Skip to main content
Log in

Solvates and polymorphs of clindamycin phosphate: Structural, thermal stability and moisture stability studies

  • Research Article
  • Published:
Frontiers of Chemical Science and Engineering Aims and scope Submit manuscript

Abstract

Clindamycin phosphate (CP), an antibacterial agent, has been reported to form several solid-state forms. The crystal structures of two CP solvates, a dimethyl sulfoxide (DMSO) solvate and a methanol/water solvate (solvate V), have been determined by single crystal X-ray diffraction. The properties and transformations of these forms were characterized by powder X-ray diffraction, Single-crystal X-ray diffraction, differential scanning calorimetry, thermo gravimetric analysis, hot-stage microscopy, and dynamic vapor sorption. Very different hydrogen bonding networks exist among the host-host and host-solvent molecules in the two crystal structures, resulting in different moisture stabilities. The thermal stabilities of the two solvates upon heating and desolvation were also studied. When the temperature was above the boiling point of methanol, solvate V converted to a polymorphic phase after a one step desolvation process, whereas the desolvation temperature of the DMSO solvate was below the boiling point of DMSO. At the relative humidity above 43%, the DMSO solvate transformed to a hydrate at 25 °C. In contrast, solvate V did not transform at any of the humidities studied.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Fujii K, Aoki M, Uekusa H. Solid-state hydration/dehydration of erythromycin A investigated by ab initio powder X-ray diffraction analysis: Stoichiometric and nonstoichiometric dehydrated hydrate. Crystal Growth & Design, 2013, 13(5): 2060–2066

    Article  CAS  Google Scholar 

  2. Cui P, Yin Q, Guo Y, Gong J. Polymorphic crystallization and transformation of candesartan cilexetil. Industrial & Engineering Chemistry Research, 2012, 51(39): 12910–12916

    Article  CAS  Google Scholar 

  3. Fujii K, Uekusa H, Itoda N, Yonemochi E, Terada K. Mechanism of dehydration-hydration processes of lisinopril dihydrate investigated by ab initio powder X-ray diffraction analysis. Crystal Growth & Design, 2012, 12(12): 6165–6172

    Article  CAS  Google Scholar 

  4. Gillon A L, Davey R J, Storey R, Feeder N, Nichols G, Dent G, Apperley D C. Solid state dehydration processes: Mechanism of water loss from crystalline inosine dihydrate. Journal of Physical Chemistry B, 2005, 109(11): 5341–5347

    Article  CAS  Google Scholar 

  5. Chakravarty P, Suryanarayanan R. Characterization and structure analysis of thiamine hydrochloride methanol solvate. Crystal Growth & Design, 2010, 10(10): 4414–4420

    Article  CAS  Google Scholar 

  6. Renou L, Coste S, Cartigny Y, Petit M, Vincent C, Schneider J M, Coquerel G. Mechanism of hydration and dehydration of ciclopirox ethanolamine (1:1). Crystal Growth & Design, 2009, 9(9): 3918–3927

    Article  CAS  Google Scholar 

  7. Jing D, Wang Y, Chen Z, Zhou L, Wang J. Polymorphism and crystal transformation of penicillin sulfoxide. Frontiers of Chemical Science and Engineering, 2011, 5(4): 442–447

    Article  CAS  Google Scholar 

  8. Rohani S. Applications of the crystallization process in the pharmaceutical industry. Frontiers of Chemical Engineering in China, 2010, 4(1): 2–9

    Article  CAS  Google Scholar 

  9. Lu J, Li Z, Jiang X. Polymorphism of pharmaceutical molecules: Perspectives on nucleation. Frontiers of Chemical Engineering in China, 2010, 4(1): 37–44

    Article  CAS  Google Scholar 

  10. Zhang X, Yin Q, Du W, Gong J, Bao Y, Zhang M, Hou B, Hao H. Phase transformation between anhydrate and monohydrate of sodium dehydroacetate. Industrial & Engineering Chemistry Research, 2015, 54(13): 3438–3444

    Article  CAS  Google Scholar 

  11. Jali B R, Baruah J B. Polymorphs and solvates of 2-(1,4-dihydro-1,4-dioxonaphthalen-3-ylthio)benzoic acid. Crystal Growth & Design, 2012, 12(6): 3114–3122

    Article  CAS  Google Scholar 

  12. Zimmermann A, Frøstrup B, Bond A D. Polymorphs of pridopidine hydrochloride. Crystal Growth & Design, 2012, 12(6): 2961–2968

    Article  CAS  Google Scholar 

  13. Shevchenko A, Belle D D, Tiittanen S, Karjalainen A, Tolvanen A, Tanninen V P, Haarala J, Mäkelä M, Yliruusi J, Miroshnyk I. Coupling polymorphism/Solvatomorphism and physical stability evaluation with early salt synthesis optimization of an investigational drug. Organic Process Research & Development, 2011, 15(3): 666–672

    Article  CAS  Google Scholar 

  14. Aitipamula S, Chow P S, Tan R B H. Solvates and polymorphic phase transformations of 2-chloro-4-nitrobenzoic acid. CrystEng-Comm, 2011, 13(3): 1037–1045

