TY - JOUR
T1 - Crystallization Inhibition in Molecular Liquids by Polymers above the Overlap Concentration (c*)
T2 - Delay of the First Nucleation Event
AU - Song, Sichen
AU - Cui, Shuquan
AU - Sun, Changquan Calvin
AU - Lodge, Timothy P.
AU - Siegel, Ronald A
N1 - Publisher Copyright:
© 2024 American Pharmacists Association
PY - 2024
Y1 - 2024
N2 - Low concentration polymer additives can significantly alter crystal growth kinetics of molecular liquids and glasses. However, the effect of polymer concentration on nucleation kinetics remains poorly understood. Based on an experimentally determined first nucleation time (time to form the first critical nucleus, t0), we show that the polymer overlap concentration, c*, where polymer coils in the molecular liquid start to overlap with each other, is a critical polymer concentration for efficient inhibition of crystallization of a molecular liquid. The value of t0 is approximately equal to that of the neat molecular liquid when the polymer concentration, c, is below c*, but increases significantly when c > c*. This finding is relevant for effective polymer screening and performance prediction of engineered multicomponent amorphous materials, particularly pharmaceutical amorphous solid dispersions.
AB - Low concentration polymer additives can significantly alter crystal growth kinetics of molecular liquids and glasses. However, the effect of polymer concentration on nucleation kinetics remains poorly understood. Based on an experimentally determined first nucleation time (time to form the first critical nucleus, t0), we show that the polymer overlap concentration, c*, where polymer coils in the molecular liquid start to overlap with each other, is a critical polymer concentration for efficient inhibition of crystallization of a molecular liquid. The value of t0 is approximately equal to that of the neat molecular liquid when the polymer concentration, c, is below c*, but increases significantly when c > c*. This finding is relevant for effective polymer screening and performance prediction of engineered multicomponent amorphous materials, particularly pharmaceutical amorphous solid dispersions.
KW - Amorphous solid dispersion (ASD)
KW - Crystal growth
KW - Crystal nucleation
KW - Physical stability
KW - Polymer overlap concentration (c)
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U2 - 10.1016/j.xphs.2024.02.011
DO - 10.1016/j.xphs.2024.02.011
M3 - Article
C2 - 38369019
AN - SCOPUS:85186073864
SN - 0022-3549
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
ER -