Problems With Freeze Drying And Their Corresponding Solutions

A lot of problems may appear in a product’s freeze-drying process. And this usually has nothing to do with the lyophilization machine you use, but the way how you use it. The flawed product is a reflection of such problems. Good freeze-dried products should have a good physical form, such as full appearance, smooth surface, non-shrinkage, etc. However, problems with freeze drying will result in bad target products. The causes and solutions of these problems with freeze drying are now analyzed and discussed.Problems With Freeze Drying

Problems with freeze drying — freeze-dried products have shrinkage and bubbling

Such problems with freeze drying are usually because the sublimation stage is heated too fast, or the sublimation stage has not ended and the analysis stage is entered in advance. Excessive temperature leads to local melting, and the melting part evaporates from liquid to gas, resulting in volume reduction. Or the dry product dissolves into the liquid, causing the volume to shrink. Severe melting will produce bubbling.

The solutions to problems with freeze drying like this are to reduce the temperature of the sublimation stage, extend the time of the stage, increase the vacuum of the freeze-drying chamber, and control the product temperature to be more than 5℃ below the eutectic point or disintegration point temperature.

Problems with freeze drying — the product is melted out of the bottle

The temperature in the pre-freezing process is too high, the time is too short, the product is not completely frozen, and the pre-freezing is not complete. Or the temperature in the sublimation stage is too high, and some products are melted out of the bottle during vacuum sublimation and drying.

Problems with freeze drying at this circumstance are usually solved by reducing the pre-freezing temperature and extending the pre-freezing time so that the product is completely frozen and then sublimated by vacuum.

Problems with freeze drying —shrinkage, voids, and debris appear soon after the product is out of the chamber.

The product is not completely dried, and there are residual ice crystals.

This can be solved by extending the sublimation drying time or increasing the analytical drying sublimation temperature.

Problems with freeze drying — the product presents uneven color and layering phenomenon.

One situation is that the lower part of the freeze-dried mass is delicate and the upper part is frizzy and has crystalline patterns. This is caused by the slow freezing rate. In the process of slow pre-freezing, the bottom first forms ice, and the solute is concentrated upward. Another situation of such problems with freeze drying is that the concentration of a substance in the solution is too high. After the solution is left for a long time, the substance precipitates due to changes in temperature or pH.

The problem in the first situation can be solved by accelerating the pre-freezing speed or using repeated freezing method. And the one in the second possible situation can be solved by reducing the concentration and adjusting the prescription to stabilize the solution pH or reducing the resting time of the solution.

Problems with freeze drying — a hard shell appears on the surface of the product

Hawach's lyophilization machine

Air-impermeable glass-like structure is formed on the surface of the product during pre-freezing. The product heats up after sublimation begins, and some products melt and shrink. The shrinkage of the product causes the surface layer to crack, so the sublimation of the lower layer can proceed normally.

The solution is to do heat treatment during pre-freezing.

Problems with freeze drying —the bottle is broken and loses its bottom during freeze-drying

1. Poor bottle quality;
2. An excessive amount of solution;
3. The pre-freezing speed is too fast.

This sort of breakage problems with freeze drying has corresponding solutions:
1. Manufacturers with good quality and a good reputation should be selected. Generally speaking, high borosilicate silicone bottles are not easy to break;
2. Control the amount of solution;
3. In the pre-freezing stage, the temperature should be slowly cooled or there is a holding time near the eutectic point to reduce the temperature difference between shelf and product.