Preparation and Characterization of Two Polymorphs of (3aRS,4RS,7RS,7aSR)-2-(Tricyclo[3.3.1.13,7]decan-1-yl)-4,5,6,7-tetrahydro-4,7-eposyisoindoline-1,3-dione (SU2162) with PXRD and DSC
Author(s)
Wenfei Chen,
Zaiyou Tan*,
Lin Luo,
Ruisi Yan,
Hui Yang,
Chunmei Tong,
Yuqing Huang,
Tingyu Huang,
Yang Yang,
Ruonan Wang
ABSTRACT
Objective: To develop the characterization of the polymorphs and the best preparation method of two forms of the title compound (SU2162). After SU2162 was prepared in accordance with the patent process, the crystal form I was recrystallized by ethyl acetate and the crystal form II was obtained by the recrystal in acetone. And the two crystal forms were characterized with differential scanning calorimetry (DSC) and X-ray powder diffraction (PXRD). The melting point of crystal form I (triclinic) is at 158°C, and the melting point of crystal form II (monoclinic) is at 163°C. The PXRD studies of the two crystalline samples indicate that they have the distinct diffraction patterns. The method herein can be stably prepared for the two crystal forms of the title compound.
Objective: To develop the characterization of the polymorphs and the best preparation method of two forms of the title compound (SU2162). After SU2162 was prepared in accordance with the patent process, the crystal form I was recrystallized by ethyl acetate and the crystal form II was obtained by the recrystal in acetone. And the two crystal forms were characterized with differential scanning calorimetry (DSC) and X-ray powder diffraction (PXRD). The melting point of crystal form I (triclinic) is at 158°C, and the melting point of crystal form II (monoclinic) is at 163°C. The PXRD studies of the two crystalline samples indicate that they have the distinct diffraction patterns. The method herein can be stably prepared for the two crystal forms of the title compound.
Cite this paper
Chen, W. , Tan, Z. , Luo, L. , Yan, R. , Yang, H. , Tong, C. , Huang, Y. , Huang, T. , Yang, Y. and Wang, R. (2015) Preparation and Characterization of Two Polymorphs of (3aRS,4RS,7RS,7aSR)-2-(Tricyclo[3.3.1.13,7]decan-1-yl)-4,5,6,7-tetrahydro-4,7-eposyisoindoline-1,3-dione (SU2162) with PXRD and DSC. Advances in Materials Physics and Chemistry, 5, 16-21. doi: 10.4236/ampc.2015.51003.
Chen, W. , Tan, Z. , Luo, L. , Yan, R. , Yang, H. , Tong, C. , Huang, Y. , Huang, T. , Yang, Y. and Wang, R. (2015) Preparation and Characterization of Two Polymorphs of (3aRS,4RS,7RS,7aSR)-2-(Tricyclo[3.3.1.13,7]decan-1-yl)-4,5,6,7-tetrahydro-4,7-eposyisoindoline-1,3-dione (SU2162) with PXRD and DSC. Advances in Materials Physics and Chemistry, 5, 16-21. doi: 10.4236/ampc.2015.51003.
References
[1] American Cancer Society (2014) Cancer Facts & Figures 2014. American Cancer Society, Atlanta.
http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2014/index [2] Stewart, B.W. and Wild, C.P. (2014) World Cancer Report 2014. International Agency for Research on Cancer, France.
http://www.esmo.org/Oncology-News/World-Cancer-Report-2014 [3] O’Callaghan, T. (2011) Introduction: The Prevention Agenda. Nature, 471, S2-S4.
http://www.nature.com/nature/journal/v471/n7339_supp/fig_tab/471S2a_F1.html
http://dx.doi.org/10.1038/471S2a [4] Tan, Z. (2008) Chinese Patent No. 2007100297361. [5] Tan, Z., Luo, L., Zhu, E., Yan, R. and Lin, Z. (2010) (3aRS,4SR,7RS,7aSR)-2-(Tricyclo-[3.3.1.1]decan-1-yl)-4,5,6,7- tet-ra-hydro-4,7-epoxyisoindoline-1,3-dione. Acta Crystallographica Section E, 66, Article ID: o1374.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2979399/
http://dx.doi.org/10.1107/S1600536810016971 [6] Tan, Z.Y., Luo, L., Zhu, E.J., Lin, Z.H., Yan, R.S., Zhang, H. and Liang, K. (2010) Preparation and X-Ray Diffraction Analysis of a New Crystal Form of (3aRS,4RS,7RS,7aSR)-2-(Tricyclo[3.3.1.13,7]decan-1-yl)-4,5,6,7-tetrahydro-4,7-epoxyisoin-doline-1,3-dione—A Novel Anticancer Compound. Journal of Guangdong Pharmaceutical College, 26, 441-444.
http://www.cqvip.com/QK/90465A/201006/37126978.html [7] Tan, Z.Y., Yan, R.S., Lu, J.H., Ye, Q., Guan, W.S., Zhang, X.L. and Yang, H. (2012) Determination of (3aRS,4SR, 7RS,7aSR)-2-(Tricyclo-[3.3.1.13,7]decan-1-yl)-4,5,6,7-tetrahydro-4,7-epoxyisoindoline-1,3-dione (SU2162) in Rat Plasma by High-Performance Liquid Chromatography with UV Detection. The Analytical Chemistry, 11, 347-352. [8] Tan, Z., Yang, H., Yan, R., Liu, R., Li, X., Ye, Q., Guan, W., Zhang, X., Huang, Y., Tong, C. and Chen, W. (2014) Pharmacokinetics and Tissue Distribution of SU2162, a Novel Anticancer Drug, after Intravenous Administration in Rats. Journal of Pharmaceutical Technology and Drug Research, 3, 1-6.
