Eye preparations are sterile preparations directly used for the treatment of the eyes. It can be divided into ophthalmic liquid preparations (eye drops, eye washes, intraocular injection solutions, etc.), ophthalmic semi collagen body preparations (eye creams, eye creams, eye gel, etc.), and ophthalmic solid preparations (eye films, eye pills, intraocular inserts, etc.). Ophthalmic liquid preparations can also be packaged in solid form, with additional solvents prepared to prepare a solution or suspension before use.

Due to the sensitivity and structural specificity of the eyes, although ophthalmic preparations are topical preparations, their safety and quality controllability have always been of concern to people. At present, the quality requirements for ophthalmic preparations in various countries are basically equivalent to those for injections.

Eye drops are sterile preparations, and due to the limitations of packaging materials, non terminal sterilization production processes are generally used. Single dose eye drops are generally produced using an integrated blowing, filling, and sealing process. The process research of eye drops should refer to relevant sterilization/aseptic process guidelines to determine the key steps and parameters of the production process. Compatibility studies of components such as pipelines, filter cartridges, and seals that come into direct contact with the drug solution should be conducted according to the production process. Attention should also be paid to the production process. Detailed process validation data should be provided in the materials, including aseptic validation data (sterilization filtration system validation, aseptic process simulation test validation, packaging system sealing validation, sterilization method and sterilization validation data for internal packaging materials that come into direct contact with drugs, and retention time validation). In addition, the control of the production environment should be explained to prove the effectiveness. The production process of drugs meets the requirements of aseptic production, confirming the safety and quality controllability of drugs.

The dosage of eye drops should be consistent with the reference formulation, and the types and amounts of excipients in the prescription should usually be consistent with the reference formulation (95%~105%). pH regulators and osmotic pressure regulators may be different from the reference formulation, but the reasons should be labeled and explained to prove that it does not affect the quality, safety, and effectiveness of the product (in this case, corresponding non clinical or clinical trials need to be conducted).

Eye drops used for corneal trauma treatment or surgery must be absolutely sterile and packaged in single doses. Antibacterial agents must not be added to such eye drops. Multi dose eye drops should generally be supplemented with appropriate antibacterial agents, and the antibacterial efficacy of the prescription should comply with the provisions of the Chinese Pharmacopoeia Antibacterial Efficacy Test Method, ensuring that it can guarantee the quality requirements of the entire product life and use period.

The quality attributes of eye drops include the following: characteristics, identification, solution clarity and color, osmotic pressure molar concentration H、 Visible foreign objects, insoluble particles, loading/unloading amount, related substances, enantiomers, antibacterial agent content, antibacterial efficacy, viscosity, relative density, buffer capacity, content, sterility, drip volume, water loss rate, residual ethylene oxide during sterilization process, packaging compatibility, and elemental impurities.

PH: To ensure the stability of the drug and reduce irritation, the pH value of eye drops should generally be controlled within the range of 6.0-8.0. A pH below 5.0 or above 9.0 can cause significant irritation, increase tear secretion, and lead to rapid loss of drugs, which can damage the cornea.

Osmotic pressure: The range of osmotic pressure that the eyeball can adapt to is equivalent to a sodium chloride solution with a concentration of 0.6% to 1.5%, slightly higher than that of an injection solution. The normal range of osmotic pressure and molar concentration of human blood is 285~3100m0smo1/kg. Due to the dilution and buffering effects of tears, it is best to adjust the osmotic pressure of eye drops to isotonic or hypotonic. The osmotic pressure molar concentration ratio of general eye drops is controlled between 0.9 and 1.1.

Viscosity: Increasing the viscosity of eye drops can prolong the contact time between the medication and the conjunctiva or cornea, thereby affecting the efficacy and safety of the drug, and reducing irritation to the eyes. The suitable viscosity range for eye drops is between 4.0 and 5.0 cPa.s.

Buffer capacity: Quantitatively represents the buffering capacity of a buffer solution, that is, the amount of substance required to add a strong acid or a strong base per unit volume of buffer solution when the pH changes by 1 (unit: mo1/L).

Visible foreign matter: The requirement for visible foreign matter in eye drops is slightly lower than that in injection solutions. Generally, eye drops stored in glass containers are inspected for visible foreign objects in the ejected liquid using the inspection method; The eye drops packaged in plastic containers should be visually clear under 30001x illumination, without any metal shavings, glass shavings, large fibers, or other insoluble foreign objects. Visible foreign objects are the inspection items with the highest defect rate found in daily inspections, and they are also the difficulty in quality control of ophthalmic preparations. The most common reason is that sterilization does not cause visible mold spots, bacterial colonies, or turbidity during the storage and transportation of the drug solution. There are also factors such as unreasonable prescriptions that lead to the gradual precipitation of sediment during product placement.

Insoluble particles: According to the microscopic counting method specified in Section 0903 of the 2020 edition of the Chinese Pharmacopoeia, the limit is wider than that of injections and can be formulated based on reference preparations.

Antibacterial agents: Most eye drops are packaged in multiple doses and are subject to environmental, storage, and operator factors during use, posing a risk of microbial contamination. Research has shown that the rate of bottle mouth contamination during the use of eye drops is relatively high, while the rate of bottle interior contamination is low. The main microorganisms infecting the bottle mouth are Gram positive cocci, and the main microorganisms contaminating the bottle interior are fungi. Therefore, it is necessary to add appropriate and effective antibacterial agents to prevent microbial contamination during use. However, long-term use of eye drops containing preservatives can also cause some degree of damage to the ocular surface. Meanwhile, the antibacterial efficacy of eye drops is directly related to the content of antibacterial agents, and a decrease in the content of antibacterial agents may lead to a decrease in antibacterial efficacy, thereby increasing the possibility of microbial contamination. The Chinese Pharmacopoeia 2020 edition, Part Four, stipulates that "antibacterial agents with low safety risks should be selected as much as possible, and product labels should indicate the type and quantity of antibacterial agents".

Drip volume: The local therapeutic effect of eye drops is mainly achieved through corneal absorption, entering the aqueous humor and exerting therapeutic effects; The normal capacity of the human conjunctival sac is only 1041, and the volume of a drop of eye drops is generally 4041. Most of the medication is washed away by tears or absorbed through the nasal mucosa into the whole body, causing adverse reactions. Therefore, the clinical use of eye drops should follow the usage requirements in the instructions, and the drip volume should be consistent with the reference preparation. The drop volume of the reference preparation is an important reference for us to choose eye drops bottles.