Glass forming ability of amorphous drugs investigated by continuous cooling- and isothermal transformation
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Glass forming ability of amorphous drugs investigated by continuous cooling- and isothermal transformation. / Blaabjerg, Lasse Ingerslev; Lindenberg, Eleanor; Löbmann, Korbinian; Grohganz, Holger; Rades, Thomas.
In: Molecular Pharmaceutics, Vol. 13, No. 9, 2016, p. 3318-3325.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Glass forming ability of amorphous drugs investigated by continuous cooling- and isothermal transformation
AU - Blaabjerg, Lasse Ingerslev
AU - Lindenberg, Eleanor
AU - Löbmann, Korbinian
AU - Grohganz, Holger
AU - Rades, Thomas
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
U2 - 10.1021/acs.molpharmaceut.6b00650
DO - 10.1021/acs.molpharmaceut.6b00650
M3 - Journal article
VL - 13
SP - 3318
EP - 3325
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 9
ER -
ID: 164999334