Abstract
AbstractThe nucleation kinetics of the alpha form of p‐aminobenzoic acid from ethanolic and aqueous solutions is examined through a comparative examination of temperature‐jump and anti‐solvent drown‐out isothermal crystallization methodologies. Analysis of the data reveals the measured induction times, and the calculated effective interfacial tensions as a function of the supersaturation show broadly equivalent behavior for the aqueous‐ethanol mixed‐solvent drown‐out and temperature‐jump ethanol solution systems, confirming the comparability of the two methodologies. The results also demonstrate poorer agreement with the temperature‐jump pure aqueous system, highlighting the importance of the strength of solvation/desolvation as the key rate‐limiting process for the overall nucleation behavior.
Highlights
Isothermal by design (IbD) [1] is an antisolvent crystallization methodology for studying solution phase nucleation kinetics; it has been shown to be applicable over a wide range of supersaturations (S), accessing supersaturations that can be challenging to attain through conventional temperaturejump cooling-based isothermal crystallization methodologies
A comparison of two nucleation kinetic analysis routes was undertaken, with data collected from para-aminobenzoic acid (pABA) in mixed EtOH/ H2O solutions using IbD and data collected for both pABA in EtOH solutions and H2O solutions using temperature-jump isothermal methodology (TJM) compared with respect to supersaturation, induction time, effective interfacial tension, critical nucleus size, and number of molecules within the critical nucleus
Induction time data collected over a comparable range of supersaturation for IbD in mixed EtOH/H2O solutions and the TJM results for pABA in EtOH solutions showed a similar trend, with similar values of induction time
Summary
Isothermal by design (IbD) [1] is an antisolvent crystallization methodology for studying solution phase nucleation kinetics; it has been shown to be applicable over a wide range of supersaturations (S), accessing supersaturations that can be challenging to attain through conventional temperaturejump cooling-based isothermal crystallization methodologies. Whilst IbD has been shown to enable key nucleation kinetic information to be determined [1], such data has not, as of yet, been directly cross-correlated with those obtained by using temperature-jump isothermal methodology (TJM) for the same crystallization system. IbD utilizes an antisolvent methodology, whereby a miscible second solvent is added to a solution, which lowers the solubility of a given solute, increasing the level of supersaturation and the rate of nucleation (J), following the relationship J μ S. This relationship is outlined through the classical nucleation theory (CNT), which is the crystallization analysis pathway used in this study for IbD and TJM. The system choice of pABA from these solvent systems represents a well-studied model pharmaceutical compound used in many crystallization processes
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