ARR - Annual Report
Nanotechnology applications in the pharmaceutical, materials and chemical industries has renewed interest in the use of wet grinding in stirred media mills for the production of nanoparticles. However, challenges arise in the production of sub-micron particles that are, in part, due to colloidal surface forces influencing slurry stability and rheology. As often observed in the literature, a grinding limit in the range of 0.5 µm is reached despite high energy inputs and aggressive milling conditions. Furthermore, the product size can even increase with increased energy input, a seemingly counterintuitive result that is attributed to aggregation of fine particles during the milling process. By producing particles smaller than a median particle size of 1 µm a steady state between breakage and agglomeration exists in the milling process. This equilibrium is controlled by interparticle interactions as well as the milling conditions. In this report we demonstrate that this steady state particle size is independent of the feed particle size and can be reached by agglomeration of small particles as well as by real breakage of large particles.
Furthermore, we extended our studies to non-aqueous systems, because of the high industrial demand on nano particles in organic solvents. Milling studies with steric and electrostatic stabilization showed that the size of the particles milled in organic solvents is conspicuously smaller than the size of the particles milled under the same conditions in the aqueous phase. However, ions dissolved from the media wear and impurities in the suspension can destabilize the suspensions if the electro-static stabilization mechanism is chosen. This is not the case for steric stabilized systems.
An important question is whether the mechano-chemical activation which was observed in aqueous media is crucial to obtain nano-particles. Differential Scanning Calorimetry (DSC) and X-ray difraction (XRD) measurements showed no mechano-chemical changes during milling in ethanol and toluene. In the aqueous phase the stabilization mechanism has no influence on the amount of hydroxide phase. A protecting polymer cover around the particles does not prohibit the mechano-chemical changes.
The present research is oriented towards the grand challenge to understand general powder dynamics and the ultimate goal of the work is to develop a quantitative description of active flows of fine powders. The study is centered on the “intermediate” regime of flow where both frictional and inertial effects are important and where fluctuations of strain rate and stress are significant. The main application is in the area of small-size, rough and/or cohesive powders that are industrially relevant. The novelty of the project is to study a relatively large range of materials and flow geometries to gain meaningful insight as opposed to limiting the work to a single “relevant” flow device using a “standard” powder. Extensive previous work mainly in the Physics literature on smooth glass beads and hard, metal spheres have done little to shed light on the behavior of industrially important powders that are usually non-spherical, rough, fine, cohesive and compressible.
We report on a series of materials from simple (round beds) to complex (fine, odd-shaped and slightly cohesive), used in a set of judiciously chosen equipment with interchangeable boundary conditions and measure stresses and stress fluctuations as a function of geometry and shear rate. The goal is to develop constitutive equations for powder flows and to use them in continuum-type theoretical models to predict flow patterns, velocity distributions and forces on boundaries such as stationary walls and moving pedals.
The approach follows the earlier work of Tardos, (1997), Tardos et al., (2003), and Tardos and Mort, (2005) and applies it to the geometry of the Couette device and to more complex flows such as hopper (funnel) and centripetal (“spheronizer” and high-shear mixer) flows that are relevant to storing, feeding, mixing and granulating powders.
This project has an overall goal of designing model-based control algorithms using multi-scale descriptions of particle attributes in high-medium shear granulators. The first objective of the second year of this project was to design a reduced order model that is appropriate for real time applications. The second objective involved a feasibility study of applying a reduced order model in a Model Predictive Control (MPC) algorithm. The methods used to reach these objectives have prepared us for the next stage, the objective for the third year: application of MPC algorithms on a pilot plant granulator. During the scope of this project four different granulation models have been considered (in order of complexity):
- Transfer function model (Pottmann, et al., 2000; Gatzke and Doyle, 2001)
- One dimensional well mixed discretized Population Balance Model (PBM) (Sanders, et al., 2005)
- One dimensional three compartment discretized PBM (Wang, et al., 2006)
- Three dimensional PBM (Immanuel and Doyle, 2005)
The models were either used as a plant model to simulate a real plant or as the basis for a linear controller model. This report described the details of the research with the second model. The fourth model has been described in our first year report (IFPRI # ARR51-01). The third model has been developed by the group in Queensland and had been adjusted to model their pilot plant, which will be used in future studies in this project. The main differences between model 2 and model 4 are the recycle flow (+ screens and crusher) and the introduction of three separate regimes in the granulator. More details about the UQ model and pilot plant are described in section 6: Summary and Future Work.
