title: Micro-scale prediction method for API-solubility in polymeric matrices and process model for forming amorphous solid dispersion by hot-melt extrusion.
abstract: A new predictive micro-scale solubility and process model for amorphous solid dispersions (ASDs) by hot-melt extrusion (HME) is presented. It is based on DSC measurements consisting of an annealing step and a subsequent analysis of the glass transition temperature (Tg). The application of a complex mathematical model (BCKV-equation) to describe the dependency of Tg on the active pharmaceutical ingredient (API)/polymer ratio, enables the prediction of API solubility at ambient conditions (25°C). Furthermore, estimation of the minimal processing temperature for forming ASDs during HME trials could be defined and was additionally confirmed by X-ray powder diffraction data. The suitability of the DSC method was confirmed with melt rheological trials (small amplitude oscillatory system). As an example, ball milled physical mixtures of dipyridamole, indomethacin, itraconazole and nifedipine in poly(vinylpyrrolidone-co-vinylacetate) (copovidone) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) were used.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany.
authors.forename: Esther S
authors.initials: ES
authors.lastname: Bochmann
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany; Scientific Consilience GmbH, Saarbrücken, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Neumann
authors.affiliation: Global Technical Marketing Solubilization, BASF SE, Ludwigshafen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Gryczke
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany. Electronic address: kgwagner@uni-bonn.de.
authors.forename: Karl G
authors.initials: KG
authors.lastname: Wagner
mesh_terms: D002626:Chemistry, Pharmaceutical; D006358:Hot Temperature; D011108:Polymers / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility
chemical_list: D011108:Polymers
keywords: Amorphous solid dispersion; DSC; Dipyridamole (PubChem CID: 3108); Hot-melt extrusion; Indomethacin (PubChem CID: 3715); Itraconazole (PubChem CID: 55283); Melt rheology; Nifedipine (PubChem CID: 4485); Solubility