From the heat transfer and mass transfer, the mechanism of vacuum freeze-drying was studied, and the corresponding mathematical model was established. It was helpful to find the influencing factors of the process and predict the distribution of time, temperature and vapor pressure. The current research is mainly limited to homogenous liquid phase, and some mathematical models have been proposed, such as uniform ice retreat model, sublimation model, adsorption-sublimation model, and so on. Although these models describe the process of vacuum freeze-drying to varying degrees, there are still many limitations in practical applications. Process optimization control is based on the above mathematical model. The control scheme is divided into a quasi-steady-state model and an unsteady model.
Strictly control the production process
As the freeze-drying process of biological products and pharmaceuticals is more complicated, in order to ensure the quality and energy saving of freeze-dried products, it is necessary to strictly control the pre-freezing temperature, sublimation and heat absorption in the production process, so that the various stages of the freeze-drying process in accordance with the pre-defined process route jobs.
Application Tip I: Maintain a reasonable pre-freezing temperature
In the vacuum freeze-drying process, it is necessary to first pre-freeze the dried medicine, and then in the vacuum state, the water is directly changed from ice to air to dry the medicine. Throughout the sublimation phase, drugs must remain frozen, otherwise products with good properties cannot be obtained. In the pre-freeze phase, the pre-freezing temperature must be strictly controlled (usually a few degrees below the eutectic point of the drug). If the pre-freezing temperature is not low enough, the drug may not be completely frozen, and it will swell and foam when vacuum sublimation. If the pre-freezing temperature is too low, it will not only increase the unnecessary energy consumption, but also reduce the biological drug. The survival rate after lyophilization.
Application Tip Two: Focus on Sublimation and Heat Absorption
In the dry sublimation stage, the material needs to absorb heat (per gram of ice completely sublimated into water vapor absorbing about 2.8 kilojoules of heat). If the medicine is not heated or the calories are insufficient, when the water sublimates, it absorbs the heat of the medicine itself to lower the temperature of the medicine, resulting in a decrease in the vapor pressure of the medicine, thus causing a decrease in the speed of sublimation and prolonging the entire drying time. Productivity decline; if the drug is heated too much, the rate of sublimation of the drug will increase, but after counteracting the heat absorbed by the sublimation of the drug, the excess heat will increase the temperature of the frozen drug itself, causing the drug to partially or even melt completely. Cause dry shrinkage and blistering of the drug, the whole drying will fail.
Application Tip 3: Use Computer Automation to Control
In order to obtain a good freeze-dried drug, a lyophilization curve should be formulated based on the performance of each freeze-dryer and the characteristics of the drug in the freeze-drying process, and then the machine should be controlled so that the freeze-drying process can be carried out. The change in temperature corresponds to a pre-established freeze-drying curve. At present, vacuum freeze-drying process control can be controlled by a computer to control the production system to work according to a preset freeze-drying curve. For example, the computer can control the lyophilization process of streptomycin sulfate in two stages. In the first stage, the water is sublimated from the frozen material at a temperature lower than the melting point, and about 98% to 99% of the water is evaporated. Both are removed at this time. In the second stage, the temperature of the material is gradually raised to or slightly higher than room temperature, and the water content can be reduced to less than 0.5% at this stage. The pre-freezing temperature in this process is about -40°C and the time is about two hours. In the dry sublimation phase of lyophilized drugs, the temperature of the material is approximately -30°C to -35°C, and the absolute pressure is approximately 4 to 7 Pascals. The final drying temperature of streptomycin can be raised to 40°C and the total drying time is about 18 hours. The use of computerized automated control systems helps to ensure that medicines meet quality requirements.