Abstract
The first part of this report (Chapter 3 and 4) present the framework that was used to setup and test an MPC controller on a simulated plant model. The plant model is based on earlier work done at The University of Sheffield and Organon, The Netherlands (Sanders, et al., 2005). The granulation kinetics were measured in a 10 liter batch granulator with an experimental design that included four process variables. The aggregation rates were extracted with a Discretized Population Balance model. Knowledge of the kinetics was used to model a continuous (well mixed) granulator. The controller model is a linearized state space model, derived from the nonlinear DPB model. It has the four process variables from the experimental design and a feed ratio as input variables. Since the DPB model describes the whole size distribution (GSD), different sets of output variables were chosen and compared. Preliminary results show successful implementation of Model Predictive Control on a continuous granulator. Further research is needed to test the linear model on an actual pilot plant.
Funding for this project has only commenced 10 days ago, as such no results are presented in this report. A brief report is presented of the preparations that have taken place. This primarily involves the acquisition of appropriate materials for the study.
The aim of this project is to enhance our understanding of how solvents and supersaturation affect the nucleation of polymorphic forms of compounds. Polymorphism is very important to the pharmaceutical industry as a compound’s polymorph can exhibit different physical properties, some more desirable than others. Being able to control which polymorphic form is nucleated is thus very important. In the first year of this project, the dimorphic enantiotropic compound p-aminobenzoic acid was selected as the model compound due to the availability of its solubility data and the relatively low transition temperature between its and polymorphs. The second year of the project has been focused on the precise location of the transition temperature and measuring the relative nucleation rates of and at different temperatures.
Background
Research background
There have been few studies of the relative nucleation rates of two polymorphic forms. Figure 1 shows a schematic phase diagram for an enantiomorphic system of Polymorphs I and II, it is characterised by a transition temperature at which the relative solubility and hence stability of forms switches. At the transition temperature
EXECUTIVE SUMMARY
The aim of the project is to establish a relationship between the product properties and feed material and the mill functions for milling of organic solids. The specific objectives are:
- a) To characterise the physical, mechanical, and thermal properties of organic feed materials (material function) at the single particle level, and to examine the effects of temperature and humidity on these properties,
- b) To investigate the breakage behaviour of single organic particles at quasi-static and dynamic conditions under the influence of temperature and humidity,
- c) To investigate the bulk milling behaviour of model organic solids and mill hydrodynamics (mill function),
- d) To characterise the properties of milled product, and to correlate the product properties to material and mill functions.
Model materials planned and approved for use in the project by the TC of IFPRI include aspirin, á -lactose monohydrate, sucrose or sorbitol, starch, and microcrystalline cellulose. These materials cover a fairly wide range of physical, mechanical and thermal properties, hence ensuring generality of the results to be achieved. This report summarises the work done over the second year of the project. The work includes the single particle breakage studies using the impact tester under both ambient and sub-ambient conditions, surface characterisation of the product particles using the Dynamic Vapour Sortion (DVS) device, measurements of Young’s modulus and hardness of single aspirin crystals using the nano-indentation method, analysis of the bulk milling behaviour of aspirin under both ambient and sub-ambient conditions, analysis of the mill dynamics, the use of a flow aid Aerosil to prevent re-agglomeration of milled products during the bulk milling, and population balance modeling of the milling of aspirin in collaboration with Du Pont. An attempt has also been made to relate the characteristics of the milled products in terms of particle size to the properties of feed material - the primary aim of the research. The single particle impact tests at the ambient conditions show that data on the breakage extent fit well to the model developed by Ghadiri and Zhang (2002) for semi-brittle materials. The aspirin particles used in this work are non-spherical but very close to the cubic shape. High speed digital video recording suggests that aspirin particles impact on the target from edges/corners of the particles. SEM analysis of particles after the impact testing shows that the failed surfaces under the ambient conditions are fairly smooth, suggesting possibility of particle failure at the cleavage planes. A reduction in temperature has a marked effect on the single particle breakage behaviour of aspirin. The new surfaces at the sub-ambient conditions are rougher than that in the ambient conditions, suggesting that the particle failure may be not at the cleavage planes under the sub-ambient conditions.
