Prediction of acetaminophen's solubility in poly(ethylene oxide) at room temperature using the Flory-Huggins theory

Min Yang, Peng Wang, Costas Gogos

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Solid dispersion technologies such as hot-melt extrusion and spray drying are often used to enhance the solubility of poorly soluble drugs. The biggest challenge associated with solid dispersion systems is that amorphous drugs may phase-separate from the polymeric matrix and recrystallize during storage. A more fundamental understanding of drug-polymer mixtures is needed for the industry to embrace the solid dispersion technologies. In this study, a theoretical model based on Flory-Huggins lattice theory was utilized to predict the solubility of a model drug acetaminophen (APAP) in a semi-crystalline polymer poly(ethylene oxide) (PEO) at 300 K. The interaction parameter χ was calculated to be -1.65 from the depression of drug's melting temperature determined from rheological and differential scanning calorimetry analysis. The equilibrium solubility in amorphous PEO was estimated to be 11.7% at 300 K. Assuming no APAP molecules dissolve in the crystalline part of PEO, the adjusted theoretical solubility is around 2.3% considering PEO being 80% crystalline. The solubility of APAP in PEG 400 was calculated to be 14.6% by using the same χ value, close to the experimental measurement 17.1%. The drug's solubility could be altered noticeably by the change of both χ and polymer molecular weight. The study also suggests that the depression of drug's melting point is a good indicator for preliminary polymer screening. The polymer that reduces the melting point the most is likely to be most miscible with the drug.

Original languageEnglish (US)
Pages (from-to)102-108
Number of pages7
JournalDrug Development and Industrial Pharmacy
Issue number1
StatePublished - Jan 2013

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry


  • Acetaminophen/paracetamol
  • Flory-Huggins interaction parameter χ
  • Hot-melt extrusion
  • Poly(ethylene oxide)
  • Solid dispersion
  • Solubility


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