466054 Tuning the Properties of Crystalline Particles –Temperature Cycling in a Continuous Tubular Crystallizer

Tuesday, November 15, 2016: 8:55 AM
Cyril Magnin III (Parc 55 San Francisco)
Peter Neugebauer1, Maximilian Besenhard2 and Johannes G. Khinast2,3, (1)Institute for Process and Particle Engineering, Graz University of Technology, Graz, Austria, (2)Research Center Pharmaceutical Engineering GmbH, Graz, Austria, (3)Institute of Process and Particle Engineering, Graz University of Technology, Graz, Austria

Tuning the properties of crystalline particles –Temperature Cycling in a Continuous Tubular Crystallizer

P. Neugebauer1, M. Besenhard2, J.G. Khinast1,2

 

1 Graz University of Technology, Institute for Process and Particle Engineering, 8010 Graz, Austria

2 Research Center Pharmaceutical Engineering, 8010 Graz, Austria

 

Correspondence:

e-mail: peter.neugebauer@tugraz.at; tel: +43 (316) 873 - 30424

e-mail: khinast@tugraz.at; tel: +43 (316) 873 – 30400; fax: +43 (316) 873 - 1030400

 

 

The utility of tubular reactors for the continuous production of crystalline particles by now has been demonstrated for a wide range of different substrates. Mostly, these systems profit by the ease of supersaturation control by the installation of sections at different temperatures.

Experimental designs employing water baths or jackets have shown to be adequate to benefit from the high surface:volume ratio offered by tubular crystallizers, guaranteeing efficient heat flow from or to the crystallization slurry1–3.

 

In the present study we established an easy-to-use platform which allows the modification of crystals from ingredients of pharmaceutical interest under controlled conditions. Our installation facilitates easy changing of process settings such as flow rate, crystal loading and temperature trajectory. Simultaneously, it provides immediate results enabling us to experimentally test a broad range of settings in a short period of time.

 

Within our setup (Figure 1) a tubular crystallizer with hot and cold zones was shown to be adequate to oscillate dissolution and growth efficiently via temperature cycling. By this, the feasibility of crystal engineering could be shown for pharmaceutical ingredients. By establishing a segmented flow mode interfering effects such as aggregation and breakage could be minimized and by thorough characterization of the temperature cycler unwanted nucleation could be overcome.

 

Figure 1: Schematic drawing of the experimental setting

(1)      Neugebauer, P.; Khinast, J. G. Continuous Crystallization of Proteins in a Tubular Plug-Flow Crystallizer. Cryst. Growth Des. 2015, 15, 1089–1095.

(2)      Besenhard, M. O.; Neugebauer, P.; Da-Ho, C.; Khinast, J. G. Crystal Size Control in a Continuous Tubular Crystallizer. Cryst. Growth Des. 2015, 15, 1683–1691.

(3)      Jiang, M.; Zhu, Z.; Jimenez, E.; Papageorgiou, C. D.; Waetzig, J.; Hardy, A.; Langston, M.; Braatz, R. D. Continuous-Flow Tubular Crystallization in Slugs Spontaneously Induced by Hydrodynamics. Cryst. Growth Des. 2014, 14, 851–860.

 


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