TY  - JOUR
A1  - Thayumanasundaram, Savitha
A1  - Raman Venkatesan, Thulasinath
A1  - Ousset, Aymeric
A1  - Van Hollebeke, Kim
A1  - Aerts, Luc
A1  - Wubbenhorst, Michael
A1  - Van den Mooter, Guy
T1  - Complementarity of mDSC, DMA, and DRS Techniques in the Study of T-g and Sub-T-g Transitions in Amorphous Solids
BT  - PVPVA, Indomethacin, and Amorphous Solid Dispersions Based on Indomethacin/PVPVA
JF  - Molecular pharmaceutics
N2  - Recently, glasses, a subset of amorphous solids, have gained attention in various fields, such as polymer chemistry, optical fibers, and pharmaceuticals. One of their characteristic features, the glass transition temperature (T-g) which is absent in 100% crystalline materials, influences several material properties, such as free volume, enthalpy, viscosity, thermodynamic transitions, molecular motions, physical stability, mechanical properties, etc. In addition to T-g, there may be several other temperaturedependent transitions known as sub-T-g transitions (or beta-, gamma-, and delta-relaxations) which are identified by specific analytical techniques. The study of T-g and sub-T-g transitions occurring in amorphous solids has gained much attention because of its importance in understanding molecular kinetics, and it requires the combination of conventional and novel characterization techniques. In the present study, three different analytical techniques [modulated differential scanning calorimetry (mDSC), dynamic mechanical analysis (DMA), and dielectric relaxation spectroscopy (DRS)] were used to perform comprehensive qualitative/quantitative characterization of molecular relaxations, miscibility, and molecular interactions present in an amorphous polymer (PVPVA), a model drug (indomethacin, IND), and IND/PVPVA-based amorphous solid dispersions (ASDs). This is the first ever reported DMA study on PVPVA in its powder form, which avoids the contribution of solvent to the mechanical properties when a selfstanding polymer film is used. A good correlation between the techniques in determining the T-g value of PVPVA, IND, and IND/ PVPVA-based ASDs is established, and the negligible difference (within 10 degrees C) is attributed to the different material properties assessed in each technique. However, the overall T-g behavior, the decrease in T-g with increase in drug loading in ASDs, is universally observed in all the above-mentioned techniques, which reveals their complementarity. DMA and DRS techniques are used to study the different sub-T-g transitions present in PVPVA, amorphous IND, and IND/PVPVA-based ASDs because these transitions are normally too weak or too broad for mDSC to detect. For IND/PVPVA-based ASDs, both techniques show a shift of sub-T-g transitions (or secondary relaxation peaks) toward the high-temperature region from -140 to -45 degrees C. Thus, this paper outlines the usage of different solid-state characterization techniques in understanding the different molecular dynamics present in the polymer, drug, and their interactions in ASDs with the integrated information obtained from individual techniques.
KW  - amorphous solids
KW  - PVPVA
KW  - indomethacin
KW  - ASDs
KW  - dynamic mechanical
KW  - analysis
KW  - dielectric relaxation spectroscopy
KW  - sub-T-g relaxations
KW  - relaxation dynamics
Y1  - 2022
U6  - https://doi.org/10.1021/acs.molpharmaceut.2c00123
SN  - 1543-8384
SN  - 1543-8392
PB  - American Chemical Society
CY  - Washington
ER  -