Skip to main content
SpringerLink
Log in

General Trends in the Desolvation Behavior of Calcium Salts

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

This paper is concerned with the solid-state characterization of dehydrated calcium salts as well as the effect of dehydration on the physical properties of these salts.

Methods

The salts were analyzed by X-ray powder diffraction (XRPD), single crystal X-ray and polarized light microscopy (PLM).

Results

Our research was able to identify three general behaviors of the desolvation of calcium salts of carboxylic acids. Upon desolvation, ethanolate and pentahydrate calcium indomethacin (CaIndo and CaInd2, respectively) stayed crystalline, fenoprofen calcium (CaFEN), calcium ketoprofen (CaKTN), calcium salicylate (CaSAL), calcium mefenamate (CaMEF) and calcium tolfenamate (CaTOLF) became mesophases, while calcium diflunisal became partially crystalline. On the other hand, the solubility studies of CaFEN, CaKTN and CaSAL showed that all dehydrated calcium salts had higher solubility than their crystalline counterparts and amorphous CaKTN had higher solubility than mesomorphous CaKTN.

Conclusions

Several factors influence the desolvation behavior of calcium salts. We believe the flexibility of the benzene rings in CaKTN, CaFEN, CaMEF and CaTOLF was important for these products to become mesomorphous when they loose their crystalline water; meanwhile, CaDIF where the two benzene rings are coplanar remained crystalline when heated. Additionally, the existence of water channels and the hydrogen bonding networks in the crystals is hypothesized to play an important role in the desolvation behavior of these materials.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. A. Terakita and S. R. Byrn. Structure and physical stability of hydrates and thermotropic mesophase of calcium benzoate. J. Pharm. Sci. 95:1162–1172 (2006).

    Google Scholar 

  2. The United States Pharmacopoeia, 28th revision, United States Pharmacopeial Convention, Rockville, U.S.A., 2005, p. 2513.

  3. G. R. Desiraju. In search of clarity. Nature 423:485 (2003).

    Article  PubMed  CAS  Google Scholar 

  4. J. Patterson, A. Bary, and T. Rades. Physical stability and solubility of the thermotropic mesophase of fenoprofen calcium as pure drug and in a tablet formulation. Int. J. Pharm. 247:147–157 (2002).

    Article  PubMed  CAS  Google Scholar 

  5. J. S. G. Cox, G. D. Woodard, and W. McCrone. Solid-state chemistry of cromolyn sodium (disodium cromoglycate). J. Pharm. Sci. 60:1485 (1971).

    Google Scholar 

  6. E. Vadas, P. Toma, and G. Zografi. Solid-state phase transition initiated by water vapor sorption of crystalline L-660,711, a leukotriene D4 receptor antagonist. Pharm. Res. 8:148–155 (1991).

    Article  PubMed  CAS  Google Scholar 

  7. T. Rades, Y. Padmadisastra, and C. Muller-Goymann. Thermal behavior and solubility of fenoprofen calcium. Pharmazie 51:846–851 (1996).

    CAS  Google Scholar 

  8. D. Lechuga-Ballesteros, A. Abdul-Fattah, C. Stevenson, and D. B. Bennett. Properties and stability of a liquid crystal form of Cyclosporin—the first reported naturally occurring peptide that exists as a thermotropic liquid crystal. J. Pharm. Sci. 92:1821–1831 (2003).

    Article  PubMed  CAS  Google Scholar 

  9. D. Lechhuga-Ballesteros, A. Abdul-Fattah, Y. Liang, D. P. Miller, C. L. Stevenson, J. Zhang, and D. B. Bennett. Liquid crystallinity improves the physical stability of spray dried powders for inhalation. Respir. Drug Delivery IX 569–571 (2004).

  10. C. J. Strachan, T. Rades, D. A. Newnham, K. C. Gordon, M. Pepper, and P. F. Taday. Using terahertz pulsed spectroscopy to study crystallinity of pharmaceutical materials. Chem. Phys. Lett. 390:20–24 (2004).

    Article  CAS  Google Scholar 

  11. C. L. Stevenson, M. M. Tan, and D. Lechuga-Ballesteros. Secondary structure of cyclosporine in spray-dried liquid crystal by FTIR. J. Pharm. Sci. 92:1832–1843 (2003).

    Article  PubMed  CAS  Google Scholar 

  12. H. Bunjes, and T. Rades. Thermotropic liquid crystalline drugs. J. Pharm. Pharmacol. 57:807–816 (2005).

    Article  PubMed  CAS  Google Scholar 

  13. C. L. Stevenson, D. B. Bennett, and D. Lechuga-Ballesteros. Pharmaceutical liquid crystals: the relevance of partially ordered systems. J. Pharm. Sci. 94:1861–1880 (2005).

    Article  PubMed  CAS  Google Scholar 

  14. M. Pavlov, P. E. M. Siegbahn, and M. Sandstrom. Hydration of beryllium, magnesium, calcium, and zinc ions using density functional theory. J. Phys. Chem. 102:219–228 (1998).

    CAS  Google Scholar 

  15. R. Debuyst, F. Dejehet, and M. Dekandelaer. Determination des structures crystalline et moleculaire des salicylates de calcium et de strontium dehydrates. Etude par resonance paramagnetique electronique du cuivre (II) incorpore a ces composes de coordination huit. J. Chim. Phys. 76:1117–1124 (1979).

    CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the financial support from the Purdue–Michigan Solid State Program.

Author information

Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA

    Faraj Atassi & Stephen R. Byrn

Authors
  1. Faraj Atassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen R. Byrn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen R. Byrn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Atassi, F., Byrn, S.R. General Trends in the Desolvation Behavior of Calcium Salts. Pharm Res 23, 2405–2412 (2006). https://doi.org/10.1007/s11095-006-9015-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-006-9015-4

Key words

Search

Navigation