- Preparation of the solution
- Filling and sterilization
• The aqueous eye drop vehicle containing any necessary preservative, antioxidant, stabilizer, tonicity modifier, viscosity modifier or buffer should be prepared first. Then the active ingredient is added and the vehicle made up to volume.
Characteristics, Properties and Requirements of Eye Drop Preparations
Eye solution has to be free from foreign particles and clear, obtained by filtration.
Therefore, filtration equipment is very important and well washed, so free from foreign material. Work on eye preparations should also be in a clean environment.
Use of Laminar Air Flow and must not be spilled and leak, will give unity to the preparation of clear solution free of foreign particles. In some problems, clarity and sterility done in the same filtration step. Containers and lids must be clean, sterile and does not shed. Containers and lids are not carrying particles in solution during prolonged contact during storage. Sterility test is normally done.
Stability of drug in solution depends on the chemical properties of ingredients, product pH, storage methods (especially the temperature), other additive and type of packaging
Drugs such as pilocarpine and fisostigmin active and fit on the eye at pH 6.8 however, the pH of the chemical stability (or stability) can be measured within a few days or months. With this drug, the material loses chemical stability of less than 1 year. Conversely pH 5, both drugs stable in recent years.
If the oxygen sensitivity is a factor, to improve stability adequate antioxidant is desirable. Plastic packaging, low density polyethylene "Droptainer" provide patient comfort, can increase deksimental for stability with the release of oxygen produces oxidative decomposition of medicinal materials.
Buffer and pH
Ideally, eye preparations preferably at a pH that is equivalent to the eye fluid is 7.4. In practice, this is rarely achieved. majority of the active ingredient in ophthalmology are the salt of a weak base and the most stable at acidic pH. This can generally be made in nsoluble corticosteroid suspension, usually most stable at acidic pH.
Buffer systems were selected in order to have adequate capacities to obtain a pH range of stability for the duration of life of the product. Buffer capacity is the key.
Tonicity means that the osmotic pressure given by the salts in aqueous solution, the solution is isotonic with the eyes of others when magnefudosifat colligative solution is the same solution. isotonic eye solution to be considered when solution tonicity equal to 0.9% Na Cl.
Actually, the eye is more tolerant of variations in tonicity. Then, it can usually tolerate the same solution for the range 0.5% -1.8% NaCl. Provide choice, isotonicity always desirable and is particularly important in intraocular solution. However, this is not required when the total stability of the products considered.
USP allows the use of viscosity chelating material to extend the contact time in the eye and for absorption of the drug and its activities. Materials such as methylcellulose, polyvinyl alcohol and hydroxy methyl cellulose is added periodically to increase the viscosity.
Researchers have studied the effect of increased viscosity in the contact time in the eye. 25-50 cps viscosity generally increased significantly improved long-range contacts in the eye.
The use of additives in solution allowed, however, the selection of a certain amount. Antioxidants, especially sodium bisulfate or metabisulfat, used with concentrations up to 0.3%, especially in saline solution containing epinephrine. Other antioxidants such as ascorbic acid or acetylcysteine are also used. Antioxidant effect as a stabilizer to minimize oxidation of epinephrine.
The use of surfactants in the preparation of the eye is restricted. Nonionic surfactants, such small toxic class of compounds used in low concentrations, especially the suspension and is associated with the clarity of the solution.
Nonionic surfactants, in particular can react with the adsorption with antimicrobial preservatives and inactive components of the preservative system.
Cationic surfactants are used gradually in the eye solution but almost invariable as an antimicrobial preservative. benzalkonium chloride in the range 0.01 to 0.02% with concentrations of toxicity limiting factor. Benzalkonium chloride as a preservative is used in large quantities in commercial eye solution and suspension.
• The BP has stringent requirements for the absence of particulate matter in eye drop solutions. Sintered glass filters or membrane filters of 0.45 – 1.2 micron pore sizes are suitable. The clarified solution is either filled directly into the final containers which are sealed prior to heat sterilization or filled into a suitable container prior to filtration sterilization. Clarified vehicle is used to prepare eye drop suspensions which are filled into final containers and sealed prior to sterilization.
This can take the form of:
- Autoclaving at 115°C for 30 minutes or 121°C for 15 minutes
- Heating at 98 - 100°C for 30 minutes together with either benzalkonium chloride 0.01% w/v or chlorhexidine acetate 0.01% w/v or phenylmercuric acetate or nitrate 0.002% w/v or thiomersal 0.01% w/v. This method is described in the BP (1980) but is no longer a pharmacopoeial recommended method.
- Filtration through a membrane filter having a 0.22micron pore size into sterile containers using strict aseptic technique. Filling should take place under Grade A laminar airflow conditions. A suitable filter holder for extemporaneous preparation is illustrated in Figure 4. The filter assembly is sterilized by autoclaving before use.
- Dry heat sterilization at 160°C for 2 hours is employed for non-aqueous preparations such as liquid paraffin eye drops. Silicone rubber teats must be used.
Immediately following sterilization the eye drop containers must be converted with readily breakable seal, such as a viskring, to distinguish between opened and unopened containers.
General Labelling requirements for eye drop containers