Denis Mangin

Kinetics identification of salicylic acid precipitation through experiments in a batch stirred vessel and a T-mixer

This work aims to identify the mechanisms and kinetics of salicylic acid precipitation. A large supersaturation domain is covered (initial supersaturation ratios between 2.7 and 65.0) and two experimental set-ups are used. At low supersaturations, precipitations are performed in a stirred vessel, whereas a T-mixer must be used at high supersaturations in order to avoid hydrodynamic effects. In each case, the precipitation mechanisms actually involved are different and their kinetics are identified by solving the population balance with the method of classes. Thus, at low supersaturations in the stirred vessel, the primary nucleation is of heterogeneous type and the secondary nucleation is dominant, whereas homogeneous primary nucleation dominates in the T-mixer at high supersaturations. The crystal growth is diffusion controlled in the stirred vessel and turns into an integration limited mechanism in the T-mixer.

Agglomeration in suspension of salicylic acid fine particles: influence of some process parameters on kinetics and agglomerate final size

Abstract Agglomeration in suspension is a size-enlargement method that facilitates operations of solid processing (filtration, transport, galenic) and preserves the solubilization properties of fine particles. It consists in adding to a suspension of microparticles a small quantity of a second liquid acting as an interparticle binder; in a suitably agitated equipment with a critical quantity of binder, spherical and dense agglomerates of a few millimeters in diameter may be formed. This paper presents a new methodology to study the agglomeration process. The system [salicylic acid/aqueous solution/chloroform] is chosen as a model system. To follow in situ the agglomerate formation and growth, an original device based on image acquisition and analysis is developed; agglomerate porosity and compressive strength are also measured. These measurements allow us to identify the influence of the process parameters on the agglomeration kinetics, the size and the compressive strength of the final agglomerates. They also give interesting insights into the mechanisms.

Modelling gibbsite agglomeration in a constant supersaturation crystallizer

An important stage of the Bayer process leads to the formation of gibbsite particles (Al(OH)3) mostly grown by agglomeration (aggregation and crystal growth). In this work, a population balance model is developed to account for experimental data generated in a constant supersaturation crystallizer. The objective is to quantify the effect of the seed concentration on the agglomeration kinetics. The population balance equation is discretized and solved with the method of classes. Several classical agglomeration and fragmentation kernels are tested. The size-independent agglomeration kernel taken alone results in the most suitable description of the experiments. The kinetic constant must then strongly decrease with the seed mass. The hypothesis of an agglomeration kernel independent of the seed mass combined with a fragmentation kernel increasing with the seed mass is also tested. Results are compared and discussed with the previous ones drawn from the literature.

Precipitation and adsorption during fluoride removal from water by calcite in the presence of acetic acid

ABSTRACTDefluoridation of groundwater is of major concern in several places around the world, such as North and East Africa, India and China. In this paper, removal of fluoride from model solutions and a Tunisian groundwater sample was performed using calcite particles in the presence of acetic acid in batch experiments. After 1 h decantation, dead-end microfiltration was further used to retain the fluorite (CaF2) precipitates present in the supernatant. At 5 mg L−1 fluoride concentration, removal efficiency was found to increase from 17.4% without acid to 30.4% with 0.1 M acetic acid. The increase in fluoride removal with acetic acid was mainly attributed to the renewal of the area available for adsorption on the calcite particles. At the fluoride concentration of 50 mg L−1, the removal efficiency was equal to 9.5% without acid and 94.3% with the addition of 0.1 M acetic acid. The removal of fluoride was attributed to precipitation as a result of higher supersaturation in the solution. Optimum parameters...

Chapter 9:Co-crystallization in Solution and Scale-up Issues

This chapter focuses on the co-crystallization process in organic compounds. The operation is performed in batch mode in order to meet regulatory requirements. The industrial manufacturing process is carried out in solution for economical reasons. When a co-crystal form is chosen from among the different screened solid forms of an API, the development of such a co-crystallization process starts on the lab scale in a thermostated mechanically stirred reactor, since it is representative of the most popular apparatus used in the chemical and pharmaceutical industry. We recall that the nucleation, growth and dissolution mechanisms involved in the crystallization of a mono-component crystal are similarly acting in the co-crystallization of a multi-component crystal. The development process starts after co-crystal screening with the construction of a thermodynamic phase diagram of the system API/co-crystallizing agent/solvent. The definition of the operating conditions requires taking into account the possible kinetic pathway in the phase diagram during the run since other solid forms (single component crystal or another co-crystal form) may appear and compete against the co-crystal form. Several solid phases may appear concomitantly or consecutively during the process, some of them may disappear whereas others continue to grow. The choice of a “safe” operating region combined with a seeding strategy ensures the presence and development of only the desired co-crystal form all along the run. However in the case of a final co-crystal phase mixed with another crystalline phase due to a process deviation, it is possible to trigger a solution-mediated phase transition in suspension by manipulating the concentration of one of the co-crystal components, in order to suppress this unexpected solid phase and to fulfill the crystalline purity requirements.

Precipitation of Microcrystals of Salicylic Acid in a T Mixer: Experimental Study and Modelling

Precipitations of salicylic acid with high initial supersaturation ratios (27–46) are performed in a T mixer in order to avoid mixing effects. The model assimilates the T mixer to a perfectly mixed reactor followed by a perfect plug flow reactor. Primary nucleation and growth kinetics are quantified. The results are compared with those obtained in a previous work at lower supersaturations.