Effect of experimental and sample factors on dehydration kinetics of mildronate dihydrate: mechanism of dehydration and determination of kinetic parameters

J Pharm Sci. 2014 Jun;103(6):1747-55. doi: 10.1002/jps.23972. Epub 2014 Apr 11.

Abstract

The dehydration kinetics of mildronate dihydrate [3-(1,1,1-trimethylhydrazin-1-ium-2-yl)propionate dihydrate] was analyzed in isothermal and nonisothermal modes. The particle size, sample preparation and storage, sample weight, nitrogen flow rate, relative humidity, and sample history were varied in order to evaluate the effect of these factors and to more accurately interpret the data obtained from such analysis. It was determined that comparable kinetic parameters can be obtained in both isothermal and nonisothermal mode. However, dehydration activation energy values obtained in nonisothermal mode showed variation with conversion degree because of different rate-limiting step energy at higher temperature. Moreover, carrying out experiments in this mode required consideration of additional experimental complications. Our study of the different sample and experimental factor effect revealed information about changes of the dehydration rate-limiting step energy, variable contribution from different rate limiting steps, as well as clarified the dehydration mechanism. Procedures for convenient and fast determination of dehydration kinetic parameters were offered.

Keywords: dehydration; isoconversional methods; kinetic model; kinetics; mathematical model; particle size; thermal analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Agents / chemistry*
  • Kinetics
  • Methylhydrazines / chemistry*
  • Particle Size
  • Water / chemistry*

Substances

  • Cardiovascular Agents
  • Methylhydrazines
  • Water
  • 3-(2,2,2-trimethylhydrazine)propionate