Crystallization Inhibition in Molecular Liquids by Polymers above the Overlap Concentration (c): Delay of the First Nucleation Event

• Published in: Journal of pharmaceutical sciences
• Main Authors: Song, Sichen, Cui, Shuquan, Sun, Changquan Calvin, Lodge, Timothy P., Siegel, Ronald A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.02.2024
• Subjects: Amorphous solid dispersion (ASD); Crystal growth; Crystal nucleation; Physical stability; Polymer overlap concentration (c); Crystal growth; Crystal nucleation; Polymer overlap concentration (c); Amorphous solid dispersion (ASD); Physical stability
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2024.02.011

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. [Display omitted]