Progressively frozen condensation crystallization of oxiracetam

doi:10.11949/j.issn.0438-1157.20150903

CIESC Journal ›› 2015, Vol. 66 ›› Issue (9): 3563-3569.DOI: 10.11949/j.issn.0438-1157.20150903

Progressively frozen condensation crystallization of oxiracetam

DU Shichao^1,2, LI Kangli^1,2, ZHANG Yu³, GAO Zhifeng³, WANG Chenguang³, GUO Baisong⁴, LI Daixi⁵, TANG Weiwei^1,2, GONG Junbo^1,2

1 The State Research Center of Industrialization for Crystallization Technology, School of Chemical Engineering, Tianjin University, Tianjin 300072, China;
2 Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, 300072, China;
3 Shijiazhuang Pharmaceutical Group Ou Yi Co., Ltd, Shijiazhuang 050051, Hebei, China;
4 Shanghai Tofflon Science & Technology Co., Ltd, Shanghai 201109, China;
5 University of Shanghai for Science and Technology, Shanghai 200093, China

Received:2015-06-11 Revised:2015-07-07 Online:2015-09-05 Published:2015-09-05
Supported by:
supported by the National Natural Science Foundation of China (NNSFC21176173, NNSFC21376164) and the National High Technology Research and Development Program of China (2012AA021202).

奥拉西坦的逐步冻凝结晶

杜世超^1,2, 李康丽^1,2, 张育³, 高志峰³, 王晨光³, 郭柏松⁴, 李代禧⁵, 汤伟伟^1,2, 龚俊波^1,2

1 国家工业结晶工程技术研究中心, 天津 300072;
2 天津化学化工协同创新中心, 天津 300072;
3 石药集团欧意药业有限公司, 河北石家庄 050051;
4 上海东富龙科技股份有限公司, 上海 201109;
5 上海理工大学, 上海 200093

通讯作者: 龚俊波
基金资助:
国家自然科学基金项目(NNSFC21176173,NNSFC21376164);国家高技术研究发展计划项目(2012AA021202)。

Abstract

Abstract:

It is found that direct freeze-drying method is not applicable to oxiracetam because of long time and poor product quality. In this paper, MS software is used to calculate the molecular interactions between additive (sorbitol) and different crystal surfaces of oxiracetam. These values are very small and could be neglected. Experiments also show that the crystal form and morphology are independent of sorbitol in freeze-drying process. Analyzed by differential scanning calorimetry and hot-stage microscopy, glassy sate of oxiracetam prescription is identified during original prefreezing process, against sublimation of water molecules. Therefore, we propose a gradual congelation crystallization technology to change the crystal state of sorbitol, congeal every component and separate them in microcrystalline. According to results of larger scale experiments, this new technique greatly shortens the time required and improves the product quality.

Key words: freeze drying, interaction energy, glass state, hot-stage microscopy, crystallization

摘要：

奥拉西坦简单冻干往往导致所需时间长、产品质量差等问题,本文应用MS软件计算了山梨醇和奥拉西坦晶体各个晶面的相互作用能,结果表明山梨醇和奥拉西坦之间的相互作用能较小,实验也证明冻干过程中奥拉西坦晶型、晶习不受山梨醇影响。通过DSC和热台显微镜分析,奥拉西坦简单冻干问题的关键因素在于原预冻过程处方逐步冻凝产生的是玻璃态,不利于水分子升华干燥,因此本文提出奥拉西坦冻干过程的逐步冻凝结晶工艺,改变山梨醇的结晶状态,使各组分分别冻凝分离成微晶态,实验放大结果表明冻干所需时间大幅度缩短,产品质量得到很大提高。

关键词: 冻干, 相互作用能, 玻璃态, 热台显微镜, 结晶

CLC Number:

O799

DU Shichao, LI Kangli, ZHANG Yu, GAO Zhifeng, WANG Chenguang, GUO Baisong, LI Daixi, TANG Weiwei, GONG Junbo. Progressively frozen condensation crystallization of oxiracetam[J]. CIESC Journal, 2015, 66(9): 3563-3569.

杜世超, 李康丽, 张育, 高志峰, 王晨光, 郭柏松, 李代禧, 汤伟伟, 龚俊波. 奥拉西坦的逐步冻凝结晶[J]. 化工学报, 2015, 66(9): 3563-3569.

