Deposits from Creams Containing 20% (w/w) Urea and Suppression of Crystallization (Part 1): Rate of Crystallization from Cream Containing 20% (w/w) Urea and Evaluation of the Properties of the Deposit

Chem Pharm Bull (Tokyo). 2016;64(8):1084-91. doi: 10.1248/cpb.c15-00782.


Two creams containing 20% (w/w) urea and various emulsifiers, a nonionic surfactant (NS) and lecithin (LEC), were prepared, and the rate of crystallization following application of the cream and differences in the properties of the deposits were investigated. Post-application crystallization was slower with the LEC formulation. Differences in the crystals obtained from the two formulations and from a 20% aqueous solution of urea were evaluated by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), powder X-ray-DSC (PXRD-DSC) and Fourier transform infrared spectrophotometry (FT-IR). PXRD and PXRD-DSC measurements showed that the diffraction patterns of both formulations differed from that of urea. The NS formulation provided diffraction peaks for urea and a urea composite, whereas only the urea composite was evident in the LEC formulation. DSC scans of urea showed an endotherm at around 134°C, whereas the deposits from both formulations provided an endotherm 23-25°C below that of urea; the NS formulation also showed a peak at around 140°C. These results indicate a tendency for urea crystallization in the NS formulation. FT-IR measurements showed that both deposits have a urea-based structure. The effects of the LEC formulation components on the physical properties of urea were investigated by PXRD and showed that all diffraction peaks were evenly weakened, suggesting that urea tends to be amorphous and that the formulation impacts post-application urea crystallization. Consequently, the amorphous state of urea can be maintained post-application by optimizing the formulation, thereby increasing the clinical efficacy of the cream.

MeSH terms

  • Crystallization
  • Emulsions / chemistry
  • Lecithins / chemical synthesis
  • Lecithins / chemistry*
  • Surface-Active Agents / chemical synthesis
  • Surface-Active Agents / chemistry*
  • Urea / chemistry*


  • Emulsions
  • Lecithins
  • Surface-Active Agents
  • Urea