Citation: Shifang Song, Chenyu Wu, Li Zhang, Dezhi Yang, Yang Lu, Zhengzheng Zhou. Unpacking phase transitions in multi-component drug systems: A case study[J]. Chinese Chemical Letters, ;2025, 36(7): 110911. doi: 10.1016/j.cclet.2025.110911 shu

Unpacking phase transitions in multi-component drug systems: A case study

Shifang Song ^a ,
Chenyu Wu ^a ,
Li Zhang ^b ,
Dezhi Yang ^{b, *,} ,
Yang Lu ^b ,
Zhengzheng Zhou ^{a, *,}

a.
NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Hygiene Inspection & Quarantine Science, School of Public Health, Southern Medical University, Guangzhou 510515, China
b.
Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

ydz@imm.ac.cn

zhouzz418@smu.edu.cn

Received Date: 16 December 2024
Revised Date: 24 January 2025
Accepted Date: 3 February 2025
Available Online: 4 February 2025

Figures(4)

The phase transition among different solid forms of active pharmaceutical ingredients can significantly influence their physicochemical properties, potentially leading to clinical safety risks. However, phase transition mechanisms remain under explored, especially in multi-component drugs. Here we report a novel ciprofloxacin-diclofenac salt system and investigate phase transitions among its anhydrate, dihydrate, and methanol solvate forms. The study focused on the influence of water activity and solvent vapor conditions, elucidating the role of guest molecules in driving these transitions. These findings offer new insights into polymorphic phase transitions, advancing our understanding of stability and performance in pharmaceutical formulations.
- Phase transition,
- Water activity,
- Solvent vapor,
- Ciprofloxacin,
- Diclofenac
1. [1]
  D. Singhal, Adv. Drug Deliv. Rev. 56 (2004) 335–347.
2. [2]
  Z. Zhou, M. Calatayud, J. Contreras-Garcia, et al., J. Pharm. Sci. 108 (2019) 3340–3347.
3. [3]
  H. Wang, D, Yang, W. Zhang, et al., Chin. Chem. Lett. 34 (2023) 107258. doi: 10.1016/j.cclet.2022.02.063
4. [4]
  H. Liu, H.S. Chan, L. Zhang, et al., Chin. Chem. Lett. 34 (2023) 108057. doi: 10.1016/j.cclet.2022.108057
5. [5]
  L. Lange, G. Sadowski, Cryst. Growth Des. 16 (2016) 4439–4449. doi: 10.1021/acs.cgd.6b00554
6. [6]
  K.K. Arora, S. Thakral, R. Suryanarayanan, Pharm. Res. 30 (2013) 1779–1789. doi: 10.1007/s11095-013-1022-7
7. [7]
  I. Sathisaran, S.V. Dalvi, Cryst. Growth Des. 21 (2021) 2076–2092. doi: 10.1021/acs.cgd.0c01513
8. [8]
  Z. Zhou, H.H. Tong, L. Li, et al., Cryst. Res. Technol. 50 (2015) 538–548. doi: 10.1002/crat.201500034
9. [9]
  Z.Y. Fang, B.X. Zhang, W.H. Xing, Chin. Chem. Lett. 33 (2022) 2159–2164. doi: 10.1016/j.cclet.2021.10.056
10. [10]
  A. Joseph, C.E. Bernardes, A.I. Druzhinina, et al., Cryst. Growth Des. 17 (2017) 1918–1932. doi: 10.1021/acs.cgd.6b01876
11. [11]
