Archives of Pharmacal Research

, Volume 7, Issue 1, pp 47–52

Pharmaceutical studies on the polymorphism of hydrochlorothiazide

  • Bong Hee Kim
  • Johng Kap Kim
Original Articles

DOI: 10.1007/BF02856921

Cite this article as:
Kim, B.H. & Kim, J.K. Arch. Pharm. Res. (1984) 7: 47. doi:10.1007/BF02856921


Four polymorphic forms (I, II, III and IV) of hydrochlorothiazide have been characterized on the basis of x-ray diffractometry and differential thermal analysis. Form I was obtained by crystallization from N,N-dimethylformamide and Form II was crystallized from hot methanol. Form III was precipitated from sodium hydroxide aqueous solution by treatment with hydrochloric acid and Form IV was crystallized from 50% methanol. The metastable form I was a most stable form among four polymorphs, which was stable more than ten months at room temperature. The thermodynamic parameters such as heat of solution, enthalpy, entropy, free energy difference and transition temperature were determined by the measurement of intrinsic dissolution rate. The transition temperature and the heat of transition between the metastable Form I and Form II were determined to be 299.15°K and 5.03 Kcal/mole, respectively and free energy difference (δF) was 302.13 cal/mole. Diuretic action of these four polymorphic forms was also evaluated by monitoring the difference in urinary excretion of sodium, potassium and magnesium in rats.


Hydrochlorothiazide Polymorphs Differential thermal analysis x-Ray powder diffractometry Transition temperature Heat of transition 

Copyright information

© The Pharmaceutical Society of Korea 1984

Authors and Affiliations

  • Bong Hee Kim
    • 1
  • Johng Kap Kim
    • 2
  1. 1.Department of PharmacyChung-Nam National UniversityDaejeon
  2. 2.College of PharmacyChung Ang UniversitySeoul 151Korea

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