Construction and Validation of Binary Phase Diagram for Amorphous Solid Dispersion Using Flory–Huggins Theory

Krishna Bansal, Uttam Singh Baghel, Seema Thakral

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Drug–polymer miscibility is one of the fundamental prerequisite for the successful design and development of amorphous solid dispersion formulation. The purpose of the present work is to provide an example of the theoretical estimation of drug–polymer miscibility and solubility on the basis of Flory–Huggins (F–H) theory and experimental validation of the phase diagram. The F–H interaction parameter, χd-p, of model system, aceclofenac and Soluplus, was estimated by two methods: by melting point depression of drug in presence of different polymer fractions and by Hildebrand and Scott solubility parameter calculations. The simplified relationship between the F–H interaction parameter and temperature was established. This enabled us to generate free energy of mixing (ΔGmix) curves for varying drug–polymer compositions at different temperatures and finally the spinodal curve. The predicted behavior of the binary system was evaluated through X-ray diffraction, differential scanning calorimetry, and in vitro dissolution studies. The results suggest possibility of employing interaction parameter as preliminary tool for the estimation of drug–polymer miscibility.

Original languageEnglish (US)
Pages (from-to)318-327
Number of pages10
JournalAAPS PharmSciTech
Volume17
Issue number2
DOIs
StatePublished - Apr 1 2016

Keywords

  • Flory–Huggins interaction parameter
  • amorphous solid dispersion
  • miscibility
  • phase diagram
  • physical stability

Fingerprint Dive into the research topics of 'Construction and Validation of Binary Phase Diagram for Amorphous Solid Dispersion Using Flory–Huggins Theory'. Together they form a unique fingerprint.

Cite this