Estimation of Nucleation and Growth Kinetics of Benzoic Acid by Population Balance Modeling of a Continuous Cooling Mixed Suspension, Mixed Product Removal Crystallizer

Abstract

Nucleation and growth kinetics of benzoic acid crystallized by cooling from 1.5:1 (w/w) water/ethanol solutions were determined using a 500 mL continuous mixed suspension, mixed product removal (MSMPR) crystallizer and a mathematical model of the MSMPR process. The developed model solves the population, moment, and mass balance relationships with the kinetic expressions for the system and is coupled with a nonlinear optimization routine for kinetic parameter estimation. Comprehensive experimental data for model fitting and parameter estimation was obtained by varying crystallizer operating conditions to induce changes in the rate-affecting variables for growth and nucleation (temperature, supersaturation, and suspension density). The size distribution was monitored in real-time using focused beam reflectance measurement (FBRM) to identify steady-state and hence to enable on-demand adjustment of the operating conditions to transition multiple steady-states for rapid acquisition of kinetic data. A Malvern Mastersizer was used to quantify the crystal size distribution (CSD) at steady-state, whereas concentration was determined gravimetrically. Six kinetic parameters for crystal growth and nucleation were estimated from the model fitting procedure, which enabled accurate prediction of CSD and concentration results at steady-state.

Diastereomeric salt crystallization of chiral molecules via sequential coupled‐Batch operation

“…In the present work, the ternary phase diagram (TPD) is used to resolve pure diastereomeric salts of ibuprofen lysine by batch crystallization via both sequential batch and sequential coupled batch crystallization; the performance of these two approaches are analyzed and compared. Systematic application of in situ process analytical technologies has been of significant benefit development of novel batch and continuous crystallization methodologies . This article expands this approach to track the progression of sequential, and sequential coupled‐batch diastereomeric resolution, with offline chiral high‐performance liquid chromatography (HPLC) used to quantify enantiomeric purity with a high degree of accuracy.…”

Thermo‐Kinetic Investigation of the Preparation of Micronized Ammonium Perchlorate Particles by Using Rapid Cooling Crystallization Method

“…As mentioned in anti-solvent research [7], with respect to performed design, the value of mixing has a direct relation with pressure. In a research performed by Lakshmi et al, the value of mixing has been measured by solution stirring to produce AP [43,44]. The influence of mixing rate on crystal size in rapid cooling method was obtained 0.1 μm/rpm.…”

Design of a Combined Modular and 3D-Printed Falling Film Solution Layer Crystallizer for Intermediate Purification in Continuous Production of Pharmaceuticals

“… 21 Continuous stirred tank reactors (CSTRs), mixed suspension mixed product removal (MSMPR) crystallizers, and tubular and oscillatory flow crystallizers have been demonstrated to be able to monitor, characterize, model, and control all important crystal product attributes for pharmaceuticals such as crystal size distribution (CSD), 2 , 13 , 14 , 22 − 25 morphology, 13 , 14 , 22 chemical purity, 11 , 12 , 26 yield, 11 , 12 , 26 , 27 chirality, 28 or polymorphic purity. 28 − 32 …”