Fine and ultra-fine grinding is of great interest to many industries. Examples of applications are fillers for paper and plastic coatings, pigments, ceramics for abrasive and structural applications, toners for photocopy and printing machines. Besides the direct synthesis of these materials by chemical methods, wet grinding in stirred media mills is a suitable method for the production of sub-micron particles. In the sub-micron size range the behaviour of the product suspension is more and more influenced by increasing particle-particle interactions. Due to these interactions, often spontaneous agglomeration of product particles occurs and the viscosity of the product suspension increases [1] [2]. To overcome this problem the milling suspension has to be stabilized by means of electrostatic, steric or electrosteric stabilization.
In this study, milling of electrostatically stabilized alumina particles in water, sterically stabilized alumina particles in water and ethanol has been accomplished. Preliminary to the milling experiments of sterically stabilized alumina particles in different media, adsorption isotherms of the polymer DAPRAL GE 202 on alumina particles in water, ethanol, 2-butanol and toluene has been explored. These adsorption isotherm curves show that the amount of adsorbed polymer on the surface of the alumina particles in 2-butanol is higher than in ethanol, water and toluene. This indicates that the affinity and conformations of the hydrophobic and hydrophilic parts of the polymer chains are oriented differently according to the nature of the solvents.
The median particle sizes of the milled product particles of sterically stabilized alumina in ethanol is less than the milled product particles of sterically stabilized and electrostatically stabilized alumina F-320 particles in water at the same milling conditions. This is supported by different measuring techniques like DLS, SEM and BET. SEM pictures show a particle size of 50 nm for the milled sterically stabilized particles in ethanol. Mechanochemical changes from alumina to alumina hydroxide have been observed during wet grinding of sterically and electrostatically stabilized particles in water. The amount of the hydroxide phase is the same regardless of the stabilization method. This point is supported by characterizing sample with the DSC method.
In contrast to milling experiments with alumina particles in water no mechanochemical changes occur for sterically stabilized alumina milled in ethanol. In this system the obtained median particle sizes are the result of pure mechanical grinding, because the formation and dissolving of an hydroxide layer is not observed. This fact is supported by different characterizing methods like XRD, DSC and FTIR analyses. And also in this study with the help of Whole Powder Pattern Modelling, the microstructural study of the materials based on the analysis of the X-ray diffraction patterns of the milled samples has been carried out. The particles are breaking at the interface of the crystallites leading to smaller particles until a critical domain size is reached, which we believe is the real grinding limit.
In case of tin oxide the critical domain size or grinding limit is reached at 2 nm. Whereas, the critical domain size of tin oxide obtained from Rietveld and Scherrer methods are 5 and 15 nanometers.
IFPRI Research on Attractive Colloids and Gelling Systems
IFPRI members have selected ‘attractive colloids and gelling systems’ as a possible priority topic within the general area of ‘wet systems’. As a start, a small one-year project was set up, in which 6 leading research groups accepted to collaborate in order to explore/demonstrate the potential, as well as possible routes, for IFPRI research in this domain. Here, the groups report their contributions with experiments on common model systems which where specifically prepared for this project.
