Correlation Between Molecular Mobility and Crystal Growth of Amorphous Phenobarbital and Phenobarbital with Polyvinylpyrrolidone and L‐proline

The aim of the present study is to determine if the correlation between molecular mobility and crystallization growth rates exists over a broad temperature range from temperatures below the glass transition (Tg) to temperatures above the glass transition. Phenobarbital and solid dispersions of phenobarbital with PVP and L‐proline were studied in this research. Relaxation times below and above the Tg were measured. Crystallization was followed in a hot‐stage microscope and crystal growth rates were measured by observing radial growth of a single crystal. Arrhenius type temperature dependences were found both in relaxation times and crystal growth rates over studied temperature ranges, in all cases studied except in the case of pure phenobarbital, where a change of slope was observed for the crystal growth rate for the temperature range below Tg. For all cases, molecular mobility was correlated with crystal growth rate, for the temperature range studied, with a coupling coefficient of 0.38 for phenobarbital, and 0.23 and 0.28 for solid dispersions with PVP and proline respectively. By establishing the coupling between molecular mobility and crystal growth rate, predictive models can be created to estimate the stability of amorphous materials both, for pure form as well as for solid dispersions.