Granulation is a process widely used in modern industries such as pharmaceuticals, food, and chemicals. However, there are many types of granulation technologies. And each has its own advantages and disadvantages. Which method should you choose for your product? This article will provide you with some guidance.
What Is Granulation Technology?
Granulation is the process of aggregating fine powder particles to form larger granules. Through granulation, fine powders with poor flowability, prone to generating dust or prone to component separation, can be transformed into granules with better processing properties.
2 Main Types of Granulation Technologies
Based on whether a liquid binder is used, granulation techniques are generally divided into two main categories: dry granulation and wet granulation.
Dry Granulation
What Is Dry Granulation?
Dry granulation is a process in which powder is formed into granules through mechanical pressure without the addition of liquid binders. The main steps in dry granulation typically include compaction, milling, and screening.
What Materials Are Suitable for Dry Granulation?
Dry granulation is particularly suitable for moisture-sensitive and heat-sensitive materials. It is also ideal for processing active pharmaceutical ingredients (APIs) prone to degradation in wet conditions.
Types of Dry Granulation
- Roller Compaction: Roller compaction is the most widely used dry granulation technology in the pharmaceutical industry. Powder is fed through a feeding system between two counter-rotating rollers, where it is compressed into ribbons or flakes. These are then crushed and sieved to produce the desired granules. This process is a form of continuous manufacturing and is well-suited for large-scale industrial production.
- Slugging: Slugging is a traditional dry granulation process. The powder is first compressed into large slugs using a heavy-duty tablet press, and then ground and sieved. Currently, slugging is primarily used for laboratory development, small-scale production, and research into specialized formulations.
Advantages of Dry Granulation
Dry granulation does not require the use of liquids and is suitable for materials that are sensitive to moisture and heat. It also does not require a drying step, so it may help you reduce energy consumption. And it has a relatively simple process.
Drawbacks of Dry Granulation
Dry granulation is prone to generating fines, and the particle uniformity may be poor. The compaction process may cause the particles to become over-compacted. Sometimes, it may affect the subsequent tabletting performance.
Wet Granulation
What Is Wet Granulation?
In wet granulation, you add a liquid binder solution to a powder to make the particles agglomerate and grow. Wet granulation typically has several concurrent rate processes, including wetting and nucleation, particle coalescence and growth, consolidation, and attrition and breakage. Wet granulation remains one of the most widely used granulation methods, particularly in the pharmaceutical industry.
Types of Wet Granulation
Wet Granulation has a variety of different methods. The three most widely used mainstream technologies in industrial applications include High-Shear Granulation (HSG), Fluidized-Bed Granulation (FBG), and Twin-Screw Granulation (TSG).
Comparison of Mainstream Wet Granulation Technologies
High-Shear Granulation (HSG)
Working Principle
High-shear granulation is carried out in a sealed vessel containing a stirrer and a cutting blade. The dry powder is first thoroughly mixed by the agitator, while a liquid binder is simultaneously sprayed onto the powder bed through a nozzle. The combined action of the agitator’s high-speed rotation and the cutting blade causes the powder particles to be simultaneously crushed and mixed, forming dense agglomerates.
After the wet granules are formed, they must be transferred to additional drying equipment for drying.
Particle Characteristics
High-shear granulation produces particularly dense granules with a higher density than those produced by the fluidized-bed process. These granules have a high bulk density and excellent flow properties, and are commonly easy to compress into tablets.
Advantages
- High-shear granulation involves fewer operating parameters than fluidized-bed granulation, so the development workload during initial formulation research is relatively lighter.
- The produced particles have high density, good sphericality, and good flowability.
- The HSG production process is highly efficient and suitable for large-scale production.
Drawbacks
- Drying requires additional equipment, which increases the potential risks of equipment investment and process transfer.
- If your product requires a porous structure, then HSG is not the right choice.
- In some cases, this may affect tablet compressibility.
Fluidized-Bed Granulation (FBG)
Working Principle
In fluidized-bed granulation, heated air enters the powder bed from the bottom of the equipment through a distribution plate. The powder particles are lifted by the airflow and move in a boiling motion. A binder solution is sprayed onto the fluidized particles through nozzles, while the hot air continuously dries the particles, causing the solvent in the binder to evaporate rapidly and form solid bridges, resulting in the particles’ gradual growth.
In this process, mixing, granulation, and drying are all completed within a single piece of equipment.
Particle Characteristics
Compared to high-shear granulation, granules produced by fluidized-bed granulation are lighter (density typically around 0.25–0.29 g/cm³), looser, irregular in shape, and more porous, but exhibit better compressibility.
Advantages
- Since all the granulation processes (including drying) are completed in the same equipment, FBG has significantly reduced labor costs, minimized material transfer losses, and shortened processing time.
