# Biomaterials for Ophthalmic Applications
## 2 Biomaterials in Ophthalmology
### Artificial Tears
#### 2.3.2. Formulation of Lacrimal Supplements and Tear Substitutes  
The term artificial tears mainly refers to products sold without medical prescription, whose purpose is to replace and/or supplement the natural tear film; however, they do not allow the underlying pathophysiology of DED to be addressed [75; 79]. Tear substitutes include a variety of products to target one or more layers of the tear film and have similar compositions. Artificial tears must have several short-term benefits, should not irritate the eye, should improve eye lubrication, decrease tear film evaporation, have a good retention time and should not change the eye optics. The ultimate goal is to prevent corneal damage and alleviate symptoms with few side effects. The aqueous base is the more abundant component. To improve its lubrication time and retention on the ocular surface, several viscosity improvers are usually incorporated [8; 79]. Each artificial tear varies in terms of composition, viscosity, duration of action, presence or absence of preservative, osmolarity and pH [80], although they generally have a pH of 6.5 to 7.5, close to the pH of human tears [75]. Conventional ophthalmic dosage forms such as eye drops (formulated as solutions or suspensions), gels and ointments are preferred for administering drugs to the ocular surface. Its relative ease of use, non-invasiveness, low cost of production and its ease of manufacture offer undeniable advantages. However, the ocular aqueous solutions experience a very short contact time with the ocular surface, due to rapid nasolacirimal drainage, resulting in low ocular bioavailability [81]. Ointments are formulated with a specific blend of mineral oil and petroleum. Some contain lanolin, which can irritate the eyes and delay wound healing in the cornea or contain parapons as preservatives. In general, ointments do not promote bacterial growth and therefore do not require preservatives but are not well tolerated by patients with severe dry eye [82]. Ointments can be used for prolonged action, especially during eye surgery or during night applications. The change in the refractive index between the tear film and ointment causes blurred vision, which is one of the main disadvantages [75; 83]. Gels containing cross-linked high-weight molecular acrylic-acid polymers, have longer retention times than artificial tear solutions, but have a lower visual staining effect than Vaseline ointments [82]. During its use, vision is initially blurred, but the phenomenon disappears quickly [75]. Viscosity-improving agents include carbomer 940, carboxymethyl cellulose (CMC), hyaluronic acid (HA), hydroxypropylmethylcellulose (HPMC) and polyvinylpyrrolidone (PVP), as well as mixtures thereof [75; 79; 80]. They can increase the time of permanence in the eye due to their mucoadhesive properties [74; 83]. HPMC and PVA are widely used in artificial tears, although they have a short duration of action [83]. Viscosity agents make it possible to increase the tear film thickness, improve tear retention to the surface and protection of the ocular surface, decrease drying and help maintain physiological corneal thickness [79]. Osmoprotectors are a group of solutes capable of maintaining normal cellular metabolism, even under extreme osmotic stress, decreasing cellular apoptosis and inflammatory cytokines and increasing the number of goblet cells. Trehalose is a natural disaccharide with the dualproperty of bioprotection and osmoprotection that prevents desiccation, apoptosis of eye cells, protects against ultraviolet-induced oxidative damage, accelerated corneal healing and restores osmotic balance as well [79]. Quercetin, epigallocatechin gallate, n-propyl gallate and gallic acid showed good bioavailability, were effective in scavenging free radicals and can be effective in protecting the corneal epithelium from oxidative damage [79]. Benzalkonium chloride (BAC) is the most used preservative in eye drops.