A Review: Ocular Drug Delivery System

Developing a drug delivery system that specifically targets a particular tissue of the eye remains a significant challenge for researchers. The eye is generally divided into two main segments: anterior and posterior. The structural differences within each ocular tissue layer act as major barriers to drug absorption, regardless of the route of administration—topical, systemic, or periocular. In this study, our focus is on the various absorption barriers associated with all three delivery routes. The eye is resistant to foreign substances because of its distinct anatomy, physiology, and biochemistry, thereby posing an ongoing challenge for pharmaceutical scientists to overcome its protective barriers without inducing permanent tissue damage. In order to bypass ocular drug delivery barriers and enhance ocular bioavailability, several traditional and advanced drug delivery systems have been formulated, including emulsions, ointments, suspensions, aqueous gels, nanomicelles, nanoparticles, liposomes, dendrimers, implants, contact lenses, nanosuspensions, microneedles, and in situ thermosensitive gels for the previously mentioned ocular disorders. Traditional ophthalmic formulations such as solutions, suspensions, and ointments are no longer adequate to effectively treat these conditions. Moreover, such drugs typically fail to reach deeper ocular tissues like the retina, vitreous, or choroid, making alternative routes of administration more suitable as new technologies continue to emerge. From a drug delivery perspective, the eye remains highly challenging to study, as its anatomy, physiology, and biochemistry make it resistant to external substances. It provided a detailed overview of ocular drug delivery, covering aspects such as the eye’s anatomical structures, various ocular diseases, barriers to drug delivery, different administration routes, classification of dosage forms, a range of nanostructured platforms, methods of characterization, strategies to enhance ocular delivery, and emerging future technologies.

Conventional Ophthalmic Formulations:

Conventional ophthalmic formulations refer to the traditional dosage forms used for delivering drugs to the eye. These mainly include:

Eye drops/solutions –

The most common form, but limited by rapid precorneal elimination and low bioavailability. Topical liquid or solution-based eye drops are the most common, safe, noninvasive, and patient- friendly method of ocular drug delivery, providing rapid therapeutic action. After instillation, they produce a burst of drug permeation, followed by a rapid decline in concentration, typically following near first-order kinetics. To enhance drug retention, penetration, and overall ocular bioavailability, various excipients can be incorporated into eye drop formulations, such as viscosity enhancers, permeation enhancers, and cyclodextrins. Viscosity enhancers help extend precorneal residence time and improve bioavailability by increasing the formulation’s thickness; common examples include hydroxy methyl cellulose, hydroxy ethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, and polyalcohols. On the other hand, permeation enhancers facilitate corneal absorption by temporarily altering corneal integrity.

Suspensions –

Useful for poorly water-soluble drugs, providing longer contact time than solutions. Suspensions represent another type of noninvasive ocular topical drug delivery system. They are defined as dispersions of finely divided, insoluble active pharmaceutical ingredients (API) in an aqueous medium containing appropriate suspending and dispersing agents. Essentially, the solvent system serves as a saturated solution of the API. The suspended drug particles remain in the precorneal area, which helps extend drug contact time and prolong the duration of action compared to drug solutions. The length of drug activity in suspensions is influenced by the particle size.

Ointments –

Increase drug retention due to their viscosity, but may cause blurred vision and discomfort.

Ophthalmic ointments are another category of carriers designed for topical drug delivery. These formulations consist of a blend of semisolid and solid hydrocarbons (such as paraffin) with melting points close to the physiological temperature of the eye (around 34 °C). The selection of hydrocarbons is based on their biocompatibility. Ointments enhance ocular bioavailability and provide sustained drug release.

Emulsion –

Emulsion-based formulations provide a useful strategy to enhance both the solubility and bioavailability of drugs. Two primary types of emulsions are employed as carriers for active pharmaceutical ingredients: oil-in-water (o/w) and water-in-oil (w/o) systems. For ophthalmic applications, o/w emulsions are more commonly used and are preferred over w/o emulsions because they cause less irritation and offer better ocular tolerance. Examples of marketed ocular emulsions in the United States include Restasis™, Refresh Endura® (a non-medicated emulsion for eye lubrication), and AzaSite®. Research has shown that emulsions can extend precorneal retention, improve corneal drug permeation, enable sustained drug release, and consequently enhance ocular bioavailability.