Accelerated Physical Stability Testing of Amorphous Dispersions.
The goal was to develop an accelerated physical stability testing method of amorphous dispersions. Water sorption is known to cause plasticization and may accelerate drug crystallization. In an earlier investigation, it was observed that both the increase in mobility and decrease in stability in amorphous dispersions was explained by the "plasticization" effect of water (Mehta et al. Mol. Pharmaceutics 2016, 13 (4), 1339-1346). In this work, the influence of water concentration (up to 1.8% w/w) on the correlation between mobility and crystallization in felodipine dispersions was investigated. With an increase in water content, the α-relaxation time as well as the time for 1% w/w felodipine crystallization decreased. The relaxation times of the systems, obtained with different water concentration, overlapped when the temperature was scaled (Tg/T). The temperature dependencies of the α-relaxation time as well as the crystallization time were unaffected by the water concentration. Thus, the value of the coupling coefficient, up to a water concentration of 1.8% w/w, was approximately constant. Based on these findings, the use of "water sorption" is proposed to build predictive models for crystallization in slow crystallizing dispersions.
Department of Pharmaceutics, University of Minnesota , Minneapolis, Minnesota 55455, United States.
Mehak
M
Mehta
Department of Pharmaceutics, University of Minnesota , Minneapolis, Minnesota 55455, United States.
Raj
R
Suryanarayanan
D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D058266:Dielectric Spectroscopy; D015736:Felodipine / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D014867:Water; D015736:Felodipine
PVP; coupling model; crystallization; dielectric spectroscopy; felodipine; molecular mobility; prediction; relative humidity; water