Nucleation, Growth, and Pseudo-Polymorphic Behavior of Citric Acid As Monitored in Situ by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy

The crystallization, dissolution, and associated pseudo-polymorphic behavior of citric acid crystals from aqueous solution is investigated using temperature-programmed and isothermal batch experiments. Quantitative attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy is used to measure in situ the solution concentration and hence the reactant supersaturation over a wide range of solution undercoolings within the metastable zone. Detailed mapping out of the solubility−supersolubility diagram reveals poor nucleation behavior as characterized by a very wide metastable zone width (typical value, 55 °C for a cooling rate of 0.05 K/min). Simultaneous ATR FTIR and optical turbidometric measurements are used to cross-correlate the supersaturation driving force to the nucleation behavior as followed prior to and during crystallization within the metastable zone. Both temperature-programmed and isothermal measurements reveal behavior consistent with spontaneous liquid-phase separation within the highly supersaturated mother liquor prior to crystallization, the occurrence of which is known as oiling-out, a phenomenon poorly understood in industrial crystallization reactions. Parallel examination of the phase of the product crystals, using in situ and ex situ powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC), reveals the formation of the anhydrous form of citric acid via temperature-programmed experiments and the monohydrate phase being crystallized via isothermal experiments. These results, which correlate with the solubility−supersolubility phase diagram, are rationalized in terms of the respective crystal chemistry of the anhydrate and monohydrate structures of citric acid, which is consistent with a solvent-mediated phase transformation mechanism effecting the change from the anhydrate to the monohydrate form.