    Article  CAS  Google Scholar 

  15. Braun D E, Gelbrich T, Kahlenberg V, Tessadri R, Wieser J, Griesser U J. Stability of solvates and packing systematics of nine crystal forms of the antipsychotic drug aripiprazole. Crystal Growth & Design, 2009, 9(2): 1054–1065

    Article  CAS  Google Scholar 

  16. Bisht K K, Kathalikkattil A C, Suresh E. Hydrogen-bonded one-and two-dimensional hybrid water-chloride motifs. Crystal Growth & Design, 2012, 12(2): 556–561

    Article  CAS  Google Scholar 

  17. Jungwirth P, Tobias D J. Ions at the air/water interface. Journal of Physical Chemistry B, 2002, 106(25): 6361–6373

    Article  CAS  Google Scholar 

  18. Hossain M A, Saeed M A, Fronczek F R, Wong B M, Dey K R, Mendy J S, Gibson D. Charge-assisted encapsulation of two chlorides by a hexaprotonated azamacrocycle. Crystal Growth & Design, 2010, 10(4): 1478–1481

    Article  CAS  Google Scholar 

  19. Vippagunta S R, Brittain H G, Grant D J W. Crystalline solids. Advanced Drug Delivery Reviews, 2001, 48(1): 3–26

    Article  CAS  PubMed  Google Scholar 

  20. Bakhoda A, Khavasi H R, Safari N. Discrete cubane-like bromidewater cluster. Crystal Growth & Design, 2011, 11(4): 933–935

    Article  CAS  Google Scholar 

  21. Matsuo K, Matsuoka M. Solid-state polymorphic transition of theophylline anhydrate and humidity effect. Crystal Growth & Design, 2007, 7(2): 411–415

    Article  CAS  Google Scholar 

  22. Singh D, Baruah J B. Structural study on solvates of dopaminebased cyclic imide derivatives. Crystal Growth & Design, 2011, 11(3): 768–777

    Article  CAS  Google Scholar 

  23. Morris K R, Griesser U J, Eckhardt C J, Stowell J G. Theoretical approaches to physical transformations of active pharmaceutical ingredients during manufacturing processes. Advanced Drug Delivery Reviews, 2001, 48(1): 91–114

    Article  CAS  PubMed  Google Scholar 

  24. Babu N J, Nangia A. Multiple Z′ in carboxylic acid-pyridine trimer synthon and Kagomé lattice in the structure of 5-methylpyrazine-2,3-dicarboxylic acid. Crystal Growth & Design, 2006, 6(9): 1995–1999

    Article  CAS  Google Scholar 

  25. Bhattacharya S, Sameena J, Saha B K. Solvates of ajmaline and twodimensional isostructurality between methanol and ethanol solvates. Crystal Growth & Design, 2011, 11(4): 905–909

    Article  CAS  Google Scholar 

  26. Liu Z, Yin Q, Zhang X, Gong J, Xie C. Characterization and structure analysis of cefodizime sodium solvates crystallized from water and ethanol binary solvent mixtures. Industrial & Engineering Chemistry Research, 2014, 53(8): 3373–3377

    Article  CAS  Google Scholar 

  27. Stevens D L, Maier K A, Laine B M, Mitten J E. Comparison of clindamycin, rifampin, tetracycline, metronidazole, and penicillin for efficacy in prevention of experimental gas gangrene due to Clostridium perfringens. Journal of Infectious Diseases, 1987, 155(2): 220–228

    Article  CAS  PubMed  Google Scholar 

  28. Ran Y, Dong W, Wu S, Wang J, Gong J. Transformations among the new solid-state forms of clindamycin phosphate. Organic Process Research & Development, 2013, 17(11): 1445–1450

    Article  CAS  Google Scholar 

  29. ASTM. Standard Practice for Maintaining Constant Relative Humidity by Means of Aqueous Glycerin Solutions. ASTM E104-85, 1996

    Google Scholar 

  30. Nyqvist H, Nyqvist H. Saturated salt solutions for maintaining specified relative humidity. Energy, 1980, 10: 1085–1090

    Google Scholar 

  31. Fujii K, Ashida Y, Uekusa H, Hirano S, Toyota S, Toda F, Pan Z, Harris K D M. Vapour induced crystalline transformation investigated by ab initio powder X-ray diffraction analysis. Crystal Growth & Design, 2009, 9(2): 1201–1207

    Article  CAS  Google Scholar 

  32. Chavez K J, Guevara M, Rousseau R W. Characterization of solvates formed by sodium naproxen and an homologous series of alcohols. Crystal Growth & Design, 2010, 10(8): 3372–3377

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful for the financial support from the National Natural Science Foundation of China (Grant Nos. 81361140344 and 2136164), the National High Technology Research and Development Program of China (2015AA021002) and the Major National Scientific Instrument Development Project (No.21537812).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Junbo Gong.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gong, J., Zhang, D., Ran, Y. et al. Solvates and polymorphs of clindamycin phosphate: Structural, thermal stability and moisture stability studies. Front. Chem. Sci. Eng. 11, 220–230 (2017). https://doi.org/10.1007/s11705-017-1624-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11705-017-1624-4

Keywords

Navigation