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HAPILA has extensive know-how in the evaluation, development and optimisation of crystallisation processes for the purification of pharmaceutical ingredients and intermediates as well as fine chemicals. This makes us the ideal partner for solving problems regarding substance purification.

In order to further advance our technologies, we have a long-term cooperation with MPI Magdeburg »» (Max Plank Institute for Dynamics of Complex Technical Systems, Department of Physical and Chemical Foundations of Process Engineering), and with Jesalis Pharma GmbH »» opening up new prospects for demanding separation processes by crystallisation.

Based on the relationship specific to substance and process with regard to the depletion behaviour of impurities, we are able to optimise the crystallisation process in batch processing or, if required, develop a process using our patented HAPIpur® technology.

Here, we investigate the influence of different process parameters on the crystallisation progression by computer simulation to enable us to offer cost-efficient process development. To this, we offer our customers the step-by-step development of the processes in order to keep the risk low for both parties.

HAPIpur® technology

The HAPIpur® process of continuous counter current crystallisation provides a cost-efficient technology for the purification of solid chemical substances and, in particular, pharmaceutical ingredients. In comparison to other purification processes such as batch crystallisation or chromatography, the HAPIpur® technology is outstanding due to a significantly higher space-time yield.

This procedure is adapted to each specific purification task and sets new standards for cost efficiency and reproducibility both in pilot plant and production scale.


  • Achieving simultaneously extremely high purity with higher yield
  • fast process development as well as a simple scale-up by a universally applicable system concept
  • cost-efficient operation by full automation
  • exact process calculation for reproducible results
  • requires only low amounts of substance for the development
  • all processes undertaken on-site, no external manufacturing, - ideal for GMP “High Actives”
  • overall service from feasibility up to pilot-scale production
  • process / industrial scale equipment can be established at client’s site through separate agreement involving HAPILA - Büchi

    As with distillation and extraction, it is also possible for crystallisation to multiply the separating effects based on the balance of dispersal by continuous separation and combining the phases in the counter current, even though the technological implementation is significantly more difficult with crystallisation, because the phase transformation is a solid to liquid transfer. Therefore continuous counter current processes within the field of crystallisation of solutions could not so far the established as standard processes.

    With the multistage HAPIpur® process of the counter current crystallisation this obstacle has been overcome in a compact plant.

    Here the essential requirement is to influence the supersaturation of the solution and the grain growth to achieve not just a coarse, well separable crystalline material but also a maximal depletion of the impurities in a reproducible way.

    In the quasi-continuous crystallization process, the crystallized material and the mother liquor are handled in a counter current process without any external operation. All processing takes place (favourably) in solution. The solving and crystallization processes in the crystallizers are carried out in parallel and are time-synchronized - all resulting in a highly efficient process. Supersaturation during crystallization is adjusted by alternating heat and evaporation phases under vacuum for all concurrent and identical crystallizers. The growth in high purity of the crystals is supported by the oscillating temperature profile preventing the substance from sticking to the heater surface.

    This results in excellent reproducibility of both purification as well as yield in all phases of the crystallization process. In so doing, considerable steps for a successful process validation are achieved.



    U. Müller, R. Eilers, D. Grawe (2010).
    Purification of active pharmaceutical ingredients by continuous counter current crystallization
    Book of Proceedings of the 17th International Workshop on Industrial Crystallization, September 8-10, 2010, Martin Luther University Halle-Wittenberg, Halle, Germany (BIWIC 2010), pages 118-124,
    ISBN: 978-3-86955-428-0 »»

    Temmel, E., Wloch, S., Müller, U., Grawe, D., Eilers, R., Lorenz, H., & Seidel-Morgenstern, A. (2012).
    Continuous crystallization for separation of substances with solid solution behaviour.
    Poster presented at 3rd Granada International School of Crystallization 2012. Granada, Spain. 2012-05-21 - 2012-05-25.
    Download PDF »»

    Temmel, E., Wloch, S., Müller, U., Grawe, D., Eilers, R., Lorenz, H., & Seidel-Morgenstern, A. (2013).
    Separation of systems forming solid solutions using counter-current crystallization.
    Chemical Engineering Science, 104, 662-673. doi:10.1016/j.ces.2013.09.054.

    Temmel, E., Wloch, S., Müller, U., Grawe, D., Eilers, R., Lorenz, H., & Seidel-Morgenstern, A. (2013).
    Aufreinigung durch mehrstufige Gegenstromkristallisation zur Herstellung hochreiner Pharmazeutika.
    Chemie-Ingenieur-Technik, 85 (10), 1581-1588. doi:10.1002/cite.201200244.