  L. Ma, Q. Zheng, D.K. Unruh, Chem. Commun. 10 (2023) 3640–3654.
12. [12]
  J.H. Horst, P.W. Cains, Cryst. Growth Des. 8 (2008) 2537–2542. doi: 10.1021/cg800183v
13. [13]
  K.M. Lutker, R. Quiñones, J. Xu, A. Ramamoorthy, A.J. Matzger, J. Pharm. Sci. 100 (2011) 949–963. doi: 10.1002/jps.22336
14. [14]
  S. Karki, T. Friščić, W. Jones, W.S. Motherwell, Mol. Pharmaceut. 4 (2007) 347–354. doi: 10.1021/mp0700054
15. [15]
  P. Sanphui, S.S. Kumar, A. Nangia, Cryst. Growth Des. 12 (2012) 4588–4599. doi: 10.1021/cg300784v
16. [16]
  Z. Li, J. Zhou, X. Zhang, S. Wu, J. Gong, Chin. Chem. Lett. 34 (2023) 107983. doi: 10.1016/j.cclet.2022.107983
17. [17]
  P. Yang, C. Qin, S. Du, et al., Crystals 9 (2019) 367. doi: 10.3390/cryst9070367
18. [18]
  D. Rossi, T. Gelbrich, V. Kahlenberg, U.J. Griesser, CrystEngComm 14 (2012) 2494–2506. doi: 10.1039/c2ce06659a
19. [19]
  S. Aitipamula, P.S. Chow, R.B. Tan, CrystEngComm 14 (2012) 691–699.
20. [20]
  S. Majodina, L. Ndima, O.O. Abosede, et al., CrystEngComm 23 (2021) 335–352. doi: 10.1039/d0ce01387k
21. [21]
  X.B. Zhou, J.R. Zhu, J.M. Gu, X.R. Hu, Acta Crystallogr., Sect. C: Struct. Chem. 74 (2018) 690–695. doi: 10.1107/s2053229618006836
22. [22]
  J. Yang, C.T. Hu, A.G. Shtukenberg, et al., CrystEngComm 20 (2018) 1383–1389. doi: 10.1039/c7ce02107k
23. [23]
  H. Liu, J. Nie, H.S. Chan, et al., Int. J. Pharmacuet. 601 (2021) 120537.
24. [24]
  Z. Li, H. Qu, L. Fang, S. Wu, J. Gong, Chin. Chem. Lett. 34 (2023) 107504. doi: 10.1016/j.cclet.2022.05.018
25. [25]
  S.K. Rai, S. Allu, A.K. Nangia, Cryst. Growth Des. 20 (2020) 4512–4522. doi: 10.1021/acs.cgd.0c00313
26. [26]
  N. Qiao, K. Wang, W. Schlindwein, A. Davies, M. Li, Eur. J. Pharm. Biopharm. 83 (2013) 415–426.
27. [27]
  M. Omori, T. Uekusa, J. Oki, D. Inoue, K. Sugano, J. Drug Deliv. Sci. Technol. 56 (2020) 101566.
28. [28]
  D. Huang, D. Yang, Y. Lv, et al., J. Mol. Struct. 1250 (2022) 131891.
29. [29]
  Y. Li, P.S. Chow, R.B. Tan, Int. J. Pharmaceut. 415 (2011) 110–118.
30. [30]
  J. Li, Y. Huang, Q. An, et al., Int. J. Pharmaceut. 628 (2022) 122310.
31. [31]
  M.M.H. Smets, S.J.T. Brugman, E.R.H. Van Eck, et al., Cryst. Growth Des. 15 (2015) 5157–5167. doi: 10.1021/acs.cgd.5b01188
32. [32]
  M.C. Meyer, A.B. Straughn, E.J. Jarvi, et al., Pharm. Res. 9 (1992) 1612–1616.
33. [33]
  D. Murphy, F. Rodrıguez-Cintrón, B. Langevin, et al., Int. J. Pharmaceut. 246 (2002) 121–134.
34. [34]
  J. Bauer, S. Spanton, R. Henry, et al., Pharm. Res. 18 (2001) 859–866.
35. [35]
  N. Zencirci, T. Gelbrich, D.C. Apperley, et al., Cryst. Growth Des. 10 (2010) 302–313. doi: 10.1021/cg901062n
36. [36]
  Y. Liu, A. Li, S. Xu, et al., Angew. Chem. Int. Ed. 59 (2020) 15098–15103. doi: 10.1002/anie.202002220
37. [37]
  F. Van Bambeke, J.M. Michot, J. Van Eldere, P.M. Tulkens, Clin. Microbiol. Infect. 11 (2005) 256–280. doi: 10.1111/j.1469-0691.2005.01131.x
38. [38]
  G. Liu, J. Liu, Y. Liu, et al., J. Am. Chem. Soc. 136 (2014) 590–593. doi: 10.1021/ja4102634
39. [39]
  A. Karagianni, M. Malamatari, K. Kachrimanis, Pharmaceutics 10 (2018) 18. doi: 10.3390/pharmaceutics10010018
40. [40]
  H. Liu, H.H.Y. Tong, Z. Zhou, J. Therm. Anal. Calorim. 147 (2022) 12947–12963. doi: 10.1007/s10973-022-11762-1
41. [41]
  C.B. Romañuk, Y.G. Linck, A.K. Chattah, et al., Int. J. Pharmaceut. 391 (2010) 197–202.
42. [42]
  D.M. Campoli-Richards, J.P. Monk, A. Price, et al., Drugs 35 (1988) 373–447. doi: 10.2165/00003495-198835040-00003
43. [43]
  T.J. Gan, Curr. Med. Res. Opin. 26 (2010) 1715–1731. doi: 10.1185/03007995.2010.486301
44. [44]
  G.G. Zhang, D. Law, E.A. Schmitt, et al., Adv. Drug Deliv. Rev. 56 (2004) 371–390.
45. [45]
  H. Wang, L. Wang, G. Xie, et al., Cryst. Growth Des. 24 (2024) 3399–3409. doi: 10.1021/acs.cgd.4c00120
46. [46]
  A.O. Surov, A.P. Voronin, A.N. Manin, et al., Mol. Pharmaceut. 11 (2014) 3707–3715. doi: 10.1021/mp5004652
47. [47]
  T.S. Thakur, R. Thakuria, Cryst. Growth Des. 20 (2020) 6245–6265. doi: 10.1021/acs.cgd.0c00654
48. [48]
  L. Yuan, E. Horosanskaia, F. Engelhardt, et al., Cryst. Growth Des. 19 (2019) 854–867. doi: 10.1021/acs.cgd.8b01425
49. [49]
  S. Rajabnezhad, T. Ghafourian, A. Rajabi-Siahboomi, et al., Carbohydr. Polym. 238 (2020) 116208.
50. [50]
  K. Greco, R. Bogner, J. Pharm. Sci. 101 (2012) 2996–3018. doi: 10.1002/jps.23025
51. [51]
  H. Wikström, J. Rantanen, A.D. Gift, L.S. Taylor, Cryst. Growth Des. 8 (2008) 2684–2693. doi: 10.1021/cg070629e
52. [52]
  R.J. Davey, N. Blagden, S. Righini, H. Alison, E.S. Ferrari, J. Phys. Chem. B 106 (2002) 1954–1959.
53. [53]
  E. Arunan, G.R. Desiraju, R.A. Klein, et al., Pure Appl. Chem. 83 (2011) 1637–1641. doi: 10.1351/pac-rec-10-01-02
54. [54]
  J. Weng, Y. Huang, D. Hao, Y. Ji, Chin. J. Chem. Eng. 28 (2020) 935–948.
55. [55]
  L. Jia, M. Guo, J. Dai, et al., Cryst. Growth Des. 23 (2023) 832–841. doi: 10.1021/acs.cgd.2c01071
56. [56]
  A. Berzins, D. Zvanina, A. Trimdale, Cryst. Growth Des. 18 (2018) 2040–2045. doi: 10.1021/acs.cgd.7b01457
57. [57]
  S. Emamian, T. Lu, H. Kruse, H. Emamian, J. Comput. Chem. 40 (2019) 2868–2881. doi: 10.1002/jcc.26068
58. [58]
  D. Yang, H. Wang, Q. Liu, et al., Chin. Chem. Lett. 33 (2022) 3207–3211. doi: 10.1016/j.cclet.2021.10.012
59. [59]
  F. Li, Z. Zheng, S. Xia, L. Yu, J. Mol. Struct. 1219 (2020) 128480.
60. [60]
  A.J. Aquino, D. Tunega, G. Haberhauer, M.H. Gerzabek, H. Lischka, J. Phys. Chem. A 106 (2002) 1862–1871. doi: 10.1021/jp013677x
61. [61]
  V.A. Russell, M.D. Ward, Chem. Mater. 8 (1996) 1654–1666.
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