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AAPS PharmSciTech. 2016 April; 17(2): 318–327.
Published online 2015 June 20. doi:  10.1208/s12249-015-0343-8
PMCID: PMC4984891

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

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.

KEY WORDS: amorphous solid dispersion, Flory–Huggins interaction parameter, miscibility, phase diagram, physical stability

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists