Particle Formation
Introduction
Crystallography concerns both the internal and external form of a crystal [1]. Crystalline solids are an essential part of our modern technological environment, being important components of pharmaceuticals, foods, cosmetics, metals, ceramics and plastics. The process of crystallisation is used both for purification and as a separation process for the production of particular materials.
The customary way of forming crystals through suspension processes always relies on the usage of solvents in which solution phase is used as a media for homogenisation of the starting composition as well as enabling the molecular assembly processes. These solvents have been found to influence the crystallisation processes to the point of altering both the nucleation rate and the crystal morphologies and state of aggregation of the end product. Despite this, our knowledge and the understanding of the nature of the molecular assembly processes in supersaturated solutions, as well as the interaction of solvents with the crystal faces is severely lacking.
In the fine chemicals and pharmaceutical industries, where products are of high value, organic solvents are routinely used [2]. The ability of solvents to manipulate the structure and morphology of the crystals formed becomes invaluable. This becomes even more important when the drug or the dyestuffs are polymorphic in which case changing the solvent can result in a different polymorph crystallising more than one crystal structure. Modifying the polymorph can alter its physical behaviour. For example, in the case of a drug the rate of uptake in the body can increase making one polymorph more desirable over the other. Thus understanding the interactions between a solvent and solute as well as the fundamental theories lying behind the whole solution crystallisation can increase the performance of the final product as well as extending our ability to select solvents for crystallisation control.
Executive Summary
This report is an integral part of an effort to develop a computational platform to virtually synthesize and test particle compacts based only on the bulk and surface properties of the particles prior to the consolidation process. This virtual manufacturing and testing facility (VMTF) includes die filling, compaction –particle rearrangement and particle deformation (elastic and inelastic)–, compact ejection and subsequent mechanical testing. The current simulation platform is based on a multiscale approach, which bridges systematically the micro and meso-scale. The VMTF will provide the ability to reproduce the behavior of current products but more importantly, it will enable the simulation of systems never yet manufactured, virtually screening the best manufacturing conditions and particle/granule properties for a desired compact behavior or application. During this year we will continue the development of the subsequent modules of die-ejection and mechanical testing.
The specific content of this report includes a numerical study of the mechanical behavior of systems composed by particles with different sizes and materials subjected to consolidation. The simulation methodology is based on a mixed discrete/continuum approach which allows to systematically bridge the microscale response (particle and inter-particle scale) with the mesoscale and macroscopic behavior (container/sample scale). The methodology is particularly suitable for describing the post-rearrangement regime where consolidation proceeds mostly by elastic and inelastic deformation. This formulation is able to provide quantitative estimates of the evolution of macroscopic variables, such as pressure and density, while following microlevel processes, such as local coordination number and loading paths. This methodology is applied to polydispersed systems composed by particles with different nonlinear properties. The predictions are in general agreement with the experimental data during both loading and unloading cycle.
This report summarises progress in IFPRI project 37 in 2001. This is the first year of the continuation project. We have established new areas of investigation with new objectives. Thus, we report here a summary of work in progress at a fairly early stage.
Iveson and Page at The University of Newcastle
have continued to investigate the mechanics of partially saturated powders. For a range of powders, both spherical and non spherical, dimensionless strength is independent of strain rate for Capilliary No (Ca) less than 10-4 and strongly dependent on Ca above this value. Particle shape has a strong effect on yield stress due to its effect on particle packing, friction and particle interlocking. The failure mode also changes with strain rate. At low strain rate, brittle fracture is observed, while at high strain rate pellets deform plastically.
Forrest and Bridgewater at Cambridge University
have established a methodology for characterizing powder flow during granulation using Positron Emission Particle Tracking (PEPT). The technique is being used to study powder flow in a plough share mixer granulator throughout a batch granulation. Powder flow characteristics change significantly as liquid is added to the granulation. Changes in the granule velocity and local bed density are linked to regions of granule motion that are characterised by inter-granule contact time and force. Further experiments are required to determine values for the relaxation ratio and develop the relationship between granule motion and granule properties. Extension of this analysis to a greater range of experimental conditions will develop the relationship between granule motion and granule properties for a ploughshare mixer.
