title: 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, χ d-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 (ΔG mix) 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.
authors.affiliation: GVM College of Pharmacy, Sonipat, Haryana, 131001, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Bansal
authors.affiliation: Khalsa College of Pharmacy, Amritsar, Punjab, 143001, India.
authors.forename: Uttam Singh
authors.initials: US
authors.lastname: Baghel
authors.affiliation: GVM College of Pharmacy, Sonipat, Haryana, 131001, India. sthakral109@gmail.com.|College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455, USA. sthakral109@gmail.com.
authors.forename: Seema
authors.initials: S
authors.lastname: Thakral
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013696:Temperature; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004364:Pharmaceutical Preparations; D011108:Polymers
keywords: Flory–Huggins interaction parameter; amorphous solid dispersion; miscibility; phase diagram; physical stability