title: Glass Forming Ability of Amorphous Drugs Investigated by Continuous Cooling and Isothermal Transformation.
abstract: The aim of this study was to investigate the glass forming ability of 12 different drugs by the determination of continuous cooling and isothermal transformation diagrams in order to elucidate if an inherent differentiation between the drugs with respect to their the glass forming ability can be made. Continuous-cooling-transformation (CCT) and time-temperature-transformation (TTT) diagrams of the drugs were developed in order to predict the critical cooling rate necessary to convert the drug from the melt into an amorphous form. While TTT diagrams overestimated the actual critical cooling rate, they allowed an inherent differentiation of glass forming ability for the investigated drugs into drugs that are extremely difficult to amorphize (>750 °C/min), drugs that require modest cooling rates (>10 °C/min), and drugs that can be made amorphous even at very slow cooling rates (>2 °C/min). Thus, the glass forming ability can be predicted by the use of TTT diagrams. In contrast to TTT diagrams, CCT diagrams may not be suitable for small organic molecules due to poor separation of exothermic events, which makes it difficult to determine the zone of recrystallization. In conclusion, this study shows that glass forming ability of drugs can be predicted by TTT diagrams.
authors.affiliation: Department of Pharmacy, University of Copenhagen , Universitetsparken 2, 2100 Copenhagen, Denmark.|Actelion Pharmaceuticals Ltd , Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
authors.forename: Lasse I
authors.initials: LI
authors.lastname: Blaabjerg
authors.affiliation: Actelion Pharmaceuticals Ltd , Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Lindenberg
authors.affiliation: Department of Pharmacy, University of Copenhagen , Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Korbinian
authors.initials: K
authors.lastname: Löbmann
authors.affiliation: Department of Pharmacy, University of Copenhagen , Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Holger
authors.initials: H
authors.lastname: Grohganz
authors.affiliation: Department of Pharmacy, University of Copenhagen , Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D005898:Glass / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D004364:Pharmaceutical Preparations
keywords: CCT diagram; TTT diagram; amorphous; classification; critical cooling rate