title: Relating solubility data of parabens in liquid PEG 400 to the behaviour of PEG 4000-parabens solid dispersions.
abstract: The solid state behaviour of polyethylene glycol 4000 (PEG 4000) and dispersions of a homologous series of parabens (methyl- (MP), ethyl- (EP), propyl- (PP) and butyl- (BP)) were examined and compared to the paraben solubility in liquid PEG 400. Dispersions were prepared by co-melting different amounts of paraben (5-80% (w/w)) and PEG 4000 and were studied using a combination of differential scanning calorimetry (DSC) and small and wide angle X-ray diffraction (SAXD/WAXD). Depending on the concentration of parabens in the dispersions, DSC showed melting peaks from folded and unfolded forms of PEG, a eutectic melting and melting of pure parabens. The fraction of folded PEG increased and the melting temperatures of both PEG forms decreased with increasing paraben content. In an apparent phase diagram of PP-PEG dispersions a eutectic mixture appeared above 5% PP. In addition, a melting peak corresponding to the paraben appeared for dispersion containing more than 60% PP. Similar phase diagrams were shown for the other parabens. The SAXD data and a 1D correlation function analysis revealed that MP and BP were incorporated into the amorphous domains of the lamellae of solid PEG to a higher degree than EP and PP. In addition, the lamellae thickness of PEG and the fraction of amorphous domains increased more for MP and BP compared to EP and PP. BP showed the highest solubility of the parabens followed by MP, EP and PP in both liquid and solid PEG. Furthermore, the thickness of the amorphous domains of the PEG in the different parabens-PEG dispersions could be correlated to the solubility in liquid PEG 400.
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Unga
authors.forename: Farhad
authors.initials: F
authors.lastname: Tajarobi
authors.forename: Ove
authors.initials: O
authors.lastname: Norder
authors.forename: Göran
authors.initials: G
authors.lastname: Frenning
authors.forename: Anette
authors.initials: A
authors.lastname: Larsson
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004337:Drug Carriers; D004339:Drug Compounding; D008968:Molecular Conformation; D010226:Parabens / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D004304:Dosage Forms; D004337:Drug Carriers; D010226:Parabens; D012996:Solutions; C012313:ethyl-p-hydroxybenzoate; C038091:butylparaben; D011092:Polyethylene Glycols; C015358:methylparaben; C006068:propylparaben