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

作者：Kissi Eric Ofosu; Grohganz Holger; Lobmann Korbinian; Ruggiero Michael T^*; Zeider J Axel; Rades Thomas^*

来源：Journal of Physical Chemistry B, 2018, 122(10): 2803-2808.

DOI：10.1021/acs.jpcb.7b10105

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, alpha-relaxation and beta-relaxation processes with the associated transition temperatures T-g alpha and T-g beta, 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, T-g alpha does not correlate with the onset of recrystallization under the experimental storage conditions. However, a clear correlation between T-g beta and the onset of recrystallization was observed. It is shown that at storage temperature below T-g beta, 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.

• 出版日期2018-3-15