Predicting Crystallization of Amorphous Drugs with Terahertz Spectroscopy

TY - JOUR

T1 - Predicting Crystallization of Amorphous Drugs with Terahertz Spectroscopy

AU - Sibik, Juraj

AU - Löbmann, Korbinian

AU - Rades, Thomas

AU - Zeitler, J Axel

PY - 2015/8/3

Y1 - 2015/8/3

N2 - There is a controversy about the extent to which the primary and secondary dielectric relaxations influence the crystallization of amorphous organic compounds below the glass transition temperature. Recent studies also point to the importance of fast molecular dynamics on picosecond-to-nanosecond time scales with respect to the glass stability. In the present study we provide terahertz spectroscopy evidence on the crystallization of amorphous naproxen well below its glass transition temperature and confirm the direct role of Johari–Goldstein (JG) secondary relaxation as a facilitator of the crystallization. We determine the onset temperature Tβ above which the JG relaxation contributes to the fast molecular dynamics and analytically quantify the level of this contribution. We then show there is a strong correlation between the increase in the fast molecular dynamics and onset of crystallization in several chosen amorphous drugs. We believe that this technique has immediate applications to quantify the stability of amorphous drug materials.

AB - There is a controversy about the extent to which the primary and secondary dielectric relaxations influence the crystallization of amorphous organic compounds below the glass transition temperature. Recent studies also point to the importance of fast molecular dynamics on picosecond-to-nanosecond time scales with respect to the glass stability. In the present study we provide terahertz spectroscopy evidence on the crystallization of amorphous naproxen well below its glass transition temperature and confirm the direct role of Johari–Goldstein (JG) secondary relaxation as a facilitator of the crystallization. We determine the onset temperature Tβ above which the JG relaxation contributes to the fast molecular dynamics and analytically quantify the level of this contribution. We then show there is a strong correlation between the increase in the fast molecular dynamics and onset of crystallization in several chosen amorphous drugs. We believe that this technique has immediate applications to quantify the stability of amorphous drug materials.

U2 - 10.1021/acs.molpharmaceut.5b00330

DO - 10.1021/acs.molpharmaceut.5b00330

M3 - Journal article

C2 - 26090554

SN - 1543-8384

VL - 12

SP - 3062

EP - 3068

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

IS - 8

ER -