Parameters Determining the Agglomeration Behavior of Anhydrous L-ornithine-L-aspartate (LOLA) Crystals Prepared by Drowning Out Crystallization

Yehoon Kim; Seungjoo Haam; Woo-Sik Kim; Kee-Kahb Koo

Korean Journal of Chemical Engineering, Vol.20, No.6, 1111-1117, November, 2003

Yehoon Kim, Seungjoo Haam^†, Woo-Sik Kim , and Kee-Kahb Koo¹

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

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Crystallization of L-ornithine-L-aspartate (LOLA) by drowning out was performed for the production of the anhydrous form of LOLA. The needle-like LOLA crystals were formed and spherically agglomerated during precipitation in a semibatch crystallizer. The primary crystal size in the agglomerate remains unchanged after completion of the crystallization. Therefore, the agglomeration process of primary crystals played an important role for controlling LOLA crystal size. The agglomeration of LOLA crystals was governed by not only the physico-chemical parameters such as the temperature and feed concentration, but also the hydrodynamic parameters such as agitation speed and feeding rate. The crystal size and the shape have been shown to be important factors in product impurity and flowability. Thus, the optimum condition of LOLA crystallization process by drowning-out 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., 37, 1121 (1991)
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)
Han HK, Lee SI, Lee CS, Korean J. Chem. Eng., 10(2), 100 (1993)
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, Ind. Eng. Chem., 42, 883 (2003)
Myerson AS, "Handbook of Industrial Crystallization," Butterworth-Heinemann, London (1993)
Mulline JW, "Crystallization," Butterworth-Heinemann, London (1993)
Randolph AD, Larson MA, "Theory of Particulate Processes," Academic Press (1971)
Rees CJ, Oppong K, AlMardini 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. Hepatology, 26(1), 174 (1997)
Wolfgang B, J. Cryst. Growth, 198-199, 1307 (1999)

[Referenced By]

[Related Articles]

[1] Brittain HG, "Polymorphism in Pharmaceutical Solids," Marcel Dekker, New York (1999)

[2] Charmolue H, Rousseau RW, AIChE J., 37, 1121 (1991)

[3] Chulia D, Deleuil M, Pourcelot Y, "Powder Technology and Pharmaceutical Processes," Elsevier, Amsterdam (1994)

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

[5] Han HK, Lee SI, Lee CS, Korean J. Chem. Eng., 10(2), 100 (1993)

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

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

[8] Kim YH, Haam S, Shul YG, Kim WS, Jung JK, Eun HC, Koo KK, Ind. Eng. Chem., 42, 883 (2003)

[9] Myerson AS, "Handbook of Industrial Crystallization," Butterworth-Heinemann, London (1993)

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

[11] Randolph AD, Larson MA, "Theory of Particulate Processes," Academic Press (1971)

[12] Rees CJ, Oppong K, AlMardini H, Hudson M, Record CO, Gut, 47(4), 571 (2000)

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

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

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

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

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