Effect of water activity and temperature on the stability of creatine during storage

Drug Dev Ind Pharm. 2009 Aug;35(8):1003-8. doi: 10.1080/03639040902755197.


Creatine degradation to creatinine, which has no biological activity, in combinations of glycerol and pH 4.0 buffer solutions followed first-order kinetics up to a point where degradation started to level off, generally beyond the first half-life. Practical data are reported for a wide range of water activity (a(w)) values (0.31-0.983) at 4 degrees C, 23 degrees C, and 35 degrees C. Creatine degradation did not exhibit a dilution effect, that is a decrease in rate about an a(w) of 0.7, as is found for both microbiological growth and chemical reactions in semisolid food matrix systems. The temperature dependence obeyed the Arrhenius relationship with an energy of activation of about 20 kcal/mol at a(w) >or= 0.68 increasing to 23 kcal/mole below that a(w). In addition, a semilog plot of half-life as a function of a(w) at each temperature follows a predicted straight line. The pH and assumed liquid viscosity increase through increased glycerol concentration were not able to completely explain the decrease in rate of degradation as a function of a(w). Furthermore, we confirmed that creatine stability in the crystal form is very high as long as it does not reach the deliquescence state.

MeSH terms

  • Creatine / chemistry*
  • Crystallization
  • Drug Stability
  • Drug Storage
  • Glycerol / chemistry*
  • Half-Life
  • Hydrogen-Ion Concentration
  • Kinetics
  • Temperature
  • Viscosity
  • Water / chemistry*


  • Water
  • Creatine
  • Glycerol