Determination of acetaminophen's solubility in poly(ethylene oxide) by rheological, thermal and microscopic methods

Min Yang, Peng Wang, Herman Suwardie, Costas Gogos

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


A drug's solubility in a polymeric excipient is an important parameter that dictates the process window of hot-melt extrusion (HME) and product stability during storage. However, it is rather challenging to experimentally determine the solubility and there is very few published work in this field. In this study, the solubility of a model drug acetaminophen (APAP) in a pharmaceutical grade polymer poly(ethylene oxide) (PEO) at HME processing temperature was measured utilizing rheological analysis, hot-stage microscopy and differential scanning calorimetry (DSC). The results from three methods were consistent and the solubility was found to increase from 14% at 80 °C to 41% at 140 °C. The apparent drug solubility at room temperature was estimated to be less than 10% through glass transition temperature (Tg) measurement using DSC and dynamic mechanical thermal analysis (DMTA). A "phase diagram" was constructed based on the experimental data and could be explored to design the HME process and formulation. Very few assumptions were made in the experimental study and result analysis, and the methods described here can be applied to investigate other drug-polymer systems to obtain the important thermodynamic data.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalInternational Journal of Pharmaceutics
Issue number1-2
StatePublished - Jan 17 2011

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Acetaminophen/ paracetamol
  • Glass transition
  • Hot-melt mixing
  • Poly(ethylene oxide) (PEO)
  • Rheology
  • Solubility


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