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

Abstract

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 T and T, 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 does not correlate with the onset of recrystallization under the experimental storage conditions. However, a clear correlation between T and the onset of recrystallization was observed. It is shown that at storage temperature below T, 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.

Ultrasensitive Microstring Resonators for Solid State Thermomechanical Analysis of Small and Large Molecules

“…Depending on the measurement, absolute T g values can differ significantly, as for example seen by constantly higher values recorded by DMA than DSC for the same materials. 21,32 This variation in signal response is also underlined by the fact that a small deviation from the reference slope for MTA-F can already be noticed at values closer to the DSC midpoint T g values. This deviation is more pronounced in polymer samples and further discussed in the respective section below.…”

“…23 The alpha re-laxation (or glass transition, T g ) has previously been described as an important indicator for amorphous stability. 22 Moreover, recent focus of physico-chemical investigation of glassy materials is also including the beta relaxation 24 (T β ), which is only accessible by more sensitive measuring techniques than mDSC, that require bulk sample sizes (> 100 mg) such as Dielectric Spectroscopy 25 and DMA 21 or more advanced vibrational spectroscopic techniques such as Terahertz Spectroscopy. 26 In this study, we also present sensitive measurements of the T g of polymers.…”

Influence of Green Tea and Basil Extracts on Cassava Starch Based Films as Assessed by Thermal Degradation, Crystalline Structure, and Mechanical Properties

“…The important peak observed in Figure , in the range of −58 and −63 °C, is associated to the glycerol‐rich phase main relaxation whereas a wide and low‐intensity peak was observed between 10 and 26 °C attributed to the starch‐rich phase glass transition. Both relaxation peaks shifted to lower temperatures when the extracts were incorporated and the relaxation of the starch‐rich phase also widened.…”

Correlation between molecular dynamics and physical stability of two milled anhydrous sugars: Lactose and sucrose

“…Parameters such as structural relaxation time, enthalpy relaxation time, glass transition and/or fragility index (obtained from dielectric spectroscopy, DSC or isothermal micro-calorimetry techniques) have been used to provide certain measures of molecular mobility (Aso et al, 2000;Graeser et al, 2009;Kawai et al, 2005;Pokharkar et al, 2006;Rodrigues et al, 2013).Recently, Tg of β-relaxation (Kissi et al, 2018) and THz spectroscopy (Sibik et al, 2015;Sibik et al, 2016)have also been employed to study molecular mobility and crystallization dynamics of amorphous phase.…”