Tuning the Morphology of Pharmaceutical Compounds via Model Based Solvent Selection

摘要/Abstract

摘要： In this paper we present a strategy for tuning the crystal morphology of pharmaceutical compounds by the appropriate choice of solvent via an optimization model.A three-stage approach involving a pre-design stage,a product design stage and a post-design experimental verification stage is presented.The pre-design stage addresses the formulation of the property constraint for crystal morphology.This involves crystallization experiments and development of property models and constraints for morphology.In the design stage various property requirements for the solvent along with crystal morphology are considered and the product design problem is formulated as a mixed integer nonlinear programming model.The design stage provides an optimal solvent/list of candidate solvents. Similar to the pre-design stage,in the post design experimental verification stage,the morphology of the crystals (precipitated from the designed solvent)is verified through crystallization experiments followed by product characterization via scanning electron microscopy,powder X-ray diffraction imaging and Fourier transform spectra analysis.

关键词: morphology, solvent selection, nonlinear programming, crystallization, product design

Abstract: In this paper we present a strategy for tuning the crystal morphology of pharmaceutical compounds by the appropriate choice of solvent via an optimization model.A three-stage approach involving a pre-design stage,a product design stage and a post-design experimental verification stage is presented.The pre-design stage addresses the formulation of the property constraint for crystal morphology.This involves crystallization experiments and development of property models and constraints for morphology.In the design stage various property requirements for the solvent along with crystal morphology are considered and the product design problem is formulated as a mixed integer nonlinear programming model.The design stage provides an optimal solvent/list of candidate solvents. Similar to the pre-design stage,in the post design experimental verification stage,the morphology of the crystals (precipitated from the designed solvent)is verified through crystallization experiments followed by product characterization via scanning electron microscopy,powder X-ray diffraction imaging and Fourier transform spectra analysis.

Key words: morphology, solvent selection, nonlinear programming, crystallization, product design

Arunprakash T. Karunanithi, Charles Acquah, Luke E. K. Achenie. Tuning the Morphology of Pharmaceutical Compounds via Model Based Solvent Selection[J]. , 2008, 16(3): 465-473.

Arunprakash T. Karunanithi, Charles Acquah, Luke E. K. Achenie. Tuning the Morphology of Pharmaceutical Compounds via Model Based Solvent Selection[J]. , 2008, 16(3): 465-473.

