Glass-Transition Temperature of the β-Relaxation as the Major Predictive Parameter for Recrystallization of Neat Amorphous Drugs

TY - JOUR

T1 - Glass-Transition Temperature of the β-Relaxation as the Major Predictive Parameter for Recrystallization of Neat Amorphous Drugs

AU - Kissi, Eric Ofosu

AU - Grohganz, Holger

AU - Löbmann, Korbinian

AU - Ruggiero, Michael T

AU - Zeitler, J Axel

AU - Rades, Thomas

PY - 2018/3/15

Y1 - 2018/3/15

N2 - Recrystallization of amorphous drugs is currently limiting the simple approach to improve solubility and bioavailability of poorly water-soluble drugs by amorphization of a crystalline form of the drug. In view of this, molecular mobility, α-relaxation and β-relaxation processes with the associated transition temperatures Tgαand Tgβ, was investigated using dynamic mechanical analysis (DMA). The correlation between the transition temperatures and the onset of recrystallization for nine amorphous drugs, stored under dry conditions at a temperature of 296 K, was determined. From the results obtained, Tgαdoes not correlate with the onset of recrystallization under the experimental storage conditions. However, a clear correlation between Tgβand the onset of recrystallization was observed. It is shown that at storage temperature below Tgβ, amorphous nifedipine retains its amorphous form. On the basis of the correlation, an empirical correlation is proposed for predicting the onset of recrystallization for drugs stored at 0% RH and 296 K.

AB - Recrystallization of amorphous drugs is currently limiting the simple approach to improve solubility and bioavailability of poorly water-soluble drugs by amorphization of a crystalline form of the drug. In view of this, molecular mobility, α-relaxation and β-relaxation processes with the associated transition temperatures Tgαand Tgβ, was investigated using dynamic mechanical analysis (DMA). The correlation between the transition temperatures and the onset of recrystallization for nine amorphous drugs, stored under dry conditions at a temperature of 296 K, was determined. From the results obtained, Tgαdoes not correlate with the onset of recrystallization under the experimental storage conditions. However, a clear correlation between Tgβand the onset of recrystallization was observed. It is shown that at storage temperature below Tgβ, amorphous nifedipine retains its amorphous form. On the basis of the correlation, an empirical correlation is proposed for predicting the onset of recrystallization for drugs stored at 0% RH and 296 K.

U2 - 10.1021/acs.jpcb.7b10105

DO - 10.1021/acs.jpcb.7b10105

M3 - Journal article

C2 - 29498523

SN - 1520-6106

VL - 122

SP - 2803

EP - 2808

JO - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical

JF - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical

IS - 10

ER -