Process Analytical Technology Approach on Fluid Bed Granulation and Drying : Identifying Critical Relationships and Constructing the Design Space

Fluid bed granulation is a key pharmaceutical process which improves many of the powder properties for tablet compression. Dry mixing, wetting and drying phases are included in the fluid bed granulation process. Granules of high quality can be obtained by understanding and controlling the critical process parameters by timely measurements. Physical process measurements and particle size data of a fluid bed granulator that are analysed in an integrated manner are included in process analytical technologies (PAT). Recent regulatory guidelines strongly encourage the pharmaceutical industry to apply scientific and risk management approaches to the development of a product and its manufacturing process. The aim of this study was to utilise PAT tools to increase the process understanding of fluid bed granulation and drying. Inlet air humidity levels and granulation liquid feed affect powder moisture during fluid bed granulation. Moisture influences on many process, granule and tablet qualities. The approach in this thesis was to identify sources of variation that are mainly related to moisture. The aