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Integrated process solutions for the pharmaceutical industry

Although the pharmaceutical industry is very innovative in terms of product development it is quite conservative in production philosophy. The current production philosophy has been around for a long time, is well understood and is accepted and validated.

Still, due to increasing necessity to reduce cost, the pharma industry has started to look into alternative manufacturing concepts. Based on the experience in many other process industries continuous manufacturing is explored by industry and academia. The idea of continuous operation, based on known input and understood process parameters the output is predictable which is key in life sciences. Therefore regulatory authorities like the FDA are favoring continuous process development.

The benefits sought in continuous manufacturing are:

  • Compactness. Smaller footprint of equipment requiring less infrastructure
  • Reduction of capital expenditures
  • Reduction of operational cost
  • Reduction of inventories
  • Avoid scaling up effects

To implement continuous production technologies in the pharmaceutical industry a profound understanding of all attributes is essential. Cooperation between academia and industry working on QbD (Quality by Design) and PAT (Process analytical Technology) is ongoing.

In most cases production of the ingredients like the API and excipients and formulation of final products like tableting are separated. Due to the nature of the technologies and our experience Hosokawa concentrates at first instance on the secondary process, mainly on tableting processes. The Hosokawa Group can provide integrated processes including milling, mixing and compaction of the powders before the tablets are pressed.

A typical process for direct compression consists of a number of processes which can be combined as modules. First of all the powders must be in the specified fineness by milling or micronization. Various milling technologies are available like impact mills or jet mills with or without integrated classifier. Milling technology is in its nature continuous and can therefore be integrated in the production line. Sensors for automatic detection of particle size distribution (PSD) can be integrated.

315 UPZ fine impact mill

For example, the 315 UPZ fine impact mill is designed for continuous processing – ensures stable milling conditions and product quality with controlled product fineness, capacity and temperature. The unit is also suitable for integration in CIP systems.

In the next stage, the API will be mixed with excipients. Since the APIs in particular normally have very bad flowing properties, an intensive mixing process is required, still without causing attrition effects. The Modulomix continuous pharma blender is a versatile unit designed for a minimum holdup of product in order to minimize the losses at start and end of the production run and for fast response to process variations.

Modulomix continuous pharma blender

By tuning the process parameters the technology is also capable of mixing lubricants like magnesium stearate gently in the formulated mixture. The product is now ready to go into the tablet press.

The homogeneousness of the mixture can be measured at the outlet of a mixer by NIR technology including facilities for on- and offspec material.

In case the product properties require so (bad flowing properties) or in case the products tend to segregate a compaction step can be added between the two mixing processes. Hosokawa's product range includes several roller compactor models with proven track records. After compaction the oversize material will be crushed or milled.

Pharmapaktor

In a continuous product line feeding the material in the various processing systems is vital. A range of volumetric as well as gravimetrical feeders can be used.

In case of high active products and hazardous handling we can also offer various levels of containment solutions.


Bert Dekens

Author:
Ing. Bert Dekens
Application Manager Pharma
Hosokawa Micron B.V.

+31 314 373 376

SUSTAINABLE PROCESSING SYSTEMS

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 7% of companies rated by EcoVadis in the special machinery industry.

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