DDS: Intraocular Flashcards
What is the principal route for local ophthalmic drug delivery?
topical application of solutions to the surface of the eye as drops: easy to apply and good patient acceptance
What are the limitations of eye drops to the surface to the eye?
- Significant barrier to solute flux provided by the corneal epithelium
- Precorneal drug loss that occurs by way of tear drainage and tear fluid turnover
- < 5% of a topically applied drug actually permeates the cornea and eventually reaches intraocular tissues
What are the problems associated with ophthalmic drug delivery?
- Dilution by the lacrimal fluid (tear), aided by the mixing action of the blinking reflex
- Low permeability of the corneal tissue. Low bioavailability (0.2-2%)
- Loss through the lacrimal duct or by rolling down the side of the face.
What is the physiology of the eye?
- Cornea is avascular and transparent
- Conjunctiva provides protection and lubrication
- Cornea is multilayered with lipophilic and hydrophilic properties
- Corneal epithelium is predominantly lipophilic –> 90% resistance to hydrophilic drug transport
- Cornea nourished by aqueous humour and cleansed/lubricated by mucus and tear fluid
> Vascular network around back of eye provides metabolic support to retina, ciliary body and iris
> These membranes also provide ‘blood-eye barrier’ or blood-retina barrier (BRB)
Retina: light sensitive region that links via the optic nerve to the visual cortex
Aqueous humour: clear aqueous fluid similar to blood plasma
- Iris controls intensity of light entering the eye
Define the following periocular disorders;
Blepharitis
Conjunctivitis
Dry eye
Trachoma
Keratitis
Cataract:
Fuchs Endothelial Dystrophy:
Keratoconus:
Iridocorneal Endothelial Syndrome:
Retinitis Pigmentosa
Macular Degeneration
Diabetic Macular Oedema
Blepharitis: common and often recurring inflammatory condition causing infection of the eyelids. Symptoms: red, swollen, crusty eyelids
Conjunctivitis: “pink eye” - inflammation of the conjunctiva, caused by allergenic response or bacterial infection. Symptoms: pain, burning, scratchiness, or itchiness may occur
Dry eye
Trachoma: contagious infection of Chlamydia trachomatis. Causes a roughening of the inner surface of the eyelids - leads to pain in the eyes, breakdown of the cornea and blindness.
Keratitis: inflammatory corneal disorder due to injury, infection. Symptoms: excessive tearing, pain, photophobia, gritty sensation, inflammation
Cataract: changes in the crystalline lens causing reduced transparency – commonly due to ageing
Fuchs Endothelial Dystrophy: slowly progressing oedema of the cornea – stroma becomes cloudy
Keratoconus: progressive thinning of the cornea – blurring and shortsightedness
Iridocorneal Endothelial Syndrome: changes to the endothelium, iris, swelling of the cornea and associated development of glaucoma •
Retinitis Pigmentosa: hereditary disease with degradation of photoreceptor cells
Macular Degeneration: leading cause of blindness in ageing population. Neovascularisation or ischemia affects the retina and retinal pigmented epithelium leading to severe vision loss
Diabetic Macular Oedema: retina inflamed and swollen, can detach
What are the negatives for the following drug delivery strategies for the ye:
A) systemic
B) eye drops
C) photodynamic therapy
D) injectable solutions
A)
- limited penetration
- high drug levels = toxic
B)
- limited pentetration (less than 1%)
- rapidly diluted
- tear washout
- poor patient compliance
C)
- limited applications
- repeat procedures
D)
- rapidly diluted
- repeat procedures
What are some of the duration of action of the ocular drug delivery systems?
Fprmulation strategies to improve drug solubility, increased loading and improved bioavailability. What are some of these strategies?
- Retention of drugs improved by viscosity enhancing (polymers such as cellulose derivatives, PVA, hyaluronic acid, dextran, gellan gum) or mucoadhesive agents (interfacial interaction of polymeric-based formulation with mucosal tissue)
- Drug transport improved by penetration enhancing compounds, pro-drugs e.g. latanoprost (Xalantan™)
> Ester prodrug that is absorbed well through the cornea and completely hydrolysed to the active latanoprost acid –> for management of glaucoma
Enhanced retention: sol-gel systems
Sol-gel phase transition systems can be designed to respond to? Provide three different reasons.
- Temperature: dosage transforms from liquid at room temperature to a mucoadhesive gel at the temperature of the eye, ~34 ºC.
- pH: sol-gel transformation takes place when the dosage responds to the pH environment of the tear film, mean pH = 7.4.
- Ion response: sol-gel transformation responds to ion concentration of the tear film
name of products: azasite, virgan, cytoryn
What are THREE examples of eye formulations
- Timolol-XE® –> non-selective beta adrenergic receptor blocking agent –> gel forming solution
- Azasite® –> azithromycin ophthalmic solution
- Betoptic S –> betaxolol hydrochloride –> cardioselective beta adrenergic receptor inhibtor –> opthalmic suspension
Enhanced retention: Ocular insert dosage forms –> preparations with a solid or semi-solid consistency, whose size and shape are specially designed for ophthalmic application. What are some key design considerations?
- Comfort
- Lack of expulsion during wear
- Ease of handling and insertion
- Noninterference with vision and oxygen permeability
- Reproducibility of release kinetics
- Applicability to a variety of drugs
- Sterility
- Stability
- Ease of manufacture
What are some properties of an erodible ocular insert? What happens if there is a missing insert?
- No need to remove upon completion of therapy
- Often made of collagen or chitosan
- Hydrolytic degradation, rather than enzymatic degradation, is preferred
- Variability of patients’ tear turnover and variable interpatient insert degradation
Missing insert
> patient doesn’t know if there is a missing insert, could be fully dissolved or insert fallen out.
> potential under and over dosing
What is an example of ocular insert?
ACRISERT (hydroxypropyl cellulose ophthalmic insert) is a sterile, translucent, rod-shaped, water soluble, preservative-free, slow-release, lubricant which is placed into the inferior cul-de-sac of the eye
- One insert per day provides continuous lubrication
What are some advantages and disadvantages of non-erodible ocular insert?
Advantages
- A patient knows if the non-erodible insert is lost and needs to be replaced
- More consistent control of drug release
- Drug-polymer physicochemical interactions manipulation allows controlled release.
Disadvantages
- Possibility of discomfort and irritation.
- Have to be removed at completion of therapy - inconvenience
What is a pilocarpine ocular insert (ocusert)? What is the reservoir? What is the white annual border made of to make it easier for patient to visualize?
- Membrane-controlled reservoir system
- Pilocarpine is sandwiched in between two ethylene-vinyl acetate membranes
- Alginic acid matrix serves as a reservoir for pilocarpine
- White annular border made of ethylene-vinyl acetate copolymer with titanium dioxide (pigment) that makes it easier for the patient to visualize
What are the examples of intraoccular implants?
Summary of Ocular Delivery Systems
