What is the benefit to microparticles in ocular products?
Encapsulate the drug and provide sustained release for prolonged times at target site
What is the benefit of chitosan for ocular preparations?
- Is a polycation, so binds to mucin (polyanion) via ionic interaction between primary amino groups (chitosan) and sialic and sulphonic acid substructures of glycosylated chains of mucins
- Hydroxyl and amino groups of chitosan may interact w/ mucin via H bonds
What does successful drug tx of various eye diseases depend on?
- Intrinsic activity of drug
- Ability of drug to cross biological barriers
- Maintenance of drug in lachrymal fluid for an extended period of time
Why is the eye difficult to study?
Isolated, highly protected organ
What are the 3 primary modes of drug delivery to the eye?
- Topical application to surface
- Administration to eye for absorption into eye
- Direct injection into eye (only done by trained professionals)
Are eye products for systemic absorption common? What do they depend on?
- No
- Depends on lachrymal drainage and subsequent systemic absorption
What are the objectives of ocular drug delivery?
- Retain drug formulations on the site of action for an extended period of time
- Achieve maximal local therapeutic outcomes while minimizing systemic effects
- Reduce drug irritability or any other adverse effects to their minimal levels
What are the physiological barriers of the eye?
- Tear turnover
- Naso-lachrymal drainage
- Blinking
What are the anatomical barriers of the eye?
- Static barriers which limit drug entry to anterior chamber (corneal epithelium, stroma, and blood-aqueous barrier)
- Dynamic barriers which are involved w/ drug clearance (conjunctival blood and lymph flow, tear drainage)
What is mucin? What is its function?
- Gel-like structure
- Protective role into the eye
- Permeation barrier which restricts ocular drug absorption
Why is only a small portion of topically instilled eye preparations absorbed?
- Precorneal loss
- Physiological and anatomical constraints
- Also solution drainage, lacrimation, tear turnover, tear dilution, and conjunctival absorption
- Low permeability of corneal epithelial membrane
What must be achieved for ocular permeability?
Balance of lipophilicity and hydrophilicity
What is the volume of precorneal fluid?
7-10 uL
What are the factors that influence drainage rate?
- Instilled volume (higher volume = faster drainage)
- Viscosity (increasing extends residence time in conjunctival sac)
- pH (instillation of acidic or alkaline solution results in tear secretion and loss of drug, so adjusted to 7-7.7)
- Tonicity (should be isotonic
Which drugs affect tear production and what is the effect?
- Epinephrine induces tear production
- Local anesthetics (ex: tetracaine) suppress it
What percent of tear fluid is protein? What is the effect of drug binding to tear proteins?
- 0.7% protein
- Drug binding results in reduction of total free rug available for action at target site
What are the layers of the cornea?
- Epithelial layer (lipophilic drugs penetrate through transcellular diffusion; paracellular diffusion limited to MW less than 100)
- Bowman’s layer
- Stroma (hydrophilic, so hydrophilic molecules traverse easily and lipophilic molecules have difficulty)
- Descemet’s membrane
- Endothelial layer (innermost; relatively porous allowing hydrophilic and lipophilic molecules through)
Where does melanin binding occur in the eye? Which drugs have high binding capacity for melanin? How does this affect release rate?
- Iris and ciliary body
- Ephedrine and timolol
- Only a small portion of bound drug is released at a very slow rate
Where are enzymes found in the eye?
Ocular tissues (cornea, lens, iris-ciliary body, retina)
Most of the dose forms for the eye are useful for _____
Delivering drug to anterior portion of eye which includes cornea, anterior chamber, iris, and lens
What makes it difficult to treat ocular tissues through systemic administration?
Blood-eye barrier (BEB), similar to BBB
What happens to drug that isn’t lost to lacrimal drainage?
Permeates mucous membranes of conjunctiva and is lost to systemic absorption before it can enter inner ocular tissues
Usually ____ of the applied dose is available to the posterior portion of the eye for absorption
Less than 5%
How can absorption occur across the cornea?
Transcellular and paracellular pathways
