On the interpretation of metastable zone width in anti‐solvent crystallization

Abstract

Considering nonlinear dependence of solute concentration on anti-solvent−solvent composition a modified Nývlt-like equation based on traditional power-law relation between nucleation rate and developing supersaturation and a new equation based on the classical theory of three-dimension nucleation are proposed to explain the dependence of anti-solvent addition rate on metastable zone width defined as excessive antisolvent composition in anti-solvent crystallization. The experimental data on the metastable zone width in anti-solvent crystallization of benzoic acid are analyzed and discussed from the standpoint of these equations. It is found that the new approach based on the classical nucleation theory provides better insight into the processes involved in anti-solvent crystallization. Analysis of the experimental results on anti-solvent crystallization of benzoic acid [D. O'Grady, M. Barret, E. Casey, and B. Glennon, Trans. IChemE A 85, 945, (2007)] revealed that: (1) the value of metastable zone width for a solvent−anti-solvent system is determined by the solute−solvent and solute−anti-solvent interactions, (2) the dependence of the metastable zone width on stirring is associated with the enthalpy of mixing, and (3) the new approach predicts a threshold antisolvent addition rate associated with the setting up of an equilibrium between solvent and anti-solvent and a maximum anti-solvent addition rate connected with the induction period t ind for the onset of crystallization.

Total Synthesis of (–)‐Isoamericanin A and (+)‐Isoamericanol A

“…The nucleation kinetic parameters were estimated from the MSZW data obtained for the case when the anti‐solvent was added close to the impeller (sufficient mixing), using the classical nucleation theory of Nyvlt 25, with modification for anti‐solvent addition rather than cooling 7, 18–20. The nucleation rate ( J ) can be expressed by the empirical power‐law relation …”

“…The MSZW is defined as an excessive anti‐solvent composition or supersaturation at which the number density of accumulated grown primary nuclei reaches a specified value when the anti‐solvent is added continuously with a given flow rate and the steady‐state primary nucleation in the bulk solution is assumed to be achieved instantaneously at any time. Sangwal 19 proposed a new Nyvlt‐like equation based on the traditional power‐law relation between the nucleation rate and supersaturation, to capture the nonlinear dependence of the solute concentration on the anti‐solvent/solvent composition. The author also proposed a new equation based on the classical theory of three‐dimensional nucleation and analyzed the behavior of the benzoic acid system from the standpoint of these equations.…”

A novel membrane distillation response technology for nucleation detection, metastable zone width measurement and analysis

“…In addition, the membrane distillation technology was also reported as the antisolvent addition devices (Drioli et al, 2012;Profio et al, 2010), and well-designed interpretation model of antisolvent crystallization was also proposed (Mostafa Nowee et al, 2008;Sangwal, 2010), which explored a potential application of the MDR technology to the MSZW of antisolvent crystallization process.…”

“…Thus, the supersaturation variation rate is the key model parameter of the theoretical models of the MSZW measured by the classic ploythermal method (cooling rate R¼ dT/dt) and the MSZW measured by the membrane concentrated method (concentrating rate R 0 ¼ dC=dt). Theoretical approaches proposed by Sangwal (2010); Sangwal et al (2014) are employed to analyze the MSZW measured by the classic ploythermal method. In the concentration range that nucleation occurs, the supersaturation is related with the metastable zone width by the approximate linear dependence.…”

The influence of solution environment on the nucleation kinetics and crystallisability of para-aminobenzoic acid

“…This method relates Tc to the cooling rate, q, to calculate nucleation kinetics and information about crystallite growth. The most common interpretation of Tc vs q data is using the empirical Nyvlt expressions 17 , 18 , however Kubota 19 and Sangwal 20,21 have recently re-interpreted these equations in order to derive more physically meaningful parameters. These poly-thermal approaches have been comprehensively reviewed and applied to paracetamol-ethanol solutions by Mitchell et al through which the key kinetic parameters were derived 22 .…”