(49b) Influence of Filtration on Particle Size and Shape of Crystalline Material

The production process of pharmaceuticals and fine chemicals often includes a biotechnological synthesis. Subsequent, the target molecule has to be separated from the surrounding liquor selectively and with high purity. Therefore the crystallization is a common step in downstream processing. After the formation of the solid crystalline form, the material has to be separated from the broth using a solid-liquid-separation-step. During the separation the product is exposed to mechanical stress, which can lead to a modification of the outer appearance of the crystals.

In literature the impact of crystallization conditions, for example agitator speed or additional compounds, on the shape and agglomeration of crystalline particle systems is described [1,2]. Besides the formation of the solid phase, also the subsequent processing is influencing the particle form. Events which influence the shape of the particles can be either breakage of crystals or the formation of solid bridges due to solved compounds in the remaining liquid after mechanical dewatering. These changes in particle structure can have a high impact on solubility, bioavailability and further formulation properties of the final product [3,4]. By choosing the right separation device as well as the appropriate machine parameters, unfavorable changes in product shape can be decimated or in best case avoided. Therefore, the intensity of the following formulation steps can be reduced by adjusting the required product characteristics during the separation step.

In the following work, the influence of the separation on the crystal appearance is investigated. As criterion of the product quality the grade of agglomeration is evaluated. As model system for pharmaceutical and fine chemicals amino acids are used. For the quantification of the agglomeration grade of the crystalline systems an automated image analysis and classification was used based on literature [5,6]. The different classification methods of agglomerated and single crystals is applied to different system of crystalline amino acids.

Since this work focuses on the filtration as separation method, different types of filtration, for example pressure filtration and vacuum filtration are compared regarding the impact on the agglomeration degree as well as the particle size distribution. Automated image analysis was used to classify the crystals regarding their appearance. Therewith the grade of agglomeration before and after filtration was analysed and set into relation.

With this information the choice of the appropriate separation device can be complemented by the knowledge of the influence of the separation on the particle shape.

References

[1] D. Wieckhusen, CHIMIA 2006 60 (9), 598. DOI: 10.2533/chimia.2006.598.

[2] E.M. Ålander, M.S. Uusi-Penttilä, Å.C. Rasmuson, Ind. Eng. Chem. Res. 2004 43 (2), 629. DOI: 10.1021/ie0301280.

[3] S. Schmidt, D. Havekost, K. Kaiser, J. Kauling, H.-J. Henzler, Eng. Life Sci. 2005 5 (3), 273. DOI: 10.1002/elsc.200500116.

[4] N. Blagden, M. de Matas, P.T. Gavan, P. York, Advanced drug delivery reviews 2007 59 (7), 617. DOI: 10.1016/j.addr.2007.05.011.

[5] L.-M. Terdenge, S. Heisel, G. Schembecker, K. Wohlgemuth, Chemical Engineering Science 2015 133, 157. DOI: 10.1016/j.ces.2015.03.002.

[6] D.R. Ochsenbein, T. Vetter, S. Schorsch, M. Morari, M. Mazzotti, Crystal Growth & Design 2015 15 (4), 1923. DOI: 10.1021/acs.cgd.5b00094.