Formulation Considerations for the Management of Dry Eye Disease

Abstract

Dry eye disease (DED) is one of the most common ocular surface disorders characterised by a deficiency in quality and/or quantity of the tear fluid. Due to its multifactorial nature involving several inter-related underlying pathologies, it can rapidly accelerate to become a chronic refractory condition. Therefore, several therapeutic interventions are often simultaneously recommended to manage DED efficiently. Typically, artificial tear supplements are the first line of treatment, followed by topical application of medicated eyedrops. However, the bioavailability of topical eyedrops is generally low as the well-developed protective mechanisms of the eye ensure their rapid clearance from the precorneal space, thus limiting ocular penetration of the incorporated drug. Moreover, excipients commonly used in eyedrops can potentially exhibit ocular toxicity and further exacerbate the signs and symptoms of DED. Therefore, formulation development of topical eyedrops is rather challenging. This review highlights the challenges typically faced in eyedrop development, in particular, those intended for the management of DED. Firstly, various artificial tear supplements currently on the market, their mechanisms of action, as well as their application, are discussed. Furthermore, formulation strategies generally used to enhance ocular drug delivery, their advantages and limitations, as well as their application in commercially available DED eyedrops are described.

Recent Advances in the Excipients Used for Modified Ocular Drug Delivery

“…This is because the drug is administered directly into the eye lobe, thus protecting the rest of the body from systemic exposure. Agarwal et al refer to this route as the only way to achieve therapeutic concentrations in the eye [ 19 ]. Moreover, topically applied drugs escape first-pass metabolism and thus reach higher concentrations in the target area [ 20 ].…”

“…The field of developing new ophthalmic formulations is highly challenging. Several new formulations are available but topical eye drop solutions and emulsions are still predominant because they are easy to prepare, act immediately, and are accepted by patients [ 19 , 38 ]. In addition to eye drops, there are other topical ophthalmic preparations such as emulsions [ 37 ], ointments, and gels [ 39 , 40 ].…”

Trends in Topical Prescriptional Therapy for Old Patients With Dry Eye Disease in Six Major Areas of China: 2013–2019

“…There are many classes of drug on the market for DED treatment including ocular lubricants, anti-inflammatory drops, essential fatty acids, and so on. Topical formulations offer several advantages such as simple, convenience and painless use (Agarwal et al, 2021). However, many treatments are poorly supported by evidence-based practices (Jones et al, 2017), and the efficacy of some (e.g., cyclosporine) is debated (Seitzman and Lietman, 2018).…”

Assessment of a Cationic Emulsion to Control the Tear Film Evaporation Rate

“…Artificial tears and lubricants are considered one of the most common methods to treat dry the signs and symptoms of DE. 5 Formulations containing electrolytes, mucomimetic agents, or oil emulsion are significantly helpful in DE management. 6 However, the main drawback of most of these formulations is their short retention time, as the solution can easily drain via the lacrimal drainage system.…”

“…Different oils such as castor oil, mineral oil, soya bean oil, and phospholipid liposomal have been used to develop oil-in-water emulsions to manage DE signs and symptoms. 5 , 9 …”