Water Content of Hygroscopic Lyophilized drugs

This application describes a method to measure the actual water content of the lyophilized drugs in the closed vial. Gas phase extraction principle is used throughout the whole measuring procedure, so that the sample is never exposed to air.

Background:

Lyophilisation, also known as freeze-drying, is a dehydration process typically used to preserve a material. Lyophilisation works by freezing the material and then reducing the surrounding pressure to allow the frozen solvent to sublime directly from the solid phase to the gas phase. After this drying process, the final residual water content in the product is very low e.g. in the order of 0.1% to 4%.

Pharmaceutical companies often produce lyophilized drugs to increase the shelf life of the products, such as live virus vaccines, biologics and other injectables. By removing the water from the material and sealing the material in a glass vial, the material can be easily stored, shipped, and later reconstituted to its original form for injection.

Due to the drying process, lyophilized drugs are usually very hygroscopic. This means that they are taking up atmospheric humidity as soon as the vial is opened.Herein, we describe a method to measure the actual water content of the lyophilisate in the closed vial. Throughout the whole measuring procedure, the sample is never exposed to air.

The absolute water content is determined by a Karl Fischer autosampler and the unknown sample weight is provided through an automated balance method based on the principle of backweighing. In order to fulfill USP 921 regulation and to prevent the sample from oxidation, nitrogen is used as inert carrier gas.

Furthermore, a scanning function is performed to select a suitable oven temperature for the sample.

Download the application for stepwise procedure for automated water content determination of hygroscopic lyophilisates.