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Agglomeration behavior of anhydrous L-ornithine-L-aspatate crystals during semi-batch drowning-out crystallization

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Abstract

Crystallization of L-ornithine-L-aspartate (LOLA) by drowning out was carried out to produce the anhydrous form of agglomerates. The primary crystal size in the agglomerate remained unchanged after completion of the crystallization. The LOLA aqueous solution introduced into the system was immediately dispersed and cluster coagulated on the surface of the crystals. On the surface of the crystals, a cluster reached critical nuclei size, nucleated and intergrowth to form agglomerates. It was proposed that a spherical agglomeration occurred during secondary nucleation by coagulation model and intergrowth. The agglomerates size and size distribution were varied with the process parameters. The agglomerate sizes of LOLA crystals appeared to be ruled not only by secondary nucleation rate but also by the mass of suspended agglomerates. Moreover, the agglomeration rates of fine particles were higher than the agglomeration rates of large agglomerates. Using these properties, the uniform agglomerates size distribution could be obtained.

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References

  • Brittain, H. G.,Polymorphism in pharmaceutical solids, Marcel Dekker, New York (1999).

    Google Scholar 

  • Charmolue, H. and Rousseau, R. W., “L-Serine obtained by methanol addition in batch crystallization,”AIChE J.,37, 1121 (1991).

    Article  CAS  Google Scholar 

  • Choe, J., Kwon, Y. and Kim, Y., “Micromixer as a continuous flow reactor for the synthesis of a pharmaceutical intermediate,”Korean J. Chem. Eng.,20, 268 (2003).

    Article  CAS  Google Scholar 

  • Chulia, D., Deleuil, M. and Pourcelot, Y.,Powder technology and pharmaceutical processes, Elsevier, Amsterdam (1994).

    Google Scholar 

  • David, A. B., Susan, R. D. and Ka, M. N., “Synthesis of drowning-out crystallization-based separations,”AIChE J.,43, 91 (1997).

    Article  Google Scholar 

  • Kage, H., Dohzaki, M. and Ogura, H., “Powder coating efficiency of small particles and their agglomeration in circulating fluidized bed,”KoreanJ. Chem. Eng.,16, 630 (1999).

    Article  CAS  Google Scholar 

  • Kawashima, Y., Okumura, M. and Takenaka, H., “Spherical crystallization: Direct spherical agglomeration of salicylic acid crystals during crystallization,”Science,216, 1127 (1982).

    Article  CAS  Google Scholar 

  • Kim, Y. H., Haam, S., Koo, K.-K., Shul, Y. G., Son, J. H. and Jung, J. K., “Representation of solid-liquid equilibrium of L-ornithine-L-aspartate+water+methanol system using the chen model for electrolyte solution,”J. Chem. Eng. Data,46, 1387 (2001).

    Article  CAS  Google Scholar 

  • Kim, Y. H., Haam, S., Shul, Y. G., Kim, W. S., Jung, J. K., Eun, H.-C. and Koo, K.-K., “Pseudopolymorphic crystallization of L-ornithine-L-aspartate by drowning out,”I&EC,42, 883 (2003).

    CAS  Google Scholar 

  • Kim, Y. H., Hyung, W. C., Haam, S. J. and Koo, K. K., “The effect of initial precipitates on the induction period of L-ornithine-L-aspartate during semi-batch drowning out crystallization,”J. of Crystal Growth, In press (2006).

  • Kim, Y., Haam, S. and Kim, W. S., “Parameters determining the agglomeration behavior of anhydrous L-ornithine-L-aspartate (LOLA) crystals prepared by drowning out crystallization,”Korean J. Chem. Eng.,20, 1111 (2003).

    Article  CAS  Google Scholar 

  • Mulline, J. W.,Crystallization, Butterworth-Heinemann, London (1993).

    Google Scholar 

  • Myerson, A. S.,Handbook of industrial crystallization, Butterworth-Heinemann, London (1993).

    Google Scholar 

  • Randolph, A. D. and Larson, M. A.,Theory of particulate processes, Academic press (1971).

  • Rees, C. J., Oppong, K., Al Mardini, H., Hudson, M. and Record, C. O., “Effect of L-ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: A double blind, placebo controlled trial,”Gut,47(4), 571 (2000).

    Article  CAS  Google Scholar 

  • Rose, C., Michalak, A., Pannunzio, P., Therrien, G., Quack, G., Kircheis, G. and Butterworth, R. F., “L-Ornithine-L-aspartate in experimental portal-systemic encephalopathy: Therapeutic efficacy and mechanism of action,”Metabolic Brain Disease,13(2), 147 (1998).

    Article  CAS  Google Scholar 

  • Rose, C., Michalak, A., Rao, K. V., Quack, G., Kircheis, G. and Butterworth, R. F., “L-Ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure,”Hepatology (Baltimore, Md.),30(3), 636 (1999).

    CAS  Google Scholar 

  • Szabó-Révész, P., GöczÕ, H., Pintye-Hódi, K., Kasa Jr, P., ErÕs, I., Hasznos-Nezdei, M. and Farkas, B., “Development of spherical crystal agglomerates of an aspartic acid salt for direct tablet making,”Powder Technology,114, 118 (2001).

    Article  Google Scholar 

  • Vogels, B. A., Karlsen, O. T., Mass, M. A., Boveé, W. M. and Chamuleau, R. A., “L-Ornithine vs. L-ornithine-L-aspartate as a treatment for hyperammonemia-induced encephalopathy in rats,”J. of Hepatology,26(1), 174 (1997).

    Article  CAS  Google Scholar 

  • Wolfgang, B., “Nucleation phenomena during the crystallization and precipitation of aecarnil,”J. of Crystal Growth,198–199, 1307 (1999).

    Google Scholar 

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Correspondence to Seungjoo Haam.

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Hyung, W., Kim, Y., Haam, S. et al. Agglomeration behavior of anhydrous L-ornithine-L-aspatate crystals during semi-batch drowning-out crystallization. Korean J. Chem. Eng. 23, 819–826 (2006). https://doi.org/10.1007/BF02705934

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  • DOI: https://doi.org/10.1007/BF02705934

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