Ophthalmic preparations refer to sterile dosage forms administered directly to the eye to exert therapeutic effects. The pharmaceutical excipients incorporated into eye drops primarily function to adjust the physicochemical properties of liquid formulations, preserve sterility and the chemical stability of active drugs, optimize ocular administration comfort, and enhance the bioavailability of medicinal ingredients. Commonly used pharmaceutical excipients are mainly categorized into the following types:

1. pH Adjusters and Buffer Systems

The human eye can tolerate a pH range of 5.0 to 9.0, while the optimal pH value for eye drops is generally maintained between 6.0 and 8.0. pH adjusters including boric acid, borax, sodium hydroxide and hydrochloric acid, together with buffer solutions such as borate buffer and phosphate buffer, are incorporated into formulations. These ingredients steadily sustain the solubility and chemical stability of active pharmaceutical ingredients, and effectively alleviate ocular irritation triggered by inappropriate pH levels upon eye administration.

2. Isotonicity Regulators

The osmotic pressure of human tears is equivalent to that of 0.9% sodium chloride aqueous solution. Excessively high osmotic pressure of eye drops will cause water loss in ocular surface tissues and lead to dry eye discomfort; hypotonic formulations, on the contrary, result in cell swelling of outer eye tissues and bring about stinging irritation. Common isotonicity regulators comprise sodium chloride, glucose, potassium chloride, glycerin and more. In industrial production, eye drops are routinely formulated to an isotonic state equivalent to 0.8%–1.2% sodium chloride solution to fit ocular physiological conditions perfectly.

3. Viscosity Enhancers & Suspending Agents

Viscosity Enhancers

A series of hydrophilic colloids are widely adopted, such as Methylcellulose (MC), Hypromellose (HPMC), Carbomer and Polyvinyl Alcohol (PVA). Proper viscosity reduction of surface tension prolongs the residence duration of drugs within the conjunctival sac, extends therapeutic efficacy and mitigates local eye irritation.

Suspending Agents

For suspension-type eye drops containing water-insoluble active ingredients, the above viscosity-enhancing colloids simultaneously act as suspending agents. They slow down the sedimentation rate of solid microparticles and avoid particle aggregation and caking throughout the shelf life of preparations.

4. Antimicrobial Preservatives

Multi-dose packaged eye drops are susceptible to microbial contamination from tears and ambient air once opened for repeated use. Adding antimicrobial preservatives is an indispensable measure to preserve sterility and prolong the expiry date of liquid formulations. Typical preservatives used in ophthalmic preparations include benzalkonium chloride, chlorobutanol, phenethyl alcohol, phenylmercuric nitrate and parabens. By contrast, single-dose eye drops for surgical application or wound care are normally preservative-free to prevent unnecessary ocular irritationEyeWiki.

5. Antioxidants and Metal Ion Chelating Agents

Oxidation-prone active drugs tend to undergo discoloration and chemical degradation under the influence of atmospheric oxygen, light irradiation or trace metal ions. Formulations are supplemented with antioxidants (sodium sulfite, sodium metabisulfite, vitamin E, etc.) and metal chelating agents represented by disodium edetate (EDTA disodium). Such combination inhibits oxidative deterioration of medicinal components and guarantees long-term physicochemical stability of eye drops.

6. Solubilizers

Solubilizers encapsulate poorly soluble drugs inside micelle structures to remarkably elevate aqueous solubility of active ingredients, securing formulation stability and accurate dosage delivery. As the ocular surface is extremely sensitive to irritation, anionic solubilizers are barely applied in eye drop formulas. Only low-toxicity or non-toxic nonionic solubilizers are preferred for ophthalmic use, mainly categorized as below:

• Polysorbates: Polysorbate 80 (Tween 80) is the most prevalent option, extensively utilized to solubilize various poorly soluble ophthalmic medicines.
• Polyoxyethylene Castor Oil series: Polyoxyethylene Castor Oil 3 / 10 can efficiently solubilize specific active components; in certain formulas, it also generates synergistic effects with terpenoids to further improve formulation stability.
• Poloxamers: High-molecular nonionic surfactants exemplified by Poloxamer 188. Featuring ultra-low ocular irritation and toxicity, they serve dual purposes of solubilization and promoting ocular drug absorption.

7. Solvents

Water for Injection serves as the primary solvent for all eye drops. To balance solubilization of lipophilic drugs and physiological ocular tolerance, small amounts of polyhydric alcohols or polyethylene glycol are added as co-solvents:

• Glycerin: Acts both as a co-solvent to boost drug solubility and a humectant & isotonic regulator; nevertheless, high concentrations will cause obvious sticky sensation in eyes.
• Polyethylene Glycol (PEG): PEG 300 and PEG 400 are commonly used to solubilize fat-soluble active ingredients with mild ocular stimulation.
• Propylene Glycol: Possesses powerful solubilizing capacity, yet its dosage must be strictly controlled, as high concentrations will cause evident damage to corneal epithelial cells.