(286b) Tuning the Properties of Crystalline Particles –Temperature Cycling in a Continuous Tubular Crystallizer

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

P.
Neugebauer¹, M. Besenhard², J.G. Khinast^1,2

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 slurry^1–3.

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.