Shall we use shell freezing to speed up manifold freeze drying?

If you are looking for ways to perform manifold freeze drying faster, then you’ve landed in the right place. In this post, I briefly discuss the main factors that affect drying rates during lyophilization. Then I point out how shell freezing can bring you substantial time saving benefits compared to bulk freezing and offer a few examples to illustrate my point. Spend a few minutes here, to discover how you can shave many minutes off your own workflow.

 

We had a few warm sunny days already this year so I used the opportunity to move the drying rack from the laundry room to the garden. I love the smell of sun-kissed laundry. My brother and his wife were over for lunch, but I excused myself and started to fold the freshly washed bed sheets so that they would fit onto the rack. As I started to hang them, my brother couldn’t help but comment that the bed sheets would need a million years to dry as they are folded in so many layers. Well, he was wrong. They dried in three days!

Of course he had a point and if I had the luxury of space, I would spread the bed sheets into one large thin layer. I would certainly save some drying time.

The same concept is universally applicable. Take the freeze drying process.

Generally, the greater the surface area relative to the volume, the faster the product dries. A larger surface results in more water molecules leaving the matrix.

But let me go into a few more details here. In a freeze-drying process, sublimation occurs at the surface of the sample. Drying begins at the top of the product and a layer forms at the location where the drying is occurring. During the drying process, this well-defined sublimation front travels from top to bottom of the product. Drying is efficient at the beginning of the method, but the efficiency decreases as the sublimation moves downwards. The process becomes more challenging because the sublimated water molecules must pass through the dried product, also known as the “cake”, before they can leave the matrix.

The drying rate at which a certain product is freeze-dried depends on various factors, such as pressure and temperature. Features of the product itself, such as the product volume to be freeze-dried, as well as the type of product arrangement also affect the drying rate. As previously mentioned, the greater the surface area of the product relative to volume, the faster the drying rate.

Having said that, a good way to improve the drying efficiency of manifold freeze-drying is to use shell freezing.

In manifold applications, if liquids are to be dried in flasks in a layer thicker than 1 to 2 cm, it may be beneficial to use shell freezing.

During shell freezing, the product is frozen under rotation in a cooling bath. The rotation spreads the product on the wall of the flask and thin product layers are created. This could be performed with a rotavapor equipped with a Dewar accessory. For example, freezing 200 ml of water in a 1 L flask would result in a bulk of 4.5 cm high. By rotating the flask during the freezing process, the frozen product is spread on the inner wall of the flask to produce an even, homogeneous layer that is less than 1 cm thick (see below).

shell freezing, shell frozen flask

Experimental data (see graph below) shows that under similar manifold freeze-drying conditions, the sublimation rate is more than doubled when the sample is frozen using shell freezing (23.9 gwater/flask/h; orange squares) than when frozen in bulk (9.9 gwater/flask/h; blue dots).

sublimation, sublimation speed, shell freeze drying

To sum things up, the drying rate generally depends on the surface area relative to the volume of product. The larger the surface area, the faster the product dries, since more water molecules can leave the matrix. In order to increase product surface area when using manifold freeze drying, you should certainly consider using shell freezing. With this approach, the product is spread on the inner wall of the flask while freezing, which helps to increase the sublimation rate compared to bulk freezing.

Funnily, previous drying woes have also made me think about chromatography. See how the limitations of my dryer made me think about how ELSD helps overcome limitations in chromatography in one of my previous blog posts.

How are you finding the balance between freeze drying and chromatography topics on the blog so far? I love spicing things up and being more inclusive. I’m already excited about the next blog post, and you should be too. I won’t keep you waiting long!

 

Till next time,

The Signature of Bart Denoulet at Bart's Blog
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