Why a bit of moisture in freeze-dried products can be a good thing

Rules are meant to be broke and “the drier, the better” is a perfect freeze-drying example of that. Of course, you perform the lyophilization process to remove water, but there are certain products that are sensitive to damage from overdrying. Read on to see which compounds you should be extra careful with when it comes to moisture content control. And discover how moisture mapping can help you stay within the ideal moisture range for your products.

My wife and I are pretty good bakers, but one of our biggest challenges has been chocolate chip cookies. We both love eating these treats, especially warm from the oven. Our only problem is that they typically tend to come out a bit overbaked, crunchy and dry.

I am glad to share with you that this will be the case no more. We had a visit from some Canadian friends and the husband baked us a few batches of chocolate chip cookies. He took them out of the oven when they were still looking pretty raw to me, but he insisted that they will continue to bake on the rack. And so they did. And they were some of the yummiest, moistest cookies we have ever had.

Lesson learned. A bit of moisture goes a long way in chocolate chip cookies. But you might be surprised that it goes a long way in freeze-drying too.

One of the applications of freeze-drying is to increase the shelf life of a product by removing water. It is easy to assume that the drier the product, the better. This principle holds true for molecules with a direct degradation pathway triggered by water. But this statement is not entirely correct when it comes to other types of compounds such as biopharmaceuticals.

There are certain products that require some level of moisture to maintain quality and functionality.

Biological products, such as cells, vaccines or proteins, typically require higher moisture content than chemicals at the end of the lyophilization process. Studies have shown that proteins need a small amount of water to help maintain higher-order structures, even in lyophilized state. Other types of products, such as certain types of blood plasma formulations also need a minimal amount of water to achieve efficient dry-heat viral inactivation. Another point to consider is that many products could suffer damage due to overdrying in the freeze dryer.

To address these issues, I would recommend carrying out stability studies to assess the ideal moisture content of a formulation. To achieve this, you should design a freeze-drying cycle that keeps all product vials within a certain moisture range, with both minimal and maximal specifications.

But how can you determine the amount of moisture present in your final products? Moisture analysis is typically performed using Karl Fischer titration or thermogravimetric analysis. These methods are nice, but they are also time consuming and they will destroy your sample.

Instead, I would suggest performing lyophilization chamber moisture mapping using head space analysis by frequency modulated spectroscopy.

This method offers quick and non-destructive analysis, so you can accurately measure the moisture content of your samples and the quality of entire batches. You can see an example of how the results look like below:

moisture mapping, freeze drying, lyophilization

The method is a nice way to ensure final moisture levels are kept within the ideal range for your application.

This is not the first time baking has inspired me to blog about lab matters. Well, cooking, especially baking, has a lot in common with chemistry, so this is probably no surprise. But see for yourself how a good pumpkin pie (how season-appropriate) brought me to thoughts on mobile phase and its influence on selectivity in chromatography. And go even farther back and read how I tied cheesecake preparations to the “golden mean” between cost and productivity in flash chromatography. I know this won’t be enough to satisfy your appetite for knowledge, so keep dropping by to get more food for thought here.

Till next time,

The Signature of Bart Denoulet at Bart's Blog