Watering your knowledge on spray drying and freeze drying

Today I am very excited to introduce you to a newcomer to the blog: spray drying. I have mentioned spray drying before, but I would like to feature this method more frequently on the blog, as it is a frequently used technique in R&D formulation labs. But just to throw in an old face into the mix and make the introduction, I’ve decided to discuss both spray drying and freeze drying with you. In this post, you can formulate a better idea of how spray drying and freeze drying compare. Are you as excited as me? Dry on!

We were invited for a dinner with some close friends of ours over the weekend. After some glasses of wine, we started telling stories from the good old days. The main course included fish and potatoes, so my wife decided to share a funny story about the beginning of our relationship and our cooking habits back then. Apparently, I used to make fish sticks in the oven and she in the frying pan and vice versa for the fries.

It’s been many years since we made this kid-friendly dinner, but I think we would have stuck to our old habits were we to make fish sticks again. I think oven-made fish sticks are less oily and crispier, she defends her fried fish sticks as juicier and faster to make.

It wasn’t until I was lying in bed that I thought about all the different ways we have of achieving the same thing: cooked fish. We could boil, bake, fry, broil, even smoke the fish! And it is exactly the same in the laboratory. Many techniques could lead you to the same results. In fact, this is something I’ve already touched upon in a previous post about how rotary evaporation and freeze drying can be used to concentrate proteins.

But drying techniques include more than just laboratory evaporation and freeze drying. There is also another method, which I am very excited to introduce into the blog: spray drying.

I will admit that I have talked about spray drying before, particularly when I discussed spray drying and freeze drying methods in protein formulation. But everyone loves a good rivalry, so I think the best way to really submerge you in the spray drying topic is to give you a general comparison of the method versus an old-blog-favourite: lyophilization.

If you haven’t had a chance to read all of my freeze-drying posts, let me give you a quick introduction into this method.

Freeze drying

Freeze drying is based on the principle of sublimation, where solid materials are directly transformed to the gaseous phase. The process of freeze drying, also known as lyophilization, consists of three steps: freezing, primary drying and secondary drying. Since water molecules can induce mobilization of your solution, stability of your sample can be improved by water removal and embedding your proteins in a glassy matrix through lyophilization. Samples, such as freeze-dried proteins, can have greater storage stability than those in liquid solutions, but you must be careful not to alter the structure of your sample during the freezing and dehydration stresses stemming from lyophilization.

To develop successful formulations using a freeze-dryer, you should consider the following physical properties of your sample:

  • Glass transition temperature (Tg)
  • Residual moisture content

As well as operational parameters, such as:

  • pH
  • Cooling rate

You can also introduce stabilizers to protect your sample during the freezing step. These types of stabilizers are called cryoprotectants. Stabilizers used during the lyophilization step are called lyoprotectants and they function through water replacement and hydrogen bond formation. Excipients, on the other hand, have to potential to provide a glassy matrix to decrease unwanted interactions and reduce sample mobility in a solid dosage form.

So how about the spray drying part of spray drying and freeze drying?

Spray drying

Spray drying is a single-step process to provide powder particles with the required size and morphology. The process involves atomization, drying and separation of particles. Briefly, you feed your sample solution through an atomizer to create a spray, which is in turn expose to a heated gas stream to promote rapid evaporation. Once sufficient liquid mass has evaporated, the remaining solid material in the droplet forms particles, which are separated from the gas stream using a filter or a cyclone. Thanks to the short processing time, spray drying is considered as a mild technique for producing stable particle powders.

Particle formation time is a function of the initial liquid droplet size, droplet composition and evaporation rate. The rate of particle formation is a key parameter that dictates the required residence time, the scale of equipment and processing parameters needed to produce the required particle size at the desired production rate.

The Peclet number (Pe), which refers to the proportion of droplet evaporation rate and the diffusional motion of the solutes in the spray drying process, can govern the morphology and density of the final particles. These particles are either dense or hollow.

The following parameters are important for fine tuning your spray drying process to your needs:

  • Solute concentration
  • Feeding flow rate
  • Flow rate of hot air
  • Solubility of additives through effects on evaporation rate
  • Inlet temperature

Here a few considerations to bear in mind if you would like to use a spray dryer, nano spray dryer or encapsulator:

  • Large molecules with low diffusional coefficients, low solubility and high density experience fast surface saturation at high temperatures. Albumin and growth hormones are two examples of these types of molecules.
  • High surface-active agents, such as leucine and trileucine also saturate the surface rapidly; solutes cannot diffuse to the center of the droplets (Pe > 1) and generate hollow particles with low density
  • Thermo-sensitive samples may experience degradation during atomization due to loss of hydration layer in contact with hot air, as well as exposure to air/liquid interface at the droplet surface
  • Shear stress in the structure of your sample might also occur during the atomization step
  • Excipients used as stabilizers could provide a functional shield surrounding the sample to prevent exposure of the sample to the interfacial surface or hot atmosphere

Spray drying and freeze drying: when to choose which one?

I have complied the advantages, disadvantages and frequent applications of spray drying and freeze drying in the following table for you:

Freeze DryingSpray Drying
Benefits- Increases stability of products that are unstable in liquid state
- Simplifies storage of product
- Improves product shelf life
- Enables shipment between different climates and environments
- Gentler process with product temperatures below 0°C in primary drying and 20 - 30°C during secondary drying
- Vials can be sealed in-situ of the freeze dryer, thus avoiding potential contamination when the cycle is complete		- High-throughput and scalable drying technique due to continuous workflow, rather than batch-by-batch processing
- Simple and fast one-step process
- Lower initial investment for equipment
- Ability to dry at atmospheric pressures
Limitations- Requires large initial investment for equipment
- Not suitable for all active ingredients
- Not suitable for all processing and production volumes		- Higher product temperature above 80°C and shear stress with potential negative effects on efficacy, viability, taste, smell, colour, consistency, nutritional value, biological yield, sample degradation
Typical Applications- Preservation of different cell types, fine chemicals, laboratory reagents, injectable vaccines, food samples and dairy products
- Best suited for formulations that do not require further processing after drying as freeze drying is typically performed with product directly filled in vials or other containers
- Preferred method in the biopharmaceutical industry to preserve a wide range of pharmaceutical formulations and biologicals		- More suitable for bulk processing than vial-based drying
- Suitable for food, robust bulk pharmaceuticals, as well as complex products, such as microencapsulated bacteria, nano particulates in material science and chemistry

Warning, spoilers ahead! Similarly to how I conclude all types of posts where I attempt to compare techniques (I did just do column chromatography versus flash chromatography versus prep HPLC), I believe that both spray drying and freeze drying are excellent techniques, but which one is better for you depends on your application. You need to establish how high the quality of your final product should be, what downstream processes could occur, and the speed and cost-efficiency needs of your process before you pick one drying method.

If you would like a more in-depth look into spray drying and freeze drying, I have two free resources that are excellent at giving you essential theory and advice on how to optimize the processes. One is a comprehensive spray drying guide, whereas the other is an illustrated toolkit for freeze drying.

Now if you manage to read them all at once, keep dropping by the blog to see if I cover any topics that might be missing in there!

Till next time,

The Signature of Bart Denoulet at Bart's Blog