The stability of l-alanyl-l-tyrosine pharmaceutical preparations is affected by various factors, and its stability can be improved by optimizing the formulation design, improving the preparation process, controlling the storage conditions, and other methods. The details are as follows:
I. Formulation Design
Selection of Appropriate Solvents: The solubility and stability of l-alanyl-l-tyrosine vary in different solvents. When water is chosen as the solvent, its stability can be improved by adjusting the pH value to an appropriate range. Generally, a slightly neutral environment helps to reduce the hydrolysis and degradation of the drug. An appropriate amount of cosolvents, such as ethanol and propylene glycol, can also be added to improve the solubility of the drug. At the same time, it may reduce the interaction between drug molecules and water molecules, and decrease the occurrence of hydrolysis reactions.
Addition of Stabilizers: Antioxidants such as vitamin C, vitamin E, and sodium sulfite can prevent the drug from being oxidized in the air. Metal ion chelating agents such as ethylenediaminetetraacetic acid (EDTA) and its sodium salt can form stable complexes with metal ions in the solution, avoiding the catalytic oxidation reaction of the drug by metal ions. In addition, some surfactants, such as polysorbate-80 and poloxamer, can be added. They can form a protective film on the surface of drug particles, preventing the aggregation of drug particles and the transformation of crystal forms. At the same time, they can also reduce the contact between the drug and air, water, etc., and improve the stability.
II. Preparation Process
Freeze Drying: For the aqueous solution preparations of l-alanyl-l-tyrosine, freeze drying is a commonly used method to improve stability. By freezing the drug solution at a low temperature and then removing the water by sublimation under vacuum conditions, the degradation of the drug during the high-temperature drying process can be avoided. At the same time, the drug after freeze drying is in the form of a loose powder, which is conducive to long-term storage and maintaining its activity. During the freeze-drying process, parameters such as the freezing rate, drying temperature, and vacuum degree need to be optimized to obtain high-quality freeze-dried products.
Spray Drying: Spray drying is also an optional drying method, especially suitable for preparing micronized preparations of l-alanyl-l-tyrosine. The drug solution is sprayed into hot air, and the solvent evaporates rapidly to form tiny particles. During the spray drying process, parameters such as the inlet air temperature, outlet air temperature, and spraying rate should be controlled to avoid the degradation of the drug due to excessive heating time or too high a temperature. Compared with freeze drying, spray drying has the advantages of high production efficiency and low cost, but it may have a certain impact on the stability of the drug, and process optimization is required.
III. Storage Conditions
Temperature Control: l-alanyl-l-tyrosine pharmaceutical preparations should be stored at a low temperature, and the general recommended storage temperature is between 2 - 8°C. Low temperature can reduce the movement speed of drug molecules, slow down the chemical reaction rate, and reduce the degradation of the drug. Avoid exposing the preparation to a high-temperature environment, such as direct sunlight and near a heater, to prevent the drug from deteriorating due to heat.
Humidity Control: Humidity also has an important impact on the stability of l-alanyl-l-tyrosine. A high-humidity environment may cause the drug to absorb moisture, thus triggering reactions such as hydrolysis and oxidation. Therefore, the preparation should be stored in a dry environment. Desiccants such as silica gel and calcium chloride can be used to absorb the surrounding moisture and maintain the dryness of the storage environment. At the same time, the packaging material should have good moisture-proof performance, such as using aluminum foil bags, plastic bottles lined with desiccants, and other packaging methods to prevent external moisture from entering the packaging.
Light Protection: l-alanyl-l-tyrosine is sensitive to light, and light may trigger the photolysis reaction of the drug, leading to the destruction of the drug structure and a decrease in its activity. Therefore, the pharmaceutical preparation should use light-proof packaging materials, such as brown glass bottles and aluminum foil packaging, to reduce the influence of light on the drug. During the storage and transportation process, the preparation should also be avoided from being exposed to strong light.
