The moisture of products, the performance of lyophilizer, the control time of analytical drying and the temperature of analytical drying are the main factors affecting moisture. For freeze-dried products, the water content is required to be ≤ 3%. The high water content of freeze-dried products will decompose and shrink the products. The main reasons for the high water content of products are:
1. Too much liquid medicine. The thickness of liquid medicine filling volume is generally 10-15mm, which should not exceed 15mm. If the filling volume is large, it can be considered to replace containers with larger specifications to reduce the thickness of liquid medicine. Too thick liquid medicine will make the heat transfer effect worse in the drying process, which is not conducive to removing the water in the product, and the water in the product is too high.
2. The dried products absorb moisture again. For varieties that are easy to absorb moisture, if they are not handled properly after drying, the products will absorb moisture again, increasing the water content in the products. If the gas enters the freeze-drying box during venting, it is necessary to sterilize, filter and dry the gas entering the freeze-drying machine; The temperature of the product when it is out of the box will also affect the water content of the product. Therefore, the temperature of the product when it is out of the box is higher than that of the clean room to prevent moisture in the air from condensing on the product. In addition, the relative humidity of the clean room should be strictly controlled below 50%.
The appearance of products and the appearance of freeze-dried products are closely related to the freeze-drying curve performed!
The specific manifestations of poor appearance of freeze-dried products are shrinkage, crystallization, insufficient flocculent, etc. In the inspection process, the products with poor external appearance are removed and destroyed as waste products, which will greatly reduce the qualified rate of finished products and increase the production cost. Factors affecting the appearance of products include:
1. Effect of high or low solution concentration on the surface of traditional Chinese medicine solution in the process of preparation and drying. When the solution concentration is too high:
It is dried to form a dense surface. The surface layer has small pores and poor air permeability, and the water in it is difficult to pass through the surface layer, so it rises along the bottle wall, resulting in the product leaving the wall and shrinking; In addition, when the concentration is too high, the liquid medicine is easy to agglomerate during freeze-drying, and the appearance of the product is uneven. When the concentration is too low: the mechanical strength is low, and the product structure is relatively loose or even becomes powder after packaging and transportation, which affects the appearance of the product.
2. The product thickness is too thick. Generally, it should be 10-15mm. If the product is too thick, it is similar to the case when the concentration is too high, not only the drying time is longer, but also collapse and caking.
3. The temperature rise and fall is fast, and it is easy to cause the products to leave the wall and slow. Pre freezing speed: the product with a temperature drop of 10-15 ℃ per minute is called quick freezing, and the product with a temperature drop of 1 ℃ per hour per minute during the freeze-drying process of freeze dryer is called slow freezing. Generally, one-stage sublimation drying: the product temperature shall be reduced and the cooling rate shall be controlled at 5-6 ℃.
Below the eutectic point, the temperature rise shall be slow, preferably 5 ℃ per hour, and more than 90% of the water shall be removed at the end of phase I sublimation drying. Second stage sublimation drying: this stage is mainly to remove crystal water and solid adsorbed water. The heating rate can be accelerated, preferably 5-10 ℃ / h, but Zui final product temperature cannot exceed the safe temperature of the product, otherwise the activity of the product will be reduced, caking and poor solubility.
4. Bleeding speed. Before coming out of the cabinet, the bleeding speed should not be too fast, otherwise the vacuum degree in the box will suddenly change greatly, and a turbulent flow will be formed to rush into the container, making the products become flocculent or powder, affecting the appearance.
