Glass forming ability of amorphous drugs investigated by continuous cooling- and isothermal transformation

Lasse Ingerslev Blaabjerg; Eleanor Lindenberg; Korbinian Löbmann; Holger Grohganz; Thomas Rades

doi:10.1021/acs.molpharmaceut.6b00650

Glass forming ability of amorphous drugs investigated by continuous cooling- and isothermal transformation

Lasse Ingerslev Blaabjerg, Eleanor Lindenberg, Korbinian Löbmann, Holger Grohganz, Thomas Rades

19 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Molecular Pharmaceutics
Vol/bind	13
Udgave nummer	9
Sider (fra-til)	3318-3325
Antal sider	8
ISSN	1543-8384
DOI	https://doi.org/10.1021/acs.molpharmaceut.6b00650
Status	Udgivet - 6 sep. 2016

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10.1021/acs.molpharmaceut.6b00650

Citationsformater

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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.",

author = "Blaabjerg, {Lasse Ingerslev} and Eleanor Lindenberg and Korbinian L{\"o}bmann and Holger Grohganz and Thomas Rades",

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doi = "10.1021/acs.molpharmaceut.6b00650",

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TY - JOUR

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 - 2016/9/6

Y1 - 2016/9/6

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

SN - 1543-8384

VL - 13

SP - 3318

EP - 3325

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

IS - 9

ER -

Glass forming ability of amorphous drugs investigated by continuous cooling- and isothermal transformation

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