soluble drugs
Describe ion-exchange resins.
- The drug is ionically bound to an ion-exchange resin to form an insoluble complex.
- Drug is released from the complex through exchange of the drug ions with ions in tear fluids.
- The resin particle size is one of the factors that controls the rate of drug release.
What are intraocular implants?
- Controlled drug delivery systems prepared from biodegradable or non-biodegradable polymers
How are ocular implants introduced?
- Introduced into the vitreous through an incision in the ocular pars plane, which is located posterior to the lens and anterior to the retina
What is biodegradable intravitreal impkant used to treat?
- Treatment of macular oedema and noninfectious uveitis affecting the posterior segment of the eye
How are intravitreal injections administered?
- By injecting a drug solution, suspension or intraocular implants into the vitreous cavity
- Main route to deliver macromolecules to the posterior segment into the eye
- Has become the gold standard treatment for many retinal diseases