http://www.hoajonline.com/jptdr/2050-120X/3/1
http://dx.doi.org/10.7243/2050-120X-3-1 [9] Huang, Y.Q., Tan, Z.Y., Luo, L., Yang, H., Tong, C.M., Chen, W.F., Huang, T.Y. and Liu, R.L. (2014) The Polymorphism and Transformation of (3aRS,4RS,7RS,7aSR)-2-(Tricyclo[3.3.1.13,7]decan-1-yl)-4,5,6,7-tetrahydro-4,7-eposyi-soindoline-1,3-dione (SU2162)—A Novel Anticancer Compound. Journal of Crystallization Process and Technology, 4, 27-30.
http://dx.doi.org/10.4236/jcpt.2014.41004 [10] Sinko, P.J. (2006) Martin’s Physical Pharmacy and Pharmaceutical Sciences. 5th Edition, Lippincott Williams & Wilkins, Philadelphia. [11] Brittain, H.G. (1995) Physical Characterization of Pharmaceutical Solid. Vol. 70, Marcel Dekker, New York.
http://dx.doi.org/10.1201/b14204
[1] American Cancer Society (2014) Cancer Facts & Figures 2014. American Cancer Society, Atlanta.
http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2014/index [2] Stewart, B.W. and Wild, C.P. (2014) World Cancer Report 2014. International Agency for Research on Cancer, France.
http://www.esmo.org/Oncology-News/World-Cancer-Report-2014 [3] O’Callaghan, T. (2011) Introduction: The Prevention Agenda. Nature, 471, S2-S4.
http://www.nature.com/nature/journal/v471/n7339_supp/fig_tab/471S2a_F1.html
http://dx.doi.org/10.1038/471S2a [4] Tan, Z. (2008) Chinese Patent No. 2007100297361. [5] Tan, Z., Luo, L., Zhu, E., Yan, R. and Lin, Z. (2010) (3aRS,4SR,7RS,7aSR)-2-(Tricyclo-[3.3.1.1]decan-1-yl)-4,5,6,7- tet-ra-hydro-4,7-epoxyisoindoline-1,3-dione. Acta Crystallographica Section E, 66, Article ID: o1374.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2979399/
http://dx.doi.org/10.1107/S1600536810016971 [6] Tan, Z.Y., Luo, L., Zhu, E.J., Lin, Z.H., Yan, R.S., Zhang, H. and Liang, K. (2010) Preparation and X-Ray Diffraction Analysis of a New Crystal Form of (3aRS,4RS,7RS,7aSR)-2-(Tricyclo[3.3.1.13,7]decan-1-yl)-4,5,6,7-tetrahydro-4,7-epoxyisoin-doline-1,3-dione—A Novel Anticancer Compound. Journal of Guangdong Pharmaceutical College, 26, 441-444.
http://www.cqvip.com/QK/90465A/201006/37126978.html [7] Tan, Z.Y., Yan, R.S., Lu, J.H., Ye, Q., Guan, W.S., Zhang, X.L. and Yang, H. (2012) Determination of (3aRS,4SR, 7RS,7aSR)-2-(Tricyclo-[3.3.1.13,7]decan-1-yl)-4,5,6,7-tetrahydro-4,7-epoxyisoindoline-1,3-dione (SU2162) in Rat Plasma by High-Performance Liquid Chromatography with UV Detection. The Analytical Chemistry, 11, 347-352. [8] Tan, Z., Yang, H., Yan, R., Liu, R., Li, X., Ye, Q., Guan, W., Zhang, X., Huang, Y., Tong, C. and Chen, W. (2014) Pharmacokinetics and Tissue Distribution of SU2162, a Novel Anticancer Drug, after Intravenous Administration in Rats. Journal of Pharmaceutical Technology and Drug Research, 3, 1-6.
http://www.hoajonline.com/jptdr/2050-120X/3/1
http://dx.doi.org/10.7243/2050-120X-3-1 [9] Huang, Y.Q., Tan, Z.Y., Luo, L., Yang, H., Tong, C.M., Chen, W.F., Huang, T.Y. and Liu, R.L. (2014) The Polymorphism and Transformation of (3aRS,4RS,7RS,7aSR)-2-(Tricyclo[3.3.1.13,7]decan-1-yl)-4,5,6,7-tetrahydro-4,7-eposyi-soindoline-1,3-dione (SU2162)—A Novel Anticancer Compound. Journal of Crystallization Process and Technology, 4, 27-30.
http://dx.doi.org/10.4236/jcpt.2014.41004 [10] Sinko, P.J. (2006) Martin’s Physical Pharmacy and Pharmaceutical Sciences. 5th Edition, Lippincott Williams & Wilkins, Philadelphia. [11] Brittain, H.G. (1995) Physical Characterization of Pharmaceutical Solid. Vol. 70, Marcel Dekker, New York.
http://dx.doi.org/10.1201/b14204