参考文献

1 Mullin, J.W., Crystallization, Butterworths, England(1961).
2 Davey, R.J., Whiting, M.J.L., “Habit modification of succinic acid crystals grown from different solvents”, J. Crystal Growth, 58, 304-312(1982).
3 Holmback, X., “Drowning out crystallization of benzoic acid:Influence of processing conditions and solvent composition on crystal size and shape”, Ph.D. Thesis, Department of Chemical Engineering, KTH, Stockholm(2002).
4 Cano, H., Gabas, N., Canselier, J.P., “Experimental study on the ibuprofen crystal growth morphology in solution”, J. Crystal Growth, 224, 335-341(2001).
5 Winn, D., Doherty, M.F., “Modeling crystal shapes of organic materials grown from solution”, AIChE J., 46, 1348-1367(2000).
6 Gordon, R.E., Amin, S.I., “Crystallization of Ibuprofen”, US Pat., 4476248(1984).
7 Rasenack, N., Muller, B.W., ”Properties of ibuprofen crystallized under various conditions:A comparative study”, Drug Dev. Ind. Pharm., 28(9), 1077-1089(2002).
8 Garekani, H.A, Sadeghi, F., Badiee, A., Mostafa, S.A., Rajabi-Siahboomi, A.R., “Crystal habit modifications of ibuprofen and their physicomechanical characteristics”, Drug Dev. Ind. Pharm., 27, 803-809(2001).
9 Duvedi, A.P., Achenie, L.E.K., “Designing environmentally safe refrigerants using mathematical programming”, Chem. Eng. Sci., 51(15), 3727-3739(1996).
10 Karunanithi, A.P.T., Achenie, L.E.K., Gani, R., “A new decomposition based solution methodology for the design of optimal solvents and solvent mixtures”, Ind. Eng. Chem. Res., 44(13), 4785-4797(2005).
11 Harper, P.M., “A multi-phase multi level framework for computer aided molecular design”, Ph.D. Thesis, Technical University of Denmark, Lyngby, Denmark(2000).
12 Lahav, M., Leiserowitz, L., “The effect of solvent on crystal growth and morphology”, Chem. Eng. Sci., 56, 2245-2253(2001).
13 Gavezzoti, A., Filippini, G., Kroon, J., Van Eijck., Klewinghaus, P., “The crystal polymorphism of tetrolic acid:A molecular dynamics study of precursors in solution and crystal structure generation”, Chem. Eur. J., 3, 893-899(1997).
14 Charifson, P.S., Practical Application of Computer-Aided Drug Design, Marcel Dekker Inc., New York(1997).
15 Parrill, A.L., Reddy, M., Rational Drug Design:Novel Methodology and Practical Applications(ACS Symposium Series 719), American Chemical Society, USA(1999).
16 Achenie, L.E.K., Gani, R., Venkatasubrmaniam, V., Computer Aided Molecular Design:Theory and Practice, Elsevier Science, Amsterdam(2003).
17 Venkatasubramaniam, V., Chan, K., Caruthers, J.M., “Computer aided molecular design using genetic algorithms”, Comput. Chem. Eng., 18, 833-844(1994).
18 Gani, R., Brignole, E.A., ”Molecular design of solvents for liquid extraction based on UNIFAC”, Fluid Phase Equilib., 13, 331(1983).
19 Macchietto, S., Odele, O., Omatsone, O., “Design of optimal solvents for liquid-liquid extraction and gas absorption processes”, Trans. Inst. Chem. Eng., 68, 429-433(1990).
20 Naser, S.F., Fournier, R.L., “A system for the design of an optimum liquid-liquid extractant molecule”, Comput. Chem. Eng., 15(6), 397-414(1991).
21 Pretel, E.J., Lopez, P.A., Bottini, S.B., Brignole, E.A., “Computer-aided molecular design of solvents for separation processes”, AIChE J., 40(8), 1349-1360(1994).
22 Wang, Y., Achenie, L.E.K., “Computer aided solvent design for extractive fermentation”, Fluid Phase Equilib., 201(1), 1-18(2002).
23 Churi, N., Achenie, L.E.K., “Novel mathematical programming model for computer aided molecular design”, Ind. Eng. Chem. Res., 35(10), 3788-3794(1996).
24 Chavali, S., Lin, B., Miller, D.C., Camarda, K.V., “Environmentally-benign transition metal catalyst design using optimization techniques”, Comput. Chem. Eng., 28(5), 605-611(2004).
25 Fredenslund, A., Jones, R.L., Prausnitz, J.M., ”Group-Contribution estimation of activity coefficients in non ideal liquid mixtures”, AIChE J., 21(6), 1086-1099(1975).
26 Joback, K.G., Reid, R.C., “Estimation of pure component properties from group contributions”, Chem. Eng. Comm., 57, 233-237(1987).
27 Constantinou, L., Gani, R., “New Group-contribution method for estimating properties of pure compounds”, AIChE J., 40(10), 1697-1710(1994).
28 Marrero, J., Gani, R., “Group contribution based estimation of pure component properties”, Fluid phase Equilib., 183/184, 183-208(2001).
29 Kang, J.W., Abildskov, J., Gani, R., Cobas, J., “Estimation of mixture properties from first and second-order group contributions with the UNIFAC model”, Ind. Eng. Chem. Res., 41(13), 3260-3273(2002).
30 Brignole, E.A., Bottini, S., Gani, R., “A strategy for the design of solvents for separation processes”, Fluid Phase Equilib., 29, 125-132(1986).
31 Gani, R., Neilsen, B., Fredenslund, A., “Group contribution approach to computer aided molecular design”, AIChE J., 37, 1318-1332(1991).
32 Marcoulaki, E.C., Kokossis, A.C., “On the development of novel chemicals using systematic optimization approach. Part I. Optimization framework”, Chem. Eng. Sci., 55(13), 2529-2546(2000).
33 Harper, P.M., Gani, R., Kolar, P., Ishikawa, T., “Computer-aided molecular design with combined molecular modeling and group contribution”, Fluid Phase Equilib., 158/160, 337-347(1999).
34 Frank, T.C., Downey, J.R., Gupta, S.K., “Quickly screen solvents for organic solids”, Chem. Eng. Prog., 95(12), 41-61(1999).
35 ICAS, “Documentation”, CAPEC, Department of Chemical Engineering, Technical University of Denmark(2003).
36 Martin, T.M., Young, D.M., “Prediction of the acute toxicity(96-h LC 50 ) of organic compounds to the fathead minnow(Pimephales promelas) using group contribution method”, Chem. Res. Toxicol., 14, 1378-1385(2001).
37 Garekani, H.A., Sadeghi, F., Badiee, A., Mostafa, S.A., Rajabi-Siahboomi, A.R., “Crystal habit modifications of ibuprofen and their physicochemical characteristics”, Drug Dev. Ind. Pharm., 27(8), 803-809(2001).

