Biopharmaceutical Considerations In Topical Ocular Drug Delivery

Abstract

1. Despite the accessibility of the front of the eye, efficient delivery of drug to treat various ocular disorders is a challenge to the formulation scientist. The majority of ophthalmic medications are formulated as eye drops. Due to anatomical constraints, the volume that can be administered is limited to approximately 30 microL. This, together with the efficient clearance system that exists in the front of the eye, makes it difficult to maintain an effective pre-ocular drug concentration for a desired length of time. Various formulation strategies have been used to increase pre-ocular retention of eye drops. The most successful of these has been the inclusion of viscosity enhancing polymers, particularly those able to interact with the mucous layer on the eye surface or those that can undergo a transition from a solution to a gel under the conditions of the pre-ocular area. 2. When the target site is intra-ocular, drug must be absorbed from the pre-ocular region into the eye. The main route for absorption is across the cornea. However, absorption of drug across the cornea is inefficient due to its impermeable nature and small surface area. Thus, the intra-ocular bioavailability of topically administered medications is typically less than 10%. 3. Corneal permeability favours moderately lipophilic compounds. These compounds often have a low aqueous solubility. Problems in ocular drug delivery and formulation are compounded for poorly soluble drugs that must be formulated as suspensions. 4. Reformulation of ophthalmic suspensions as solutions has many advantages. This may be achieved by complexation using cyclodextrins. Solubilization using cyclodextrins can overcome many of the formulation problems. However, it is unclear as to their potential for improving ocular bioavailability, which is seemingly drug dependent and may be influenced by both the physicochemical properties of the drug and the complex formed.

Preparation of arginine–glycine–aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization

“…8 Because of these issues, suspension eyedrops are quickly cleared: 90% of the drug is cleared within 2 minutes, and only 5% of the administered dose permeates into the cornea. 9 Nanotechnology has found a place in the medical field by providing new and more efficient ways to deliver treatment. Nanoparticles (NPs), especially biodegradable ones, have also found applications in ophthalmology, by providing safer, less invasive, cheaper treatment options, and by effectively increasing drug concentration in the eyes.…”

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

“…This is due in part to the unique structure of the eye, various application routes, and formulation types that are used for ocular drug delivery. Since it is difficult to collect ocular pharmacokinetic data and data modeling may be difficult, the literature is very limited about ocular pharmacokinetics and mostly covers the measurement of drug levels in aqueous humor following ocular administration (Macha and Mitra 2003;Schoenwald 1990;Mishima 1981;Davies 2000). It is difficult to develop quantitative predictions for interspecies dose adjustments since most of these studies were performed in rabbit eyes with different anatomical and physiological features (such as blinking rate, tear volume, and corneal dimensions) relative to human eyes and because there is little or no data available in human eyes.…”

Soft Glucocorticoids: Eye-Targeted Chemical Delivery Systems (CDSs) and Retrometabolic Drug Design: A Review

“…Because of this a significant portion of the applied drug is absorbed through nasolacrimal duct and the mucosal membranes of the nasal, oropharyngeal, and gastrointestinal tract to pass to the system. It has been found that no more than 2% of medication introduced topically to the eye is adsorbed [35][36][37]. Again clinical studies by various workers reveal that the main biological barrier for penetration to the eye is represented by the cornea.…”