Miscibility studies of indomethacin and Eudragit® E PO by thermal, rheological, and spectroscopic analysis

Huiju Liu, Xueyan Zhang, Herman Suwardie, Peng Wang, Costas G. Gogos

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

The objective of this study is to understand the underlying mechanisms responsible for the superior stability of indomethacin (INM)-Eudragit® E PO (E PO) system by exploring the miscibility and intermolecular interactions through the combination of thermal, rheological, and spectroscopic analysis. The zero shear-rate viscosity drops monotonically with the increase of INM concentration at 145°C, suggesting that E PO and INM form a solution and the small molecular drug acts as a plasticizer. Flow activation energy was calculated from the viscosity data at different temperature. The glass transition temperature (Tg) of the mixture at different composition was determined using differential scanning calorimetry. The Tg and flow activation energy peak at the INM concentration around 60%-70%. Fourier transform infrared analysis provided direct evidence for the intermolecular ionic interactions, which may disrupt the dimer formation of amorphous INM. The study explained the superior stability of INM-E PO mixtures, and demonstrated that a combination of thermal, rheological, and spectroscopic technologies can help us to obtain a full picture of the drug-polymer interactions and to determine the formulation and processing conditions.

Original languageEnglish (US)
Pages (from-to)2204-2212
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume101
Issue number6
DOIs
StatePublished - Jun 2012

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Eudragit® E PO
  • Glass transition
  • Indomethacin
  • Ionic interactions
  • Molecular interactions
  • Rheology
  • Solid dispersion
  • Spectroscopy
  • Stability
  • Thermal analysis

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