Measuring induction times and crystal nucleation rates

Area of Science:

• Crystallization Science
• Physical Chemistry
• Materials Science

Background:

• Significant variability in crystallization induction times under identical conditions suggests a non-deterministic process.
• Experimental errors were ruled out, pointing towards inherent stochasticity in nucleation as the primary cause of variation.
• Understanding nucleation is critical for controlling crystal formation in various applications.

Purpose of the Study:

• To investigate the origins of large variations in induction times observed in 1 ml solutions.
• To accurately determine heterogeneous crystal nucleation rates for racemic diprophylline in two different solvents.
• To elucidate the role of solvent properties and energy barriers in the nucleation process.

Main Methods:

• Analysis of induction time distributions in 1 ml solutions of racemic diprophylline.
• Application of stochastic nucleation theory to explain observed induction time variations.
• Calculation of heterogeneous crystal nucleation rates and energy barriers in two distinct solvents.

Main Results:

• Induction time distributions are explained by the stochastic nature of nucleation, particularly when few nuclei form per vial.
• Accurate heterogeneous crystal nucleation rates were determined for diprophylline in two solvents.
• A significantly higher energy barrier for nucleation was observed in the solvent with longer induction times, indicating solvent-dependent nucleation behavior.

Conclusions:

• Stochastic nucleation is the dominant factor causing variability in crystallization induction times.
• Solvent properties critically influence the energy barrier for heterogeneous nucleation.
• Observed pre-exponential factors for nucleation rates are lower than predicted by Classical Nucleation Theory, suggesting limitations in current models or unknown particle characteristics.