Wet Granule Breakage Research
A brief review of the status of wet granule breakage research is presented. Wet granule breakage is a relatively poorly studied phenomenon. Experimental evidence shows that it may play an important role in controlling granule size distribution in mixer granulators and can contribute significantly to binder distribution under some conditions. However, little attempt has been made to link breakage rates quantitatively to the mechanical properties of the granules (or even to characterise them). The theory of granule breakage and the mechanical characterisation of granules under dynamic conditions need further development in order to produce quantitative predictions of conditions for granule breakage. The work of Tardos and coworkers based on a Stokes deformation number analysis combined with the mechanical characterisation approach of Iveson and Page provide a good starting point for further development.
According to the project work objectives there were the following four aims to be achieved in the second year of the project extension:
- Carrying out validation of drying tests in the counter-current spray drying tower
- Carrying out experimental small-scale drying kinetics tests on selected products
- Comprehensive validation of the CFD model for scaling-up spray drying process in co- and counter-current system
- Carrying out experimental investigations to identify the effect of initial process parameters (feed properties, feed rate, air flow rate, drying temperature, atomization parameters) on the final product properties (porosity, bulk density, solubility, etc.)
This report summarises progress in IFPRI project 37 in 2001/2. The breakage of wet granules in a granulator environment is being studied by Rachel Smith (UQ PhD student). Preliminary results from the dynamic compression of single wet pellets using an Instron Dynamite load frame are reported. The methodology developed by Iveson and Page is used with sone improvements. Fast frame video is used to capture in detail the deformation of the pellets.
The deformation behaviour of the pellets varied widely from very plastic behaviour to failure by brittle crack propagation. Brittle or semi-brittle behaviour was more likely at high strain rate and with high viscosity binders. Pellets made from non-spherical, broad size distribution lactose powder were also more likely to fail in a brittle mode than closely sized glass ballotini pellets. Preliminary results suggest the failure mode can be related to a critical capillary number. The fast frame video analysis of the compression is a very useful tool for understanding the failure behaviour of these partially saturated materials. A hypothesis for wet granule breakage in mixer granulators is suggested and a plan for testing the hypothesis using a specially designed breakage only granulator is presented.
A summary of the PhD studies of Hans Wildeboer on regime separated granulation is given. This work proposes that to optimise granulator design, the key rate processes for granulation should be separated. A conceptual design for a two stage granulator – nucleation only, followed by consolidation and layered growth - is presented. Mathematical models for both stages are developed. The models are compared to results from a partly regime separated continuous drum granulator. The models are very promising in predicting and understanding the granulation behaviour.
A new granulator design is developed which completely separates the nucleation regime from consolidation and growth. A novel nucleation device is tested which gives near mono-sized nuclei at a required size. Further details of Wildeboer’s work are given in his PhD thesis, which will be sent to IFPRI members in early 2003.
The process of disintegration of liquid/solid suspension jets and sheets by atomization is analysed in a fundamental manner and visualized by suitable measurement methods, which allow qualitative and quantitative evaluation of the process. Supporting numerical analysis and theoretical derivations will contribute to basic understanding and control of the suspension atomization process. Model suspensions will be atomized by means of conventional and specifically designed atomizers. The fourth year activities that are reported here include:
- Experimental investigations of suspension atomization in twin-fluid atomizer
- Experimental investigations of suspension atomization in rotary-atomizer
Model suspensions based on water with industrial relevant suspended particles (China Clay) have been atomized by means of twin-fluid atomizer. Model suspensions based on water and water/CMC-(carboxymetylcellulose) mixture with suspended glass particles have been atomized by means of a rotary atomizer.
