Effect of Polymers on Crystallization in Glass-Forming Molecular Liquids: Equal Suppression of Nucleation and Growth and Master Curve for Prediction

Abstract

Crystal nucleation plays a critical role in the stability of supercooled liquids and glasses and is often controlled through addition of polymers. A dissolved polymer alters both the thermodynamics and the kinetics of nucleation, but the current understanding of these effects is limited. The rate of crystal nucleation has been measured in two molecular liquids, d-sorbitol and d-arabitol, containing polyvinylpyrrolidone (PVP) at different concentrations (0–15 wt %) and molecular weights (224 g/mol for the dimer up to 2 Mg/mol). We observe a significant inhibitory effect of PVP on crystal nucleation. Near the peak temperature for the nucleation rate (∼20 K above the glass transition temperature), 10 wt % PVP can slow down nucleation by approximately 1 order of magnitude, and the effect increases with polymer concentration exponentially and with molecular weight. Remarkably, the polymer effect on the nucleation rate is nearly the same as that on the crystal growth rate so that the ratio of the two rates is nearly constant at a given temperature independent of polymer concentration and molecular weight. This “master curve” behavior can be used to predict nucleation rates in multicomponent systems from more easily measured growth rates. It argues that nucleation and growth in these viscous liquids are both mobility-limited and that a polymer solute functions mainly as a mobility modifier, suppressing nucleation and growth to a similar degree.

Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

“…Polarized light microscope is one of the most widely used techniques in characterizing nucleation [21][22][23], crystal growth [24,25], polymorphic transition [26], and phase separation [27] of amorphous pharmaceutical solids. In recent studies, polarized light microscopy was often combined with a hot stage to extend its experimental temperature range and achieve the goal of precise temperature control.…”

“…Apart from studying crystal growth behaviors, polarized light microscope combined with hot stage can be used to explore the nucleation of amorphous pharmaceutical solids [21][22][23]. According to the different kinetics of nucleation and crystal growth, studies on drug nucleation can be mainly defined as one-stage method and two-stage method [21][22][23]. One-stage method can be used to determine the number of nucleation events per unit volume for the drug systems showing both fast nucleation and fast crystal growth behaviors.…”

“…In general, drug nucleation follows a steady rate after an induction period, followed by a slower rate due to the decreased available liquid volume for nucleation. Apart from studying crystal growth behaviors, polarized light microscope combined with hot stage can be used to explore the nucleation of amorphous pharmaceutical solids [21][22][23]. According to the different kinetics of nucleation and crystal growth, studies on drug nucleation can be mainly defined as one-stage method and two-stage method [21][22][23].…”

“…On the same scale of T/T g , nucleation rates of these four polyalcohols are vastly different, indicating the fundamentally different mechanisms of nucleation [21]. In a recent study, Yao et al compared the inhibitory effects of polymer on the crystal nucleation and growth via polarized light microscope combined with a hot stage [22]. Interestingly, the inhibitory effects of polymer on the crystal nucleation rates are similar to those on the crystal growth [22].…”

“…In a recent study, Yao et al compared the inhibitory effects of polymer on the crystal nucleation and growth via polarized light microscope combined with a hot stage [22]. Interestingly, the inhibitory effects of polymer on the crystal nucleation rates are similar to those on the crystal growth [22]. At a given temperature, the ratios between the rates of nucleation and growth are nearly identical, and are independent of the concentration and molecular weight of the polymer [22].…”