- FBG is more gentle towards heat-sensitive or brittle powders.
- The particles produced by FBG are porous, highly compressible, and have excellent solubility.
- The airflow, temperature, and adhesive spraying can be precisely controlled.
Drawbacks
- The initial investment for the equipment is relatively high.
- Optimizing process parameters requires a significant amount of preliminary development work.
- There is a risk of filter bag or burden nozzle blockage.
Twin-Screw Granulation (TSG)
Working Principle
Twin-screw granulation is a continuous wet granulation process based on a twin-screw extruder.
Powder enters the equipment through a feeding system, while a liquid binder is added at a designated point. Under the combined action of the twin screws’ conveying and shearing forces, the material undergoes mixing, wetting, nucleation, agglomeration, and particle growth. The resulting granules can then be fed into a continuous drying system. Or you can adopt other operations, such as melt granulation, as needed by the process.
Particle Characteristics
Granules produced by twin-screw granulation are irregularly elongated, porous, and loose. Although their flowability is not as good as that of granules produced by high-shear granulation, they offer superior compressibility, allowing for the production of tablets with higher strength using less compression force.
Advantages
- TSG has strong continuous production capabilities.
- Process parameters (such as liquid-to-solid ratio and screw speed) are easy to control, resulting in a narrow particle size distribution.
- Easy to integrate with PAT (Process Analytical Technology) and has a small footprint.
Drawbacks
- The process development and screw design require a considerable accumulation of professional knowledge.
- If you use a low-dose formulation, there may be uneven API distribution.
- The outcome of twin-screw granulation is highly dependent on the physical and chemical properties of the raw materials. Even minor differences in the formulation can have a significant impact on the final granules and product quality.
FAQ
What Is PAT? What Role Does It Play in Granulation Technology?
PAT (Process Analytical Technology) is a suite of tools used in granulation technology to monitor particle quality attributes in real time.
PAT methods include near-infrared spectroscopy, Raman spectroscopy, and online particle size analyzers. In continuous wet granulation technologies, PAT enables real-time analysis of key parameters such as particle size distribution, API content, and moisture content. It helps you promptly identify deviations and modify process parameters to improve process control and product quality stability.
What Is Melt Granulation? What Kind of Granulation Technology Does It Belong to?
Melt granulation is often considered a specialized granulation technique that has some similarities with wet granulation, as a molten binder acts as the binding phase. The principle involves heating a low-melting-point solid binder to form a molten liquid, which is then sprayed onto the surface of the particles. Upon cooling, the molten material solidifies into a bridging layer, thereby forming the granules.
This method is particularly suitable for drug components sensitive to organic solvents or water. It can also improve the dissolution profile and physical stability of the granules.
How Much Difference Is there in Processing Time between High-Shear Granulation and Fluidized-Bed Granulation?
Processing time varies depending on formulation properties, equipment configuration, and batch size.
According to a 2018 study on a certain formulation, the total batch time for the high-shear granulation process was 45 minutes. Since fluidized-bed granulation requires both granulation and drying to be completed simultaneously within the same equipment, the total time reached 107 minutes.
However, fluidized-bed granulation integrates the drying step into the same equipment, thereby reducing material transfer steps and potential problems. And it offers superior material efficiency compared to high-shear granulation.
How Can I Determine Whether My Product Is Better Suited for Wet or Dry Granulation Technology?
The main basis for judgment is the sensitivity of the material to moisture and heat. If the API is prone to degradation under humid or high-temperature conditions, dry granulation is more suitable for you. If the material requires improvement in flowability and compressibility, wet granulation is the preferred option. It is recommended that you carry out a pilot test first.
In Granulation Technology, How Can We Prevent the Separation of API and Excipients?
Granulation itself can reduce stratification. In wet granulation, the API and excipients are locked inside the granules through binders. In dry granulation, the components are closely combined through mechanical compaction. The main point is to ensure that the mixture is well mixed before granulation and that the particle size distribution is concentrated. In addition, the porous structure of the particles in fluidized bed granulation helps maintain the same.
Do Research and Production Necessarily Have to Use the Same Granulation Technology?
It is not mandatory, but consistency is strongly recommended. If fluidized-bed granulation is used in R&D and high-shear granulation is adopted during scale-up, the granule properties (density, porosity) will differ significantly, affecting tableting behavior. The advantage of continuous granulation technology (such as twin-screw granulation) is that production-grade equipment can be used directly in R&D, thereby reducing scale-up risks.
Final Thoughts
If you need any granulation or drying equipment, Pilotech is definitely your top choice. Pilotech is an experienced spray dryer manufacturer. We can also offer you spray granulation coating machines, vacuum belt dryers, and many other pieces of equipment. If you have any questions, please feel free to contact us.