The rheology of concentrated suspensions containing rigid fillers is important in many technological areas since it mirrors the dynamic behavior of the structuring units, such as disperse particle/particle aggregates as well as macromolecular components (binders) in the continuous fluid phase. For systems with high solid content, air is easily entrapped during different process steps, creating a compressible wet powder. The aim of the work is to investigate the phase transition between a 3-phase wet powder to a 2-phase system suspension (3P2S) occurring in the extrusion processing and to describe its mechanism. Extrusion processing of highly concentrated powder-binder systems always applies uni- or multiaxial shear and/or elongation flow fields, along the screw channel. The main Micro Structuring Mechanism (MSM) acting on the structuring units in such flow process are de-agglomeration, deformation, orientation and agglomeration. The increase of the pressure along the extruder channel and at the die zone, in combination with the high shear stresses present, compress and induce the plastification of the powder system. The 3P2S transition takes place in a well define layer of the final product creating concentric adjacent layer of wet powder and concentrated suspension. Modifying the system components, process steps and operating condition can achieve a different microstructure and distribution of the wet powder/- suspension zones.
The rheology of the model system has been investigated and the solid filler extensively characterized with respect to the agglomerate strength. The 3P2S transition has been investigated in the High Pressure Powder Shear reactor and in extrusion processing. The influence of the mixing quality can show a strong influence on the transition; thus different mixing process has been proposed and NIR spectroscopy has been used to evaluate the quality. Finally the product microstructure has been qualitatively analyzed with scanning electron microscopy (SEM).
Executive Summary
Uniform anatase-type TiO2 nanoparticles of different shapes have been formed by phase transformation of Ti(OH)4 gel matrix in the presence of shape controllers. For example, triethanolamine (TEOA) was found to change the morphology of TiO2 particles from cuboidal to ellipsoidal at pH above 11. The shape control can be explained in terms of the specific adsorption of TEOA to the crystal planes parallel to the c-axis of the tetragonal system in the alkaline range, as supported by the observation of preferential adsorption of TEOA to the crystal planes parallel to the c-axis at pH 11.5 and by the pH dependence of the adsorption to ellipsoidal particles. Diethylenetriamine (DETA) also modified the particle shape to ellipsoidal above pH 9.5 and the aspect ratio was much higher than with TEOA. The mechanism of the shape control could be explained in the same way as with TEOA, since analogous specific adsorption was observed with DETA as well. Similar shape control to yield ellipsoidal particles of a high aspect ratio was also achieved with other primary amines, such as ethylenediamine (ED), trimethylenediamine (TMD), and triethylenetetramine (TETA). However, secondary amines, such as diethylamine, and tertiary amines, such as trimethylamine and triethylamine, acted as a complexing agent of Ti(IV) ion to promote the growth of ellipsoidal particles of a low aspect ratio, rather than a shape controller to produce ellipsoids of a high aspect ratio. Sodium oleate and sodium stearate were found to modify the particle shape from round-cornered cubes to sharp-edged cubes. The mechanism was explained in terms of the reduction of the specific surface energies of the {001} and {100} planes of the tetragonal crystal system by the preferential adsorption of oleate or stearate ion to these planes, based on the adsorption experiment using ellipsoidal and cubic particles.
Introduction
There is enormous potential for utilisation of the solvent to control both the rate processes and product physical form characteristics in the isolation of active materials by crystallisation. This is because, while solvent crystallisation is widely used and solvent choice widely recognised to influence nucleation rates, crystal morphology and aggregation, little is known about the nature of molecular assembly processes in supersaturated solutions nor about the way in which solvents interact with and determine the structure of crystal faces.
This project aims to explore work on solvent effects in nucleation and growth processes, with the initial work exploring the nature between solution chemistry and crystallisation in a polymorphic system, tetrolic acid. This system has been chosen since, it is a simple monocarboxylic acid, CH3C=COOH, for which two crystal structures are known [1] and the difference between dimers and chains of carboxylic acids can be readily detected by a combination of Raman and infrared spectroscopy [2]. In the first year this detection strategy to differentiate between the two crystal packings of carboxylic acids was verified by a range of carboxylic acid and extended to saturated solutions, both yielding promising results. In second year, more emphasis was placed on tetrolic acid with attempts to crystallise and characterise both polymorphic forms, as well as solution spectroscopy utilising the optical probe, transmission cell and HC-32 cell accessories. In addition work has started on the use of atomic force microscopy to image the growing surfaces of molecular crystals with adipic acid chosen as the the first candidate for study.