[1]	Xia Miao, Xiaofan Pang, Shiyu Li, Haoguang Wei, Jianhao Yin, Xiangming Kong. Mechanical strength and the degradation mechanism of metakaolin based geopolymer mixed with ordinary Portland cement and cured at high temperature and high relative humidity[J]. 中国化学工程学报, 2023, 60(8): 118-130.
[2]	Yingxi Gao, Jiayi Shi, Jie Wang, Fan Zhang, Shichao Tian, Zhiyong Zhou, Zhongqi Ren. Enrichment of nervonic acid in Acer truncatum Bunge oil by combination of two-stage molecular distillation, one-stage urea complexation and five-stage solvent crystallization[J]. 中国化学工程学报, 2023, 59(7): 61-71.
[3]	Guangyuan Chen, Tong Zhou, Meng Zhang, Zhongxiang Ding, Zhikun Zhou, Yuanhui Ji, Haiying Tang, Changsong Wang. Effects of heavy metal ions Cu²⁺/Pb²⁺/Zn²⁺ on kinetic rate constants of struvite crystallization[J]. 中国化学工程学报, 2023, 57(5): 10-16.
[4]	Pengbao Lian, Lizhen Chen, Dan He, Guangyuan Zhang, Zishuai Xu, Jianlong Wang. Crystallization thermodynamics of 2,4(5)-dinitroimidazole in binary solvents[J]. 中国化学工程学报, 2023, 57(5): 173-182.
[5]	Qiaoqiao Liu, Guihong Lin, Jian Zhou, Liangliang Huang, Chang Liu. Hydrogen-bond mediated and concentrate-dependent NaHCO₃ crystal morphology in NaHCO₃–Na₂CO₃ aqueous solution: Experiments and computer simulations[J]. 中国化学工程学报, 2023, 55(3): 49-58.
[6]	Dandan Ren, Shanshan Xiang, Yuwen Yan, Ruiying Kong, Xingchu Gong. Design and optimization of purification process of sinomenine hydrochloride[J]. 中国化学工程学报, 2023, 55(3): 63-72.
[7]	Zhengchi Yin, Xiaoke Wu, Yanwei Yang, Huayu Zhang, Wangtao Li, Ruimin Zhu, Qiancheng Zheng, Zhengbao Wang. Fabrication of ZIF-8 membranes on dual-layer ZnO-PES/PES organic hollow fibers by in-situ crystallization[J]. 中国化学工程学报, 2023, 55(3): 101-110.
[8]	Meng Li, Jianliang Xu, Huixia Xiao, Xia Liu, Guangsuo Yu, Xueli Chen. Exploring influence of MgO/CaO on crystallization characteristics to understand fluidity of synthetic coal slags[J]. 中国化学工程学报, 2023, 53(1): 1-13.
[9]	Fang Chen, Tao Zhou, Lijie Li, Chongwei An, Jun Li, Duanlin Cao, Jianlong Wang. Morphology prediction of dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50) crystal in different solvent systems using modified attachment energy model[J]. 中国化学工程学报, 2023, 53(1): 181-193.
[10]	Pengbao Lian, Lizhen Chen, Daozhen Huang, Jianxin Xu, Zishuai Xu, Cai Cao, Jiaxiang Zhao, Jianlong Wang. Crystallization thermodynamics of 2,4(5)-dinitroimidazole in eleven pure solvents[J]. 中国化学工程学报, 2022, 48(8): 236-243.
[11]	Jialu Zhang, Xiang Liu, Shuai Liu, Yuxing Li, Qihui Hu, Wuchang Wang. Microscopic morphology evolution of the crystal structure of tetrahydrofuran hydrate under flowing condition[J]. 中国化学工程学报, 2022, 45(5): 103-110.
[12]	Yuanjie Li, Qiuxiang Yin, Meijing Zhang, Ying Bao, Baohong Hou, Jingkang Wang, Jiting Huang, Ling Zhou. Characterization and structure analysis of the heterosolvate of erythromycin thiocyanate[J]. 中国化学工程学报, 2022, 44(4): 268-274.
[13]	Xin Jiang, Baojiang Sun, Zhiyuan Wang, Wantian Zhou, Jiakai Ji, Litao Chen. Methane hydrate crystal growth on shell substrate[J]. 中国化学工程学报, 2022, 43(3): 50-61.
[14]	Zhaofeng Zhang, Juanjuan Ding, Min Wu, Bochao Liu, Huiwen Song, Shengping You, Wei Qi, Rongxin Su, Zhimin He. Development of an integrated process for the production of high-purity γ-aminobutyric acid from fermentation broth[J]. 中国化学工程学报, 2022, 50(10): 361-368.
[15]	Xiaobin Liu, Zhenguo Gao, Jingcai Cheng, Junbo Gong, Jingkang Wang. Research progress on preparation and purification of fluorine-containing chemicals in lithium-ion batteries[J]. 中国化学工程学报, 2022, 41(1): 73-84.