Ocular and Ophthalmic Drug Delivery (3/25/26) - Pharmaceutics II

What structures of the eye are included in the Anterior Portion?

Iris

Pupil

Aqueous Humor

Cornea

Conjunctiva

Lens

Ciliary Body

What structures of the eye are included in the Posterior / Back Portion?

Sclera

Choroid

Retinal Pigment Epithelium (RPE)

Neural Retina

Fovea

Macula

Optic Nerve

Vitreous Humor

How is the structure of the eye divided?

How much of the eye is occupied by each segment?

Divided into two main parts

- Anterior Segment (1/3 of eye)

- Posterior Segment (2/3 of eye)

What is the most important parts of the eye included in the Anterior Segment to remember?

Posterior Segment?

Anterior Segment:

- 1. Tear Film

- 2. Corneal Barrier

- 3. Conjunctival Barrier

Posterior Segment:

- 4. Choroids

- 5. Blood-Retinal Barrier

- 6. Vitreous Humor

What type of ocular diseases affect the Anterior Segment of the eye?

Ocular Infections

- Keratitis, inflammation of Cornea

Ocular Inflammations

- Allergic Conjunctivitis via Pollen

Dry Eye Syndrome

- Eyes do not make enough tears to stay wet

Glaucoma

- Group of eye diseases that can cause vision loss and blindness by damaging the Optic Nerve

Cataract

- Develops when aging or injury changes the tissue that makes up the Lens of the eyes; presents as a cloudy area in the Lens

What type of ocular diseases affect the Posterior Segment of the eye?

Age-Related Macular Degeneration (AMD)

- Happens when aging causes damages to the Macula (part of eye that controls sharp, straight-ahead vision)

Diabetic Retinopathy

- Complication of Diabetes that affects the eyes; caused by damage to BVs in the Retinal Tissue

Macular Edema

- Makes the Macula swell, causing blurry vision; can be caused by many different conditions

What are the six main Ocular Routes of administration?

1. Intravitreal

2. Topical

3. Intravitreal Implant

4. Transscleral (Subconjunctival)

5. Systemic

6. Transscleral (Para Bulbar)

What is the Intravitreal route of administration for Ocular Delivery?

Ocular injection into the Vitreous Humor

What is the Topical route of administration for Ocular Delivery?

Non-Invasive route of drug administration to the front of the eye like eye drops

What is the Intravitreal Implant route of administration for Ocular Delivery?

Drug delivery by surgically implanting in the vitreous of the eye

What is the Transscleral (Subconjunctival) route of administration for Ocular Delivery?

Delivery beneath the Conjunctiva, circumventing the Cornea, and the drug passes through the Sclera to enter the Vitreous Humor (ex. AVASTIN)

What is the Systemic route of administration for Ocular Delivery?

Oral / Parenteral (aka IV) delivery....

What is the Transscleral (Para Bulbar) route of administration for Ocular Delivery?

Drug delivery involving above or below the eye globe

- Ex. delivery of anesthesia in case of cataract surgery

What route of administration for ocular delivery is used to deliver medication directly into the vitreous humor?

Intravitreal (Implant)

What are the limitations of the Intraocular Implant route of administration for Ocular drug delivery?

Increased risk of retinal detachment and intravitreal hemorrhage

Invasive (used of needle to poke, owwie)

What are the limitations of the Intravitreal Injections route of administration for Ocular drug delivery?

Increased risk of retinal detachment, hemorrhage, endophthalmitis, and Cataracts

Rapidly diluted

Repeat procedures are often necessary

What are the limitations of the Systemic Administration route of administration for Ocular drug delivery?

Limited / Variable Penetration

Potential for systemic toxicity

What are the limitations of the Topical Application route of administration for Ocular drug delivery?

Limited Penetration (<5%)

Rapid tear washout

Poor patient compliance

What are the three unique ways that drugs can be lost when utilizing Ocular drug delivery?

1. Immediate Loss due to Spillage

- Normal volume of tears ~7 microliters

2. Lacrimal Drainage

- Rate of tear production ~2 microliters per minute

3. Drug Absorption into the Conjunctiva

What are Ophthalmic Solutions (Eye Drops)?

Give an example.

Ocular dosage form that is:

- Sterile

- Free from foreign particles

- Prepared especially for instillation into the eye

Example: 0.9% NaCl as a vehicle to administer medication in the eye

What are Ophthalmic Suspensions?

Sterile liquid preparations that contain solid particles in a vehicle suitable for instillation into the eye

What are Ophthalmic Ointments and Gels?

Sterile semi-solid preparations containing ointment base intended for application to the CONJUNCTIVA or EYELID MARGIN

What are Ocular Inserts / Implants?

Give examples.

Ocular dosage forms that cannot be compounded, but instead must be manufactured; can be Biodegradable or Non-Biodegradable in nature

Vitrasert and Retisert (non-biodegradable implants)

What is Vitrasert?

Non-biodegradable ocular implant that consists of a 4.5mg pellet of Ganciclovir

Surgically implanted into the Vitreous and allows for Local and Sustained Release delivery for 5-8 months

Used in treatment of Cytomegalovirus (CMV) Retinitis

What is Retisert?

Non-biodegradable ocular steroid implant used for the treatment of Uveitis

What is a Biodegradable Implant used for?

Give an example.

24/7 drug delivery for several months

Example:

- Bimatoprost Ocular Implant approved by FDA for reduction of IOP in patients with Open-Angle Glaucoma (OAG) or Ocular Hypertension

Which type of treatment would elicit the best response from the Conjunctiva, Cornea, Anterior Chamber, and Iris?

Topical

Which type of formulation is NOT applicable to ocular administration?

Why?

Liniment

Intended to be used with rubbing / friction and contain irritant ingredients

Describe each of these physicochemical considerations for ocular administration:

- Tonicity

- Viscosity Enhancers

- Buffers

- Sterility

- Preservatives

Tonicity - lacrimal fluid is isotonic

Viscosity Enhancers - allow to remain in eye longer for drug absorption

Buffers - optimum pH is 7.2 +/- 0.2

Sterility - ABSOLUTE REQUIREMENT; special consideration for Pseudomonas aeruginosa

Preservatives - generally packaged in multi-dose containers, so preservatives are important (preservative-free usually in single-dose)

What are some examples of Preservatives used in Ocular Dosage Forms?

Benzalkonium Chloride

Benzethonium Chloride

Thimerosal

What are some examples of Viscosity Enhancers in Ocular Dosage Forms?

Hydroxypropyl Methylcellulose (HPMC)

Polyvinyl Alcohol (PVA)

What are the five main types of excipients in Ocular Dosage Forms?

What are their main functions?

1. SOLUBILITY ENHANCERS - makes the hydrophobic drugs of ocular dosage forms more soluble and bioavailable in Ocular tissue

2. VISCOSITY ENHANCING AGENTS - helps overcome the short residence time of most ocular forms and their subsequent low penetration into layers of the eye

3. BUFFERING AGENTS - maintains acid-base balance of solution / formulation to reproduce natural system of the tear film

4. PENETRATION ENHANCERS - act as barriers due to presence of tight junctions and multicellular architecture; limits drug permeability after topical instillation on eye surface

- Primary Mechanism is to modify the stability of the tear film and mucus layer (incl. Membrane Fluidization) and temporarily opening tight junctions

5. PRESERVATIVES - prevents inadvertent bacterial contamination with repeated patient use

What is a common example of a Solubility Enhancer use in eye drop formulations?

Cyclodextrin (CD)

What are some common examples of Buffering Agents used in eye drop formulations?

Acetic, Boric, or Hydrochloric Acids

Sodium Carbonate or Borate

Citrate-Based Preparations

What are the three main categorizations of Penetration Enhancers?

1. Chelating Agents

2. Surfactants

3. Cyclodextrins

What excipient can be used to limit the presence of microorganisms in a liquid formulation?

Benzalkonium Chloride

What are five examples of Preservative-Free Formulations?

1. Dorzolamide / Timolol (Cosopt PF) - ophthalmic solution in single-use containers; indicated for GLAUCOMA

2. Latanoprost (Iyuzeh) - ophthalmic solution in single-use containers; indicated for GLAUCOMA

3. Lotemax Ointment - preservative-free ocular steroid; indicated for Post-Surgical or Inflammatory conditions

4. DEXTENZA - preservative-free SR formulation of dexamethasone encapsulated in Hydrogel; indicated for Pain and Inflammation after ophthalmic surgery

5. Preservative-Free Lubricating Eye Drops - Blink Tears Preservative Free Lubricating Eye Drops

What is an absolute requirement for Ocular Dosage Forms?

Sterility