The Challenge: Dry Eye and the Limits of Artificial Tears

Dry eye disease is characterized by inflammation, loss of tear film integrity, and reduced tear volume. The condition results from a disruption in the balance between the lipid and aqueous components that make up the protective tear film. Left unmanaged, this imbalance leads to ocular surface damage, discomfort, and progressive visual impairment.

Artificial tear products, including widely used commercial brands, have been developed to alleviate symptoms by replenishing lubrication on the ocular surface. However, these formulations are delivered as eye drops, which are subject to rapid clearance from the ocular surface due to tear turnover and blinking. This limits their residence time and requires frequent reapplication to maintain symptomatic relief.

The underlying limitation is structural: conventional eye drops do not replicate the layered composition of the natural tear film, which consists of a mucus layer, an aqueous layer, and a lipid layer working together to protect and hydrate the ocular surface. A delivery approach that can generate a more durable, biomimetic tear film directly on the eye represents a meaningful step forward in dry eye management.

A Dissolvable Wafer Approach to Biomimetic Tear Film Replenishment

Integral BioSystems developed a dissolvable wafer ocular insert based on its proprietary NanoM Wafer ocular insert technology. Unlike sustained release applications of the NanoM™ platform, this variant is designed to dissolve within a predetermined time after placement, forming a surface-spreading aqueous-lipid interface that creates a long-lasting biomimetic tear film on the ocular surface.

Key design and functional attributes of the dissolvable NanoM™ Wafer include:

• Dimensions that fit comfortably under the lower eyelid without clinical intervention for placement
• A translucent hydrogel matrix upon hydration, permeable to oxygen, carbon dioxide, and water
• Greater than 90% water content in the hydrated state
• Biodegradable composition fabricated from combinations of aqueous polymers and lipids
• Dissolution time that can be modulated by adjusting the wafer composition, from rapid-dissolving to longer-lasting formats

The wafer is placed into the lower conjunctival fornix in dry form and hydrates in situ. Upon dissolution, the formulation spreads across the ocular surface, generating a robust air-water interface with low surface energy designed to mimic the natural tear film structure.

Research Design and Methods

The research, presented at the 2025 ARVO Annual Meeting (Poster 4342 – A0498), characterized the dissolvable wafer technology across several parameters: surface energy of pre-film solutions, dissolution time, wafer thickness, flexural modulus, sterilizability, and in vivo tolerability in New Zealand White Rabbits.

Surface tension of pre-prototype solutions was measured using a Nanoscience Surface Tensiometer. Dissolution time was tested ex vivo on 8 mm, 200-micron wafers using distilled water at 37°C, and also measured in vivo. Flexural modulus was assessed by manual fold testing. Safety and tolerability were evaluated using the SPOTS ocular scoring system (Eaton et al. 2017), with tissue assessment conducted after wafer dissolution. Sterilizability was tested by exposing foil-packaged wafer prototypes to sterilizing radiation, followed by evaluation for visual degradation and dissolution time changes.

Key Findings from the Research

The following results are relevant for teams evaluating ophthalmic formulation development strategies for dry eye and tear film replenishment:

Surface energy and spreading behavior:

Multiple dissolvable wafer prototypes achieved surface tension values between 31.5 and 37.7 Nm/m, substantially lower than water (67.8 Nm/m) and commercial artificial tears such as Systane (58.1 Nm/m) and Systane Plus (40.0 Nm/m). Lower surface energy translates to a lower contact angle on hydrophilic tissue surfaces, enabling the dissolved formulation to spread more effectively across the ocular surface after dissolution.

Tunable dissolution time:

Dissolution time varied by composition, with some prototypes dissolving in under 30 minutes in vivo and others demonstrating ex vivo dissolution times of 4 to 5 hours. This tunability allows the platform to be configured for different clinical use cases, from rapid symptomatic relief to extended tear film replenishment.

Mechanical properties and tissue adhesion:

All prototypes demonstrated high flexural modulus with no stress fractures observed upon manual folding. The wafers adhered to the underlying tissue upon placement, and dissolution time could be extended through in situ interlocking with tissue. These properties support practical handling during self-administration and durable ocular surface contact during use.

In vivo safety and tolerability:

In a New Zealand White Rabbit model, single-use dissolvable wafers demonstrated no adverse effects at dissolution. SPOTS scoring across all evaluated parameters, including lid swelling, discharge, conjunctival hyperemia, iris hyperemia, pupillary light reflex, corneal opacity, and corneal vascularization, returned scores of zero across all animals (n=4 eyes). No abnormalities were observed.

Terminal sterilization feasibility:

Foil-packaged wafer prototypes exposed to sterilizing radiation showed no visual discoloration. Some decrease in dissolution time was noted post-sterilization, but the wafers remained functionally intact. This supports the feasibility of terminal sterilization for commercial-scale manufacturing.

What This Means for Ophthalmic Development Teams

For R&D and product development teams working on dry eye management or ocular surface devices, this research highlights several practical considerations:

• A dissolvable wafer format can generate a biomimetic tear film with lower surface energy than leading commercial artificial tears, supporting more effective and durable ocular surface coverage.
• Dissolution time is tunable by composition, allowing a single platform to serve both rapid-dissolving and extended-duration product configurations.
• The wafer demonstrated zero adverse effects in preclinical in vivo testing, with clean SPOTS scores across all ocular safety parameters.
• Terminal sterilization is feasible without compromising wafer integrity, an important consideration for regulatory pathway and manufacturing scalability.
• The platform can function as an ophthalmic medical device (no drug) to replenish tear film components, or it can be adapted for drug-loaded sustained release applications.

Integral BioSystems’ expertise in ophthalmic delivery and the NanoM™ platform positions the company to support drug development services and device development programs from early feasibility through process engineering and scale-up.

Read the Full Research

This blog post summarizes key findings from the ARVO 2025 poster by Ward, Guerrero, Bhardwaj, Belen, and Barman (Poster 4342 – A0498). To review the complete research, including detailed materials and methods, surface tension data, dissolution profiles, tolerability scores, and sterilization results, download the full poster (PDF).

Explore all Integral BioSystems research on the publications page.

Discuss Your Ophthalmic Development Program

Whether you are exploring dissolvable insert formats for dry eye management, evaluating the NanoM™ platform for a tear film replenishment product, or considering drug-loaded variants for ocular surface therapy, Integral BioSystems can support your program from feasibility through process engineering. Request a formulation consult to discuss your project and delivery objectives.