Controlled Crystallization During Freeze-Drying - Pharmaceutical Technology

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Controlled Crystallization During Freeze-Drying
The authors discuss the preparation of lipophilic drug nanocrystals by controlled crystallization during freeze-drying.

Pharmaceutical Technology
Volume 35, Issue 8, pp. 58-62


By using in-line Raman spectroscopy, it was shown that during the freezing step of the CCDF process only the solvents crystallized. The solutes did not crystallize until the temperature in the freeze-dryer was increased. Furthermore, the three-way nozzle can be used to alter the small-batch process into a semicontinuous process that is suitable for large-scale production. Controlled crystallized dispersions prepared by the semicontinuous process results in even smaller nanocrystals due to a higher freezing rate. Therefore, the semicontinuous process is not only suitable for large-scale production, but can also result in a better product.

Hans de Waard* is postdoctoral researcher, Niels Grasmeijer is a doctoral student, Wouter L.J. Hinrichs is senior researcher, and Professor Henderik W. Frijlink is chairman, all at the Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands, tel. +31 50 363 2397, fax +31 50 363 2500,
. Professor Thomas De Beer is a professor in the Laboratory of Pharmaceutical Process Analytical Technology at the Department of Pharmaceutical Analysis, Ghent University.

*To whom all correspondence should be addressed.

Submitted: Feb. 11, 2011. Accepted: Apr. 27, 2011.


1. C.A. Lipinski et al., Adv. Drug Deliv. Rev. 46 (1–3), 3–26 (2001).

2. G.L. Amidon et al., Pharm. Res. 12 (3), 413–420 (1995).

3. W. Curatolo, Pharm. Sci. Tech. Today 1 (9), 387–393 (1998).

4. D. Hou et al., Biomaterials 24 (10), 1781–1785 (2003).

5. A.A. Noyes and W.R. Whitney, J. Am. Chem. Soc. 19 (12), 930–934 (1897).

6. C.M. Keck and R.H. Muller, Eur. J. Pharm. Biopharm. 62 (1), 3–16 (2006).

7. B.Y. Shekunov et al., Pharm. Res. 23 (1), 196-204 (2006).

8. H. de Waard, W.L.J. Hinrichs, and H.W. Frijlink, J. Control. Release 128 (2), 179–183 (2008).

9. D.J. van Drooge, W.L.J. Hinrichs, and H.W. Frijlink, J. Pharm. Sci. 93 (3), 713–725 (2004).

10. R.L. McCreery, Raman Spectroscopy for Chemical Analysis, (Wiley-Interscience, New York, 1st ed., 2000).

11. H. de Waard et al., Eur. J. Pharm. Sci. 38 (3), 224–229 (2009).

12. J. Hu et al., Pharm. Res. 19 (9), 1278-1284 (2002).

13. M.J. Pikal, "Freeze drying" in Encyclopedia of Pharmaceutical Technology, J. Swarbrick, ed. (New York, Informa Healthcare USA, 2007).

*This article is based on a presentation given at the 7th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology (PBP World Meeting) in Malta 2010.

Citation: When referring to this article, please cite it as "H. de Waard, N. Grasmeijer, W.L.J. Hinrichs, T. De Beer, H.W. Frijlink, "Controlled Crystallization During Freeze-Drying," Pharmaceutical Technology 35 (8) 58-62(2011)."


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