Study growth kinetics in fluidized bed granulation with at-line FBRM

Model Based Estimation of 2D Crystallization Kinetics From Concentration and CLD Measurements

The Focused Beam Reflectance Measurement (FBRM) technique provides on-line and in-situ information about the chord length distribution of a population of particles in dispersion. This is rather promising for applications such as crystal size distribution control in crystallization processes. The objective of this study is to deepen the understanding of the characteristics of the FBRM measurement. On the one hand, a model is presented, which allows in principle to transform particle size distributions (PSD) into chord length distributions (CLD). On the other hand, measurements with particles in suspension show the critical dependence of the measurement on the optical properties of the system. A special technique has been developed to measure CLDs of single particles. These measurements clarify some of the above effects, detect possible over- and underestimations of particle size and give indications about how to interpret and exploit on-line CLD spectra.

The purpose of this study was to investigate effect of solvent type on solidification rate of ethyl cellulose(EC) microparticles and particle size/distribution of emulsion droplets/hardened microparticlesduring solvent evaporation process using focused beam reflectance measurement (FBRM). ECmicroparticles were prepared by an O/W-solvent evaporation method using various solvents, includingdichloromethane, dichloromethane:methanol (1:1), ethyl acetate and chloroform. The particle size/distribution of emulsion droplets/hardened microparticles was monitored by FBRM. The morphologyof EC microparticles was characterized by scanning electron microscopy (SEM). The transformationof emulsion droplets into solid microparticles for all solvents occured within the first 10-60 min. Thesquare weighted mean chord length of EC microparticles which were prepared using chloroform wassmallest, but the chord counts was no the highest. The chord length distribution (CLD) measured byFBRM showed that a larger particle size mean gave longer CLD and a lower peak of particle number.SEM data revealed that the morphology of microparticles was influenced by type of solvent. FBRMcan be employed for online monitoring of the shift in the microparticle CLD and detect transformationof emulsion droplets into solid microparticles during solvent evaporation process. The microparticleCLD and transformation process was strongly influenced by solvent type.Keywords: chord length distribution, ethyl cellulose, FBRM, microparticle, solvent.

Online ice crystal size measurements during sorbet freezing by means of the focused beam reflectance measurement (FBRM) technology. Influence of operating conditions

Polymorphs have a tendency to undergo solution-mediated transformation from one form to another during crystallization. Various in situ techniques explored for understanding the crystallization process include, Raman spectroscopy, near-infrared spectroscopy (NIR), and focused beam reflectance measurement (FBRM). Both Raman and NIR techniques are used for polymorphic identification. FBRM has gained much popularity as an ideal technique for studying and improving particle size. The crystallization process can be improved using FBRM by studying the meta-stable zone, temperature of crystallization, and primary and secondary nucleation. This FBRM technique offers a quick and time-saving approach along with insight on the particle size of the product. The same technique can be used during scale up to understand and monitor crystallization processes. This report describes a different application of FBRM, which involves monitoring the changes in chord length distribution as a result of polymorphic transformation associated with temperature during crystallization. Needle-shaped Form III of acitretin undergoes solvent-mediated transformation to cube-shaped Form II. This polymorphic transformation is monitored by monitoring the chord length distribution.

Chord length distributions measurements during crystallization and agglomeration of gas hydrate in a water-in-oil emulsion: Simulation and experimentation

The Focused Beam Reflectance Measurement (FBRM) technique provides on‐line and in situ information about the chord length distribution (CLD) of a population of particles in dispersion. The effect of changing the focal point position on the measured CLD is experimentally analyzed by carrying out single particle FBRM determinations in both pure water and a dispersion of fines. The results allow some general conclusions to be drawn about optimal focal point positions.

Dissolution of lithium carbonate (Li2CO3) in aqueous solution was investigated using three on‐line apparatuses: the concentration of Li2CO3was measured by electrical conductivity equipment; CLD (Chord Length Distribution) was monitored by FBRM (Focused Beam Reflectance Measurement); crystal image was observed by PVM (Particle Video Microscope). Results show dissolution rate goes up with a decrease of particle size, and with an increase in temperature; stirring speed causes little impact on dissolution; ultrasound facilitates dissolution obviously. The CLD evolution and crystal images of Li2CO3powders in stirred fluid were observed detailedly by FBRM and PVM during dissolution. Experimental data were fitted to Avrami model, through which the activation energy was found to be 34.35 kJ/mol. PBE (Population Balance Equation) and moment transform were introduced to calculate dissolution kinetics, obtaining correlation equations of particle size decreasing rate as a function of temperature and undersaturation. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Mixing energy as a scaling variable for liquid drawdown in stirred tanks

Validation of fluid bed granulation utilizing artificial neural network

The control objectives of batch crystallization processes are often defined in terms of particle size distribution (PSD), or properties related to the PSD, viz. average particle size, product filterability, dry solids flow properties, etc. To achieve these control objectives, a constrained nonlinear model-based optimization strategy has been adopted. This involves the detailed modeling of batch crystallization including model validation and parameter estimation, on-line monitoring of supersaturation and PSD, and the application of optimization strategies. A deterministic population balance model accounting for solution thermodynamics, crystal growth, and nucleation has been developed. State estimation is achieved by the on-line monitoring of temperature, concentrations in the liquid phase, particle density, and PSD. For this purpose, the focused beam reflectance measurement (FBRM) provides an on-line, in-situ information of crystal size and particle concentration in the form of a chord length distribution...

Development of an empirical method relating crystal size distributions and FBRM measurements

A novel wet milling-based automated direct nucleation control (WMADNC) concept is proposed and implemented in two continuous cooling crystallization processes in this work. In process 1, WMADNC is implemented upstream to provide closed-loop controlled primary nucleation kinetics and produce seed crystals in situ for continuous mixed suspension mixed product removal crystallizer (MSMPRC). In process 2, WMADNC is applied downstream to achieve closed-loop controlled secondary nucleation kinetics and reduce particle size for crystals in the MSMPRC through recycling. For both processes, a focused beam reflectance measurement (FBRM)-based closed-loop control approach is successfully implemented to control the nucleation kinetics inside the wet mill therefore to control the final chord length distribution (CLD). In the proposed WMADNC approach, the process critical quality attributes (CQA) (e.g., particle number or size) can be directly controlled by the automated closed-loop control framework, which on one hand...

Online monitoring lignocellulosic particles by focus beam reflectance measurement for efficient bioprocessing

A combined experimental and computational study of wet granulation in a Wurster fluid bed granulator