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

Woochan Hyung; Yehoon Kim; Seungjoo Haam; Kee-Kahb Koo

Korean Journal of Chemical Engineering, Vol.23, No.5, 819-826, September, 2006

DOI10.1007/BF02705934 Export Citation

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

Woochan Hyung, Yehoon Kim, Seungjoo Haam^†, and Kee-Kahb Koo¹

Department of Chemical Engineering, Yonsei University, Seoul 120-749, Korea
¹Department of Chemical and Biomolecular Engineering, Sogang University, Seoul 121-742, Korea

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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.

Keywords:Drowning-Out;L-Ornithine-L-Aspartate;Pseudopolymorph;Agglomeration;Impurity

[References]

Brittain HG, Polymorphism in pharmaceutical solids, Marcel Dekker, New York (1999)
Charmolue H, Rousseau RW, AIChE J., 3, 1121 (1991)
Choe J, Kwon Y, Kim Y, Song HS, Song KH, Korean J. Chem. Eng., 20(2), 268 (2003)
Chulia D, Deleuil M, Pourcelot Y, Powder technology and pharmaceutical processes, Elsevier, Amsterdam (1994)
Berry DA, Dye SR, Ng KM, AIChE J., 43(1), 91 (1997)
Kage H, Dohzaki M, Ogura H, Matsuno Y, Korean J. Chem. Eng., 16(5), 630 (1999)
Kawashima Y, Okumura M, Takenaka H, Science, 216, 1127 (1982)
Kim YH, Haam S, Koo KK, Shul YG, Son JH, Jung JK, J. Chem. Eng. Data, 46, 1387 (2001)
Kim YH, Haam S, Shul YG, Kim WS, Jung JK, Eun HC, Koo KK, “Pseudopolymorphic crystallization of L-ornithine-L-aspartate by drowning out,” I&EC, 42, 883 (2003)
Kim YH, Hyung WC, Haam SJ, Koo KK, “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, Kim WS, Koo KK, Korean J. Chem. Eng., 20(6), 1111 (2003)
Mulline JW, Crystallization, Butterworth-Heinemann, London (1993)
Myerson AS, Handbook of industrial crystallization, Butterworth-Heinemann, London (1993)
Randolph AD, Larson MA, Theory of particulate processes, Academic press (1971)
Rees CJ, Oppong K, Al Mardini H, Hudson M, Record CO, Gut, 47(4), 571 (2000)
Rose C, Michalak A, Pannunzio P, Therrien G, Quack G, Kircheis G, Butterworth RF, Metabolic Brain Disease, 13(2), 147 (1998)
Rose C, Michalak A, Rao KV, Quack G, Kircheis G, Butterworth RF, Hepatology, 30(3), 636 (1999)
Szabo-Revesz P, Goczo H, Pintye-Hodi K, Kasa P, Eros I, Hasznos-Nezdei M, Farkas B, Powder Technol., 114(1-3), 118 (2001)
Vogels BA, Karlsen OT, Mass MA, Bovee WM, Chamuleau RA, J. Hepatol., 26(1), 174 (1997)
Wolfgang B, J. Cryst. Growth, 198-199, 1307 (1999)

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[1] Brittain HG, Polymorphism in pharmaceutical solids, Marcel Dekker, New York (1999)

[2] Charmolue H, Rousseau RW, AIChE J., 3, 1121 (1991)

[3] Choe J, Kwon Y, Kim Y, Song HS, Song KH, Korean J. Chem. Eng., 20(2), 268 (2003)

[4] Chulia D, Deleuil M, Pourcelot Y, Powder technology and pharmaceutical processes, Elsevier, Amsterdam (1994)

[5] Berry DA, Dye SR, Ng KM, AIChE J., 43(1), 91 (1997)

[6] Kage H, Dohzaki M, Ogura H, Matsuno Y, Korean J. Chem. Eng., 16(5), 630 (1999)

[7] Kawashima Y, Okumura M, Takenaka H, Science, 216, 1127 (1982)

[8] Kim YH, Haam S, Koo KK, Shul YG, Son JH, Jung JK, J. Chem. Eng. Data, 46, 1387 (2001)

[9] Kim YH, Haam S, Shul YG, Kim WS, Jung JK, Eun HC, Koo KK, “Pseudopolymorphic crystallization of L-ornithine-L-aspartate by drowning out,” I&EC, 42, 883 (2003)

[10] Kim YH, Hyung WC, Haam SJ, Koo KK, “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)

[11] Kim Y, Haam S, Kim WS, Koo KK, Korean J. Chem. Eng., 20(6), 1111 (2003)

[12] Mulline JW, Crystallization, Butterworth-Heinemann, London (1993)

[13] Myerson AS, Handbook of industrial crystallization, Butterworth-Heinemann, London (1993)

[14] Randolph AD, Larson MA, Theory of particulate processes, Academic press (1971)

[15] Rees CJ, Oppong K, Al Mardini H, Hudson M, Record CO, Gut, 47(4), 571 (2000)

[16] Rose C, Michalak A, Pannunzio P, Therrien G, Quack G, Kircheis G, Butterworth RF, Metabolic Brain Disease, 13(2), 147 (1998)

[17] Rose C, Michalak A, Rao KV, Quack G, Kircheis G, Butterworth RF, Hepatology, 30(3), 636 (1999)

[18] Szabo-Revesz P, Goczo H, Pintye-Hodi K, Kasa P, Eros I, Hasznos-Nezdei M, Farkas B, Powder Technol., 114(1-3), 118 (2001)

[19] Vogels BA, Karlsen OT, Mass MA, Bovee WM, Chamuleau RA, J. Hepatol., 26(1), 174 (1997)

[20] Wolfgang B, J. Cryst. Growth, 198-199, 1307 (1999)