title: Prediction of acetaminophen's solubility in poly(ethylene oxide) at room temperature using the Flory-Huggins theory.
abstract: 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.
authors.affiliation: The Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07102, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Costas
authors.initials: C
authors.lastname: Gogos
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D008956:Models, Chemical; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D000082:Acetaminophen; D011092:Polyethylene Glycols