Effects of solvents and crystallization conditions on the polymorphic behaviors and dissolution rates of valsartan

Arch Pharm Res. 2012 Jul;35(7):1223-30. doi: 10.1007/s12272-012-0713-7. Epub 2012 Aug 3.

Abstract

For the quality evaluation of raw materials, the influence of various types of solvents on the polymorphic crystallization behaviors and dissolution rates of two sources of valsartan (VAL) from China and India was investigated. Samples were prepared by recrystallization from water or organic solvents, such as acetonitrile, acetone and ethanol, using methods with and without heating. Recrystallization behaviors were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Scanning electron microscopy (SEM) was also used to observe the morphology of samples. The dissolution rate of recrystallized samples in water was evaluated and compared to the original VAL sample. There were significant differences in morphology, crystal structure and dissolution rate among the samples recrystallized using organic solvents. VAL was transformed into another polymorphic form by the solvents and recrystallization conditions. These physical properties of VAL also differed between the two sources of VAL. Thus, the physicochemical differences of raw materials should be carefully considered in early dosage formulation approaches.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetone / chemistry
  • Acetonitriles / chemistry
  • Angiotensin II Type 1 Receptor Blockers / chemistry*
  • Calorimetry, Differential Scanning
  • Chemistry, Pharmaceutical
  • Crystallization
  • Crystallography, X-Ray
  • Ethanol / chemistry
  • Hot Temperature
  • Kinetics
  • Microscopy, Electron, Scanning
  • Powder Diffraction
  • Powders
  • Solubility
  • Solvents / chemistry*
  • Technology, Pharmaceutical / methods
  • Tetrazoles / chemistry*
  • Valine / analogs & derivatives*
  • Valine / chemistry
  • Valsartan
  • Water / chemistry

Substances

  • Acetonitriles
  • Angiotensin II Type 1 Receptor Blockers
  • Powders
  • Solvents
  • Tetrazoles
  • Water
  • Acetone
  • Ethanol
  • Valsartan
  • Valine
  • acetonitrile