Mixing Systems for Pharmaceutical Powders

Pharmaceutical powder mixing requires precise control of blend uniformity, segregation risk, containment and cleanability. Hosokawa Micron develops mixing systems for APIs and excipients, from low-shear blending in the Nauta^® conical screw mixer to medium- and high-shear processing with the Conical Paddle Mixer and Cyclomix. Depending on the process, systems can incorporate feeding, dosing, liquid addition, contained charging and discharge, CIP cleaning and SIP sterilisation.

Applications range from premixes and low-dose formulations to direct compression and dry powder inhalers. In tablet production, mixing is often followed by wet or dry granulation, while suitable formulations can be processed by direct compression. The appropriate mixer and process sequence depend on powder cohesion, differences in bulk density and particle size, the required mixing energy and relevant safety and regulatory requirements. Trials at the Test Centre help validate the process choice and support scale-up from R&D to production.

Wet and dry granulation

In tablet manufacturing, achieving a uniform blend is only part of the challenge. The formulation must also provide suitable flowability and compressibility, while maintaining content uniformity during discharge, transfer and feeding into the tablet press. Differences in particle size, bulk density and cohesion between APIs and excipients can increase the risk of segregation.

Wet granulation can improve flowability and compressibility, but typically involves additional steps such as liquid addition, granulation, drying and sizing. Dry granulation avoids liquid addition and may be preferable for moisture-sensitive formulations, although the formation of fines and the properties of the resulting granules must be considered.

Both approaches have their place, depending on the formulation and downstream processing requirements.

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 customised 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 such as de-agglomerators, sieves and cone mills can be integrated where required, for example to break down agglomerates or achieve the desired particle size distribution.

The conical vessel design and top-driven agitator of the Nauta^® conical screw mixer help minimise the risk of segregation during discharge. Depending on the plant layout, the mixer can be positioned directly above a tablet press, reducing intermediate handling and transfer steps. This configuration can help maintain blend uniformity throughout the process, subject to the characteristics of the formulation and the downstream equipment.