Process technologies for tomorrow.


In large-scale tablet production, many pharmaceutical manufacturers utilize wet or dry granulation to minimize the risk of ingredient segregation. Direct compression offers a simpler and more cost-effective alternative, but requires adjustments to strictly defined and documented procedures. The time, money, and administrative effort involved often discourage this switch. However, the time and cost savings achieved by using a Nauta® mixer can make this transition worthwhile.


Tablets are the most common dosage form for medicines and require high quality standards to ensure that each tablet contains the correct ratio of Active Pharmaceutical Ingredients (APIs) and excipients such as binders, lubricants, flavourings or pigments. To achieve this, the components must be optimally mixed before being pressed into tablets.

Many manufacturers use tumbler or container mixers, followed by wet or dry granulation to prevent segregation. However, Hosokawa Micron's Nauta mixer offers the best of both worlds. By combining direct compression with the avoidance of segregation, it can eliminate the need for granulation, thus saving pharmaceutical manufacturers time and money.

By reducing the differences in bulk density and particle size distribution between APIs and excipients, the risk of segregation is minimized. Manufacturers often implement a granulation step to mitigate this risk. Wet granulation involves several steps such as granulation, drying and screening. This makes it a time-consuming and therefore costly process.

Alternatively, dry granulation is used, especially when the product to be granulated is sensitive to moisture and heat. Although dry granulation is simpler and therefore less costly, it can produce a higher percentage of fine granules which may compromise tablet quality.


Fine impact mill on top of a Nauta mixer Fine impact mill on top of a Nauta mixer

Direct compression is becoming increasingly popular as a simpler and cheaper alternative to granulation techniques. It involves mixing dry, free-flowing powders of uniform particle size for direct compression in a tablet press. For companies who are looking to eliminate the granulation step, Hosokawa Micron has the solution: the Nauta mixer.

The Nauta conical screw mixer is ideal for low-shear mixing of delicate free-flowing powders. It allows all the necessary ingredients to be blended into a completely homogeneous mixture to ensure uniform and highly accurate dosing. In addition, the Nauta is hugely flexible in terms of the filling volume, producing excellent mixing results even when the mixer is only 10% full. This also makes it suitable for use in a multi-stage mixing process to produce low-dose tablets.


At Hosokawa Micron, rather than just supplying machines, we like to take a broader approach to designing a total mixing solution, including pre- and post-processes. We always consider four aspects: how the powder is fed into the mixer, what happens inside the vessel, how the powder is discharged, and how the equipment is cleaned. For example, for the charging and discharging of toxic materials, we can use or develop customized container docking systems including lift systems or split butterfly valves.

During the mixing process, we account for any ingredients the customer may need to add and how they will affect the process. This includes liquids, which can even be heated or cooled during mixing if necessary. Post-processing equipment can be integrated if required, such as de-agglomeration equipment, sieves, and cone mills to return the mixture to powder form.

The conical vessel and top-driven agitator ensure that the powders do not segregate again during discharge into a tablet press, which can be a problem when using a container mixer. A Nauta mixer can even be positioned directly above a tablet press, to ensure direct discharge which further contributes to maintaining product stability.

Cleaning is extremely important in the pharmaceutical industry, which is why Hosokawa Micron offers complete automated cleaning in place (CIP) and sterilization in place (SIP) installations, including the associated control systems. Our CIP and SIP skids remain permanently docked. Eliminating the handling step reduces the risk of product contamination and greatly improves operator safety, especially with toxic materials.

Needless to say, all our systems comply with regulations and guidelines and include the necessary documentation, easing the regulatory burden on customers.


Cyclomix lab mixer for pharmaceutical powders Cyclomix lab mixer for pharmaceutical powders

Time is of the essence for manufacturers seeking to win the race to market and secure the all-important patent for a new and original pharmaceutical product. In order to have enough time to maximize the cost-saving potential of switching to direct compression, manufacturers should engage with Hosokawa Micron as early on as possible – preferably during the R&D process. Since each new tablet formulation is unique, we develop product-specific solutions together with each customer.

For example, it may be advantageous to prepare the premixes and then add the excipients all in the same mixer, rather than splitting the process into separate steps, and that's exactly what the Nauta mixer facilitates. At our Test Centre in the Netherlands, we often work closely with customers to investigate such possibilities using the actual ingredients in real-life, small-scale trials.

Direct compression can also benefit manufacturers of generic pharmaceutical products by reducing costs, even if it means redesigning production processes and revalidating procedures. The cost savings achieved without compromising quality make this approach worth considering.


Cyclomix high shear mixer Cyclomix high shear mixer

Hosokawa Micron has extensive experience in developing scalable technologies for the pharmaceutical industry, from R&D to large-scale manufacturing systems. In addition to the Nauta mixer, the company offers the Conical Paddle Mixer (CPM) for medium-shear mixing and the Cyclomix, which is widely used for high shear mixing of cohesive dry powder inhalers (DPI).

The required mixing energy depends on a number of factors such as powder characteristics (including material cohesion and particle size), end product properties, and process, safety and system requirements. Hosokawa Micron, with its extensive experience and proprietary technology, provides tailor-made mixing solutions for each customer's needs.


To learn more about our powder processing equipment and systems for mixing pharmaceutical powders, contact us:



Hosokawa Micron B.V. is certified according to ISO 14001. Our certification covers all environmental themes of ISO 14001: air, soil, energy, waste, water, noise and hazardous substances. In addition, Hosawa Micron was awarded an EcoVadis Silver Medal for its sustainability achievements. EcoVadis determined that the company was among the top 15% of companies rated by EcoVadis in the special machinery industry.

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