Metastable zone width for secondary nucleation and secondary nucleation inside the metastable zone

Abstract

Key words metastable zone width, interfacial free energy, nucleation, growth from solution.This study presents an evaluation of a new method, called zero growth activation free energy, used to determine the metastable zone width for the secondary nucleation case. It predicts the metastable zone width with a maximum error of 5-10%. Estimation of the metastable zone width for different isothermal crystallization conditions can be modeled according to a chosen reference set of growth experiments carried out in the volume diffusion regime at different initial supersaturations, using seed crystals of a certain characteristic size. Moreover, the activation free energy of the secondary nucleation was estimated. The role of the enthalpy of immersion in the formation of secondary nucleation events inside the metastable zone was pointed out, as well as its effect in causing extra-fast growth rate. Furthermore, sucrose crystal surface free energy was estimated.

Sucrose crystal growth in the presence of dextran of different molecular weights

“…The metastable zone width at 40 1C was experimentally found to be s¼[0À0.259] [18], so this work was carried out within the metastable zone range for this temperature. Size distribution analyses of the final crystals were performed for the runs containing concentrations of dextran equal to 3.85 g/L of water at 50 1C (see Fig.…”

“…Overall linear growth rates R, R i (m/s) were calculated using a 1 ¼0.64 and b 1 ¼4.52, and applying the same growth rate formula as shown in other work [18]. Growth rate curves were represented as R vs. s or R i vs. s.…”

Oscillatory Flow Reactors (OFRs) for Continuous Manufacturing and Crystallization

“…100 -500 µm), high quality crystals, which can be reproduced consistently, are typically desired for industrial crystallization processes. Several factors contribute to the final CSD including primary 27 and secondary 28 nucleation, growth, agglomeration, attrition and crystal breakage, encrustation, disturbances to the metastable zone width (MSZW, 26,27,29 see Figure 1) such as an impurity profile, polymorphism, agglomeration/aggregation, solvates and hydrates and seeding. Conventional approaches for obtaining crystals of a desired crystal form and size distribution have suffered from batch-to-batch variability, particularly at the manufacturing scale.…”

“…For example, the crystal size distribution (CSD) is commonly used as a critical quality attribute (CQA), and relatively large (e.g., 100–500 μm), high quality crystals, which can be reproduced consistently, are typically desired for industrial crystallization processes. Several factors contribute to the final CSD, including primary and secondary nucleation, growth, agglomeration, attrition and crystal breakage, encrustation, and disturbances to the metastable zone width (MSZW, ,, see Figure ), such as an impurity profile, polymorphism, agglomeration/aggregation, solvates, and hydrates and seeding.…”

A perspective on the growth-only zone, the secondary nucleation threshold and crystal size distribution in solution crystallisation

“…It has also been investigated in connection with lysozyme crystallisation. 17 Khaddour and Rocha 18 have investigated 'secondary nucleation within the metastable zone', which is presumably the same phenomenon, but have not considered it in relation to product formation. The terms 'surface secondary nucleation', 'activated secondary nucleation' and 'surface-activated secondary nucleation' have been used by Puel, Veesler and coworkers [19][20][21] to describe what appears to be the onset of the same boundary.…”