Ocular delivery Flashcards
Parts of the eye (that i don’t know)
Conjunctiva- fleshy bit under eye
Cornea- clear membrane that covers the eye ball
Choroid- blood vessels that supplies the back of the eye
Sclera- the white of the eye
Advantages of ocular administration
Drug delivered straight to target site
Higher conc. at target site achieved than with oral forms
Lesser side effects
Relatively easy for patient to self administer
Disadvantages of ocular administration
Poor drug retention and high clearance from eye
Requires frequent dosing therefore is inconvenient for patient
Must be sterile
Ointments can cause blurring and other forms can cause local irritation
The problems of ocular administration
Blinking eye has vol of 7mcl and unblinking has vol of 30mcl
2drops of solution contains 100mcl and the removal of solution from eye is <2 mins
Due to these only around 1% of applied dose is absorbed
Conjunctiva
Made of non keratinised, stratified squamous epithelium, goblet cells and columnar epithelium
Good blood supply with relatively large SA of 18cm2 and has greater permeability than cornea.
This however means most of the drug is lost to systemic circulation
Produces and maintains tear film
The three layers of the cornea
1) Multilayer, lipid rich epithelium, 50-100 microns
2) Aqueous matrix, stroma (has collagen and keratocytes), 0.6-1mm
3) Single layer of cells, lipid rich endothelium, maintains hydration, 5 microns
Administering to cornea
Must be both oil/water soluble due to differing layers (req. intermediate logP)
Low MW drugs have better permeability
Is avascular (v. little blood flow) and slightly -vely charged
Properties of lacrimal fluid
pH=7.4 and buffers pH 3.5-10
Isotonic with blood though does not necessarily require isotonic formulations
Considerations for ocular formulations
Salt to increase solubility to increase conc for absorption (as there is no transporters on cornea, v. reliant on diffusion)
Salts can however kinda sting
Low MW with intermediate LogP and particle size should be <10microns
pH can affect shelf life of drugs
Common excipients in ocular formulations
Purified water USP
Hydrophilic polymers control flow from dispenser and increase residence on eye
Polyacrylic acid in aq. gels to treat dry eyes
Preservatives necessary to maintain sterility of multidose dispenser (eg cationic surfactants, low % parabens)
3 ways of manufacturing ocular formulations
Produce in clean conditions and autoclave
Produce in clean (or aseptic) conditions and filter
Produce under aseptic conditions (essential for suspensions)
Ocular ointments
Common for infection/inflammation
Improved retention therefore less frequent dose
Usually paraffin base or PEG/polyacrylic acid for aq. gels
Intraocular delivery examples
Anti VEGF treatment for age related macular degeneration (AMD)
Ganciclovir implant (Vitrasert) to treat cytomegalovirus retinitis
Fluocinolone implant (Retisert) to non infectious uveitis
Dexamethasone implant (Ozurdex) for macular oedema
What is the macula?
The functional center of the retina and provides the best colour vision
Hence it is of particular interest to protect
