Unit 6 Freeze-drying

冷冻干燥 Freeze-drying Freeze-drying works by freezing the material and then reducing the surrounding pressure and adding enough heat to allow the frozen water in the material to sublime directly from the solid phase to the gas phase. 冻干 lyophilization lyophilizer 冷冻干燥 crydesiccation

Advantages Ease of processing a liquid, which simplifies aseptic handling Enhanced stability of a dry powder Removal of water without excessive heating of the product Enhanced product stability in a dry state Rapid and easy dissolution of reconstituted product

Disadvantages Increased handling and processing time Need for sterile diluent upon reconstitution Cost and complexity of equipment

冷冻干燥机 Freeze-dryer

六大组成部件 控制系统控制系统 干燥箱 捕水器捕水器 真空系统真空系统 制冷系统 加热系统

干燥箱（冻干箱） Freeze-drying Chamber

冷凝器（捕水器）

制冷系统（压缩机）

真空系统 （真空泵）

加热系统

药用冻干机 Medicinal Freeze-dryer 液压系统 在位清洗系统（ CIP ） 在位灭菌系统（ SIP ）

药用冻干机类型 实验型 中试型 生产用 间歇式 连续式

Three stages Freezing First, the product is frozen at a sufficiently low temperature to reach a vitreous state where pure water has crystallized and the amorphous content remains in the interstitial region.

Primary drying In the second stage, the product undergoes sublimation at a temperature below the glass transition or collapse temperatures and crystallized water is sublimed. Secondary drying Finally, secondary drying is undertaken at a higher temperature to remove sorbed water from the interstitial region.

药品冻干工艺

The lyophilization process Step 1 Dissolving the drug and excipients in a suitable solvent, generally water for injection (WFI). Step 2 Sterilizing the bulk solution by passing it through a 0.22 micron bacteria-retentive filter.

Step 3 Filling into individual sterile containers and partially stoppering the containers under aseptic conditions. Step 4 Transporting the partially stoppered containers to the lyophilizer and loading into the chamber under aseptic conditions. Step 5 Freezing the solution by placing the partially stoppered containers on cooled shelves in a freeze-drying chamber or pre-freezing in another chamber.

Step 6 Applying a vacuum to the chamber and heating the shelves in order to evaporate the water from the frozen state. Step 7 Complete stoppering of the vials usually by hydraulic or screw rod stoppering mechanisms installed in the lyophilizers.