AAPS PharmSciTech

, Volume 6, Issue 1, pp E115–E119 | Cite as

Structure determination and characterization of carbendazim hydrochloride dihydrate

  • Stephen G. Machatha
  • Tapan Sanghvi
  • Samuel H. Yalkowsky


The objective of this study was to synthesize and characterize the hydrochloride salt of carbendazim with the aim of improving the intrinsic solubility of the parent compound. Carbendazim hydrochloride dihydrate was synthesized for the purpose of increasing the aqueous solubility of the parent drug, carbendazim. This was done with the commonly used saturation and cooling method. The structure was determined by single crystal radiograph crystallography, and the hydrochloride salt was found to be a dihydrate. The salt crystallized in a P 21 21 21 (#19) space group, which is typical for nonplanar, achiral, and noncentrosymmetric molecules. The asymmetric unit is comprised of 1 molecule each of carbendazim and chloride and 2 water molecules. The carbendazim molecules arrange themselves in a helical structure, with the waters and the chloride molecules in the channel linking the helix. The crystal lattice is held together by numerous hydrogen bonds, as well as van der Waals interactions. The melting point of the salt is 125.6°C. The solubility of the salt is 6.08 mg/mL, which is a thousand-fold increase from the intrinsic solubility (6.11 μg/mL) of the free base.


carbendazim dihydrate hydrochloride radiograph crystallography helical structure enantiotropic 


  1. 1.
    Ni N, Sanghvi T, Yalkowsky SH. Solubilization and preformulation of carbendazim.Int J Pharm. 2002;244:99–104.CrossRefGoogle Scholar
  2. 2.
    Hendriksen BA, Sanchez F, Bolger MB. The composite solubility versus pH profile and its role in intestinal absorption prediction.AAPS PharmSci. 2003;5:E4.CrossRefGoogle Scholar
  3. 3.
    Lipinsky CA, Lombardo FL, Dominy BW, Feeny PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.Adv Drug Del Rev. 1997;23:3–25.CrossRefGoogle Scholar
  4. 4.
    Serajuddin ATM, Pudipeddi M. Salt selection strategies. In: Stahl PH and Wermuth CG, eds.Handbook of Pharmaceutical Salts Properties Selection and Use. Verlag Helvetica Chemica Acta (Switzerland) and Wiley-VCH (Federal Republic of Germany), 2002;158–159.Google Scholar
  5. 5.
    Tong WQ, Whitesell G. In situ salt screening—a useful technique for discovery support and preformulation studies.Pharm Dev Technol. 1998;3:215–223.CrossRefGoogle Scholar
  6. 6.
    Bastin RJ, Bowker MJ, Slater BJ. Salt selection and optimization procedures for pharmaceutical new chemical entities.Org Proc Res Dev. 2000;4:427–435.CrossRefGoogle Scholar
  7. 7.
    Berge SM, Bighley LD, Monkhouse DC. Pharmaceutical salts.J Pharm Sci. 1977;66:1–19.CrossRefGoogle Scholar
  8. 8.
    Bighley LD, Berge SM, Monkhouse DC. Presevation of pharmacuetical products to salt forms of drugs and absorption. In: Swarbrick J, Boylan JC, eds.Encyclopedia of Pharmaceutical Technology 13. New York, NY: Marcel Dekker; 1996;453–499.Google Scholar
  9. 9.
    Massa W.Crystal structure determination. New York: Springer-Verlag; 2000.Google Scholar
  10. 10.
    Tong P, Zograf G. Effects of water vapor absorption on the physical and chemical stability of amorphous sodium indomethacin.AAPS PharmSciTech. 2004;5:E26.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2005

Authors and Affiliations

  • Stephen G. Machatha
    • 1
  • Tapan Sanghvi
    • 1
  • Samuel H. Yalkowsky
    • 1
  1. 1.College of PharmacyThe University of ArizonaTucson

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