References 21

[1]	Belfiore P, Ponzio F, Biagetti R, Berettera C, Magnani M, Pozzi O. Oxiracetam prevents the hippocampal cholinergic hypofunction induced by the NMDA receptor blocker AP7 [J]. Neuroscience Letters, 1992, 143 (1): 127-130.
[2]	Spignoli G, Pepeu G. Oxiracetam prevents electroshock- induced decrease in brain acetylcholine and amnesia [J]. European Journal of Pharmacology, 1986, 126 (3): 253- 257.
[3]	Saletu B, Linzmayer L, Grünberger J, Pietschmann H. Double-blind, placebo-controlled, clinical, psychometric and neurophysiological investigations with oxiracetam in the organic brain syndrome of late life [J]. Neuropsychobiology, 1985, 13 (1/2): 44-52.
[4]	Ye Lei. (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide racemate crystal form ii and preparation method therefor [P]: US, 14/237894. 2012-4-24.
[5]	Iriuchijima S, Kobayashi H, Aoki K, et al. Process for producing oxiracetam [P]: U.S, 4686296. 1987-8-11.
[6]	Wang Z Z, Chen J M, Lu T B. Enhancing the hygroscopic stability of S-oxiracetam via pharmaceutical cocrystals [J]. Crystal Growth & Design, 2012, 12(9): 4562-4566.
[7]	Mellor J D. Fundamentals of Freeze-Drying [M]. London: Academic Press Inc. Ltd., 1978.
[8]	Pikal M J. Freeze-drying of proteins. Process, formulation, and stability [J]. ChemInform, 1995, 26(4). DOI: 10.1002/chin.199504315.
[9]	Liapis A I, Pim M L, Bruttini R. Research and development needs and opportunities in freeze drying [J]. Drying Technology, 1996, 14 (6): 1265-1300.
[10]	Yu Jianping, Liu J H, Pu L Q, Cui Xiangdong, Wang Changzheng, Ouyang S L, Gao Dayong. Freeze-drying of human red blood cells: influence of carbohydrates and their concentrations [J]. Cell Preservation Technology, 2004, 2 (4): 270-275.
[11]	Zhou Xinli (周新丽), Liu Jianfeng (刘建峰), Zhang Shaozhi (张绍志), Chen Guangming (陈光明). Thermal analysis on lyoprotectants for biomaterials [J] Journal of Refrigeration (制冷学报), 2008, 29 (5): 54-57.
[12]	Wang Jingkang (王静康). Crystallization (结晶)//Shi Jun (时钧), Wang Jiading (汪家鼎), Yu Kuo Tsung (余国琮), Chen Minheng (陈敏恒). Handbook of Chemical Engineering (化学工程手册) [M]. Beijing: Chemical Industry Press. 1996.
[13]	Dubochet J, Chang J J, Freeman R, Lepault J, McDowall A W. Frozen aqueous suspensions [J]. Ultramicroscopy, 1982, 10 (1): 55-61.
[14]	Liu H, Lelièvre J. Transitions in frozen gelatinized-starch systems studied by differential scanning calorimetry [J]. Carbohydrate Polymers, 1992, 19 (3): 179-183.
[15]	Varshney D B, Kumar S, Shalaev E Y, Kang S W, Gatlin L A, Suryanarayanan R. Solute crystallization in frozen systems-use of synchrotron radiation to improve sensitivity [J]. Pharmaceutical Research, 2006, 23 (10): 2368-2374.
[16]	Zhu Liang(朱亮). Effects of pre-freeze in the freeze drying process [J]. Drying Technology & Equipment (干燥技术与设备), 2014, 12 (1): 32-34.
[17]	López-Urueña E, Alvarez M, Gomes-Alves S, et al. Tolerance of brown bear spermatozoa to conditions of pre-freezing cooling rate and equilibration time [J]. Theriogenology, 2014, 81 (9): 1229-1238.
[18]	Gao Zhifeng(高志峰). A freeze-dried powder and preparation method of oxiracetam [P]: CN, 102274195 A. 2011-07-18.
[19]	Yani Y, Chow P S, Tan R B H. Molecular simulation study of the effect of various additives on salbutamol sulfate crystal habi [J]. Molecular pharmaceutics, 2011, 8 (5): 1910-1918.
[20]	Schmidt C, Ulrich J. Morphology prediction of crystals grown in the presence of impurities and solvents-an evaluation of the state of the art [J]. Journal of Crystal Growth, 2012, 353 (1): 168-173.
[21]	Gupta P, Thilagavathi R, Chakraborti A K, Bansal A K. Role of molecular interaction in stability of celecoxib-PVP amorphous systems [J]. Molecular Pharmaceutics, 2005, 2 (5): 384-391.

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Progressively frozen condensation crystallization of oxiracetam

奥拉西坦的逐步冻凝结晶

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