The results demonstrate that a wide range of experimental techniques is available that can be applied to gelling systems. Various rheological techniques have been used; they can be applied to all kinds of industrial systems. Other techniques probe the structure and the dynamics of the particles. Some of them operate time-resolved and/or during flow. They include e.g. confocal microscopy and scattering techniques (here light and X-rays have been used), these can be applied during flow. Also micromechanical tools are available, using e.g. optical tweezers.
One of the groups put the results in a theoretical perspective, pointing out how such data could provide a basis for further theoretical modelling of gelling systems. On the basis of the results it can be concluded that IFPRI-stimulated research in this area could provide industrially relevant results at this stage.
This report presents the results of a ten month ongoing research on 3D size and shape characterization of particles. This work has been performed at the GeMMe Laboratory under the responsibility of Prof. Eric Pirard and was supported by a research grant from the International Fine Particle Research Institute. This research has two main aspects, firstly reviewing and validating the existing 3D imaging techniques and secondly developing 3D dedicated image analysis and 3D dedicated size and shape parameters.
3D Imaging Techniques
The first part is dedicated to 3D imaging techniques. A set of powder samples with different physical properties was gathered and tested on three optical imaging techniques and two imaging techniques based respectively on x-ray and electron beams.
- The structured lighting is an optical imager based on the Moiré principle.
- The infinite focus is a reflected light microscope coupled with a digital image processing taking advantage of the finite depth of focus.
- The confocal microscope is based on laser reflection and is also associated with a digital image processing.
All three techniques are surfometric imaging instruments giving the elevation for the entire image. X-ray and electron tomography are imaging from sections techniques. Their scales of investigation are respectively micrometric and nanometric. The advantages and drawbacks of each 3D imaging technique were enumerated regarding particle characterization specifications.
3D Image Analysis and Measurement
The second part of the report is about 3D image analysis and measurement. Programs were implemented to compute size and shape parameters of individual particles. At this stage of the research, volume, surface area, sieve diameter, aspect ratios and convexity index can be calculated for a particle. All the programs were validated on synthetic particles for which the geometry is completely known. Then, they were tested on 3D images of real powder samples obtained from x-ray and electron tomographies.
Ongoing Researches
The last part presents the ongoing researches with intermediate results and the perspectives for the short and medium terms.
The objective of this third year was to collect data from a pilot plant for control testing. A team of 4 visiting researchers joined the existing particle research group in Queensland (Jim Litster, Ian Cameron, Fu Yang Wang, David Page, Rachel Smith) for an experimental campaign: Jonathan Poon and Rohit Ramachandran, both PhD students at Imperial College London, supervised by Charles Immanuel; Thomas Glaser a diplomarbeit student from Stuttgart who stayed in Frank Doyle's group in Santa Barbara for a year; and Constantijn Sanders a post doc in the Doyle group. Thomas recently graduated and Jonathan is writing up his PhD thesis.
The team had 2 objectives while in Queensland:
- Operate the continuous drum granulator to improve the continuous plant model
- Study the chosen formulation in a batch granulator to extract rate constants and improve process understanding for the purpose of improved modeling.
After the experimental phase, the Imperial team returned to London to further analyze the experimental batch results and to improve the 3 dimensional process model (papers 2 and 4 in section 8: Publications Resulting from Support) in collaboration with Frantisek Stepanek. The UCSB team returned to Santa Barbara to analyze the continuous data and experiment with several model predictive control algorithms. The team reunited in November in Salt Lake City at the Annual AIChE meeting to present 2 papers and discuss overall progress.
The pilot plant is now ready to be used and fully controlled by MATLAB: it is a good test bed for controllers. However, Jim Litster moved to Purdue this year, and the future of the pilot plant is unclear. Frank Doyle and Constantijn Sanders started experimental work in collaboration with Hong Sing Tan (Newcastle) and Paul Mort (Cincinnati) both of Procter & Gamble. The aim for this collaboration is to demonstrate an MPC setup on an industrial process.
This report is divided in three sections:
- Batch granulation experiments and modeling
- Continuous granulation experiments and modeling
- Continuous granulation control