Pharmaceuticals: Ophthalmic Ointments Quiz

Ocular Drug Delivery

• Ocular drug delivery is a critical area of modern eye care, with significant opportunities and challenges.
• The front of the eye is accessible, allowing for simple topical treatments (eye drops).
• The back of the eye requires more advanced treatment methods, including intraocular injections and implants to allow sustained drug release (up to 2 years).
• Emerging therapies target cells, genes, and proteins, in addition to small molecules.

Classification of Ocular Drug Delivery Systems

• Liquid: Solutions, suspensions, and sol-to-gel systems (Powders for reconstitution)
• Semisolid: Ointments and gels
• Solid: Ocular inserts

Ideal Ophthalmic Delivery System Requirements

• Prolong contact time with corneal tissue
• Simple and comfortable administration for the patient
• Non-irritating formulation
• Appropriate rheological properties
• Good corneal penetration

Common Ophthalmic Dosage Forms

• Solutions, suspensions, ointments
• These forms are rapidly drained from the eye due to tear flow and lacrimal drainage.

Anatomy and Physiology of the Eye

• Diagram of the eye with labeled parts (Sclera, Iris, Cornea, Pupil, Lens, Conjunctiva, Vitreous, Choroid, Optic Nerve, Macula, Retina).

Ocular Drug Delivery Routes and Elimination Pathways

• Route 1: Cornea - The primary route for topically administered drugs entering the aqueous humor.
• Route 2: Blood Retinal Barrier - Limits systemic drug entry into the posterior segment of the eye.
• Route 3: Intravitreal Delivery - Direct access to the back of the eye.
• Elimination 1: Aqueous humor - Drains into the systemic circulation via uveoscleral pathways.
• Elimination 2: Trabecular Meshwork and Schlemm's Canal - Outflow route for aqueous humor.
• Elimination 3: Vitreous Humor - Drug elimination via diffusion into the anterior chamber.
• Elimination 4: Blood Retinal Barrier - Drug elimination via diffusion across the blood retinal barrier.

Common Ocular Conditions and Interventions.

• Dry Eye Syndrome: Tear volume insufficiency or poor tear quality leads to ocular surface disease. Management includes control of symptoms and protection of the ocular surface with tear substitutes and mucolytic drops. Severe cases may require anti-inflammatory drops and surgical interventions to reduce punctal drainage.
• Cataracts: Cloudiness of the lens often related to age. Surgical replacement of the lens (with a synthetic intraocular lens) is the standard treatment.
• Glaucoma: Optic nerve damage resulting in visual field loss; characterized by elevated intraocular pressure (IOP). Medical interventions and surgical procedures can reduce IOP to halt progression.
• Age-Related Macular Degeneration (AMD): A degenerative disorder affecting the macula, leading to loss of central vision.
• **Endophthalmitis:**Inflammation of the internal eye layers frequently resulting from procedures such as surgery and trauma.

Topical Ophthalmic Preparations

• Basal tears: A continuous secretion with an average rate of 1.2 µL/minute and reflects stimulus (irritants) with variability up to 400 µL/minute
• Blinking: Moves tear fluids & foreign materials, to the nasal corner of the eyelid.
• Tears contain lysozymes and immunoglobulins that help fight infections.
• Eye drops are cleared rapidly (4-23 minutes).

Formulating Ophthalmic Preparations

• Osmolality: Healthy eyes have an average osmolality of 302 mmol/kg. Dry eyes often show higher tear film hyperosmolality, which contributes to disease symptoms. Hypotonic solutions increase corneal permeability and induce edema; hypertonic solutions dehydrate corneal epithelium and are irritating.
• pH: Tear pH is near neutral (6.9-7.5), regulated by substances like carbon dioxide, bicarbonate, and proteins. Diluting solutions administered into the eye through reflex tears, is a common response. Recovery to original pH typically takes a few minutes to 20 minutes.
• Buffering: Solutions are adjusted and buffered to ensure proper comfort (in range of physiological pH), stability, and bioavailability to enhance preservative efficacy, and aqueous drug solubility.

Topical, Semisolid Ophthalmic Preparations

• Ointments: Ophthalmic ointments provide extended residence time, enhancing drug absorption, and are used for drugs with poor aqueous solubility.
• Gels: More favorable than ointments for water-soluble drugs. Different polymers like PVA, poloxamers, HPMC, and carbopols are used.
• Mucoadhesive Systems: Increase contact time via special polymers that bind to mucin in the ocular surface.

Intraocular Implants

• Non-biodegradable: Reservoir-type (coated with semi-permeable polymers) or monolithic (homogeneous mix of drug and polymer) devices. Drug delivery is constant. Usually necessitates surgery for placement/removal.
• Biodegradable: Metabolized by the body, eliminating the need for surgery (e.g., Ozurdex). Suitable for sustained drug release.
• Examples: Vitrasert and Ozurdex as specific biodegradable systems

Sterility of Ophthalmic Preparations

• Sterility of ophthalmic preparations is essential as infections can cause major vision loss.
• Terminal sterilization, filtration or preservatives control/minimize contamination.

Surface Tension

• Healthy tear fluid surface tension ranges from 43.6 to 46.6 mN/m
• Solutions with lower surface tension can potentially disrupt the tear film.
• Surfactants can help solubilize or disperse drugs.

Viscosity

• Viscosity-enhancing polymers are used to prolong drug retention in the precorneal tear film.
• Increased tear film thickness due to the viscosity enhancing polymers can help stabilize the aqueous layer.

Topical Liquid Ophthalmic Preparations

• Solutions: Fast-acting; easily administered. Must be isotonic and homogenously formulated.
• Suspensions: Designed to increase dwell time within the eye. Particle size and shape are carefully selected due to irritation potential.

Submicron Emulsions and Prodrugs

• Submicron emulsions: Enhance the absorption of poorly water-soluble drugs to improve contact time and drug release.
• Prodrugs: Enhance corneal penetration by improving drug's lipophilicity or by changing drug's structure.

Ocular Inserts

• Insoluble inserts are multi-layered structures containing drugs and polymer membranes.
• Release rate of the drug within the body is controlled by various factors (polymer composition and membrane thickness).

Additional Considerations

• Barriers to Ocular Drug Absorption: Tears, surface area of the cornea, and cornea anatomy are key barriers.
• Specific Preparations: Ointments, gels, submicron emulsions, and drugs are important for ocular use.
• Critical Factors: pH, osmolality, viscosity, and preservative use are vital to consider in preparation development.