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

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.