Pharmaceutical Research

, 36:159 | Cite as

Gel Formation Induced Slow Dissolution of Amorphous Indomethacin

  • Weili Heng
  • Yuanfeng Wei
  • Yifan Xue
  • Hao Cheng
  • Linghe Zhang
  • Jianjun Zhang
  • Yuan GaoEmail author
  • Shuai QianEmail author
Research Paper



Amorphous indomethacin (IMC) forms gel with a decreased dissolution behavior compared to crystalline IMC during dissolution. The current study aims to explore gelation mechanism and attempt to eliminate gelling effect by formulation development.


Amorphous IMC was prepared by melt-quenching method. Dissolution tests of amorphous IMC were performed at various temperatures under sink condition. The formed gels were characterized by PLM, SEM, DSC and XRPD.


Amorphous IMC exhibited an initial higher dissolution followed by a decreased dissolution lower than its crystalline counterpart at 32 and 37°C, and even a much lower dissolution during the whole dissolution period at 45°C. Meanwhile, a viscous soft mass (“gel”) was observed to adhere upon the paddle or wall of the vessel. The formed gel could be characterized as a three-dimensional dense micro-fiber structure under SEM. The gel formation was proposed to be related to the decreased Tg of amorphous IMC when contacting aqueous medium, resulting in entering into supercooled liquid state with high viscosity. The addition of hydrophilic silica accelerated gel formation, while mixing with hydrophobic silica was able to weaken and even eliminate the gelation, and hence significantly enhancing dissolution.


The present study recommends that gel formation should be included in the investigation of amorphous materials in order to find ways for resolving defects of amorphous materials while keeping their advantages in pharmaceutics.

Key words

amorphous degelation dissolution gel formation indomethacin 



Differential scanning calorimetry




Low molecular weight organic gelators


Phosphate buffer solution


Polarized light microscopy


Relative humidity


Scanning electron microscopy


Glass transition temperature


X-ray powder diffraction


Acknowledgements and Disclosures

This research was supported by National Natural Science Foundation of China (81,703,712, 81,773,675, 81,873,012), “Double First-Class” University Project (CPU2018GY11, CPU2018GY27), Six Talent Peaks Project in Jiangsu Province, Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (TAPP), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Jiangsu Province Double Innovation Talent Program (2015), Postgraduate Research & Practice Innovation Program of Jiangsu Province. The authors thank Ms. Xiaoshuang He from School of Traditional Chinese Pharmacy (China Pharmaceutical University) for her technical supporting. The authors declare no competing financial interest.

Supplementary material

11095_2019_2700_MOESM1_ESM.docx (4.2 mb)
ESM 1 (DOCX 4339 kb)


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Authors and Affiliations

  1. 1.School of PharmacyChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  2. 2.School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  3. 3.Department of ChemistrySmith CollegeNorthamptonUSA

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