A population balance model of the solution‐mediated phase transition of citric acid

Abstract

International audienceThe Solvent-Mediated Anhydrous to Monohydrate Phase Transition (SMPT) of citric acid in water was monitored using in situ Raman spectroscopy and image analysis. The solid phase composition, solute concentration, and crystal size distribution were measured during experiments designed to investigate the different steps of the SMPT process: dissolution of the metastable form, nucleation, and growth of the stable form. A Population Balance Model (PBE) was developed to depict the time evolutions of the two populations of particles involved. Nucleation and growth phenomena were analyzed and described through simplified kinetic laws. The related kinetic parameters were estimated through the nonlinear least squares minimization of model-experiments prediction errors. The overall PBE model was finally found to satisfactorily describe the SMTP process; the time variations of the solute concentration and solid phase composition in particular. It is clearly shown that the secondary nucleation of stable monohydrate particles depends on both the supersaturation anti the overall solid content. Surprisingly, as far as the nucleation of stable particles in the presence of metastable solid is concerned, the rate of particle generation was found to exhibit identical dependency on the metastable and stable content, a feature which remains to be further investigated and explained

Comparison between approaches for the experimental determination of metastable zone width: A case study of the batch cooling crystallization of ammonium oxalate in water

“…Aiming at obtaining partial information on the nucleation kinetics, many different methods have been reported in the literature [1][2][3][4][5][6][7][8]. The formation of a new solid phase can be detected in several different ways, for example, through the appearance of crystals or through changes of the solution properties (turbidity, refractive index) [9][10][11].…”

Acoustic emission during the solvent mediated cooling crystallization of citric acid

“…The latter phenomena were simulated using Population Balance Equation (PBE) model and in situ Raman measurements of the solute concentration C(t). A previous monitoring and modelling study of the system under investigation was reported by [26]. Such simulation, even though it is not explicitly used here, allows understanding the main features of the solute concentration trajectory with respect to phase transition events.…”

Raman Spectroscopy

“…Examples of solvent -mediated transformation monitoring include the conversion of anhydrous citric acid to the monohydrate form in water [235,236] , CBZ with water [237] and ethanol -water mixtures [238,239] , and cocrystallization studies of CBZ, caffeine, and theophylline with water [240] . Raman spectroscopy was used to monitor the crystallization rate and solute and solvent concentrations as griseofulvin was removed from an acetone solution using supercritical CO 2 as an antisolvent [241] .…”