Mechanism of eutectic formation upon compaction and its effects on tablet properties

Mingda Bi, Sung Joo Hwang, Kenneth R. Morris

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)


The unique property of a eutectic mixture is a lower melting temperature than that of any of its pure components. What differentiates a eutectic mixture from a simple physical mixture is less well understood. This impedes the ability to anticipate and/or detect unintentional eutectic formation during pharmaceutical tablet manufacturing and any potential negative impact. In this study, a thermodynamic/heat transfer approach was used to explain the mechanism of eutectic formation upon exposure to a physical stress, i.e. compaction, and a differential scanning calorimetric (DSC) method was developed to detect and quantify the amount of eutectic formed in the compacts. Furthermore, the mechanism of eutectic formation upon compaction was tested experimentally by correlating the amount of eutectic formed in tablets with the particle size, compaction force, the estimated intimate contact area between the eutectic-forming materials, calculated tablet tensile strength, and tablet porosity. The effect of the presence of eutectics on tablet properties was also investigated. The results show that intimate contact and mutual solubility between eutectic-forming materials are the necessary and sufficient criteria for eutectic formation upon compaction. The systems of acetaminophen (APAP)/caffeine and APAP/propylphenazone were both shown to exhibit eutectic behavior upon compaction and the extent of formation was dependent upon the amount of intimate contact between eutectic-forming materials. Finally, it was found that eutectic had no negative effect on tablet hardness.

Original languageEnglish
Pages (from-to)213-226
Number of pages14
JournalThermochimica Acta
Issue number1-2
Publication statusPublished - 2003 Sept 4

Bibliographical note

Funding Information:
The authors acknowledge the financial support of the Purdue Research Foundation and the Purdue-Wisconsin Program for the study of the physical and chemical stability of pharmaceutical solid for this research.

All Science Journal Classification (ASJC) codes

  • Instrumentation
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry


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