Yingtai: Methods for Determining The End Point of Analysis Drying

Yingtai: Methods for Determining the End Point of Analysis Drying

(I) Temperature Approach Method: Product temperature is often used as an indicator to determine the end of drying, and it is an indirect measurement method. The temperature method utilizes the thermal equilibrium between the dried product temperature and the shelf temperature to measure it. As the water vapor sublimates, the product temperature will gradually rise. When the product temperature is consistent with the shelf temperature, it indicates that the residual moisture in the product has essentially evaporated.

(II) Vacuum Degree Method: The vacuum degree method uses the correlation between the rate of pressure increase and the amount of residual moisture to determine the end point of freeze-drying. It is generally believed that when the pressure inside the freeze-drying chamber is low and reaches a stable state, it is considered that the material has completed drying. However, it usually takes a considerable amount of time for the pressure inside the freeze-drying chamber to reach a stable state. It is generally believed that if the leak rate of the freeze-drying chamber is small and constant, the relative change rate of pressure increase can indicate the end point of drying. This is a method currently used more frequently to determine the end point of drying.

(III) Weighing Method: The weighing method uses the relationship between the product's weight loss rate and its moisture content to measure it. During the drying process, continuously or periodically weigh the weight loss in the freeze-drying chamber or the amount of ice frozen on the condenser until the weight loss rate tends to balance, which can determine whether the drying is complete. For large freeze-dryers, the weighing method produces a relatively large error, while for small freeze-dryers, this method is more convenient and accurate, so this method is only suitable for laboratory freeze-dryers.

(IV) Humidity Method: The principle of the aluminum oxide film humidity-sensitive element for measuring humidity is that the porous aluminum oxide film easily absorbs water vapor from the air, thereby changing its own dielectric constant. Therefore, the capacitance value of the capacitor made up of aluminum oxide as the electrolyte will change with the partial pressure of water vapor in the air. So, by measuring the capacitance value, the relative humidity of the air can be obtained. At the end point of drying, the partial pressure measured by the electronic water vapor sensor will suddenly drop. Therefore, when the conventional product temperature response method cannot provide accurate information, this method can be used. In addition, residual gas analyzers have been used as detection tools for pharmaceutical freeze-drying. A residual gas analyzer is a small quadrupole mass spectrometer, and this system generally includes a quadrupole mass analyzer, a diffusion pump, one or more mechanical pumps, and a series of sampling valves. The biggest disadvantage of the residual gas analyzer is its high price and large equipment size.

(V) Pulse Nuclear Magnetic Resonance (NMR): The NMR method is an analytical means that is relatively easy to measure water content. By studying the relaxation time of protons, it can characterize the activity of protons and provide information related to the binding force and mobility of water molecules. Basic principle: Pulse nuclear magnetic resonance technology can quantify the number of liquid protons in the sample below 0°C. Below 0°C, the free water in the sample is frozen, contributing to the solid part of the nuclear magnetic resonance signal, while bound water is often not frozen between -25~-15°C. Nuclear magnetic resonance spectroscopy can directly observe and perform structural analysis in the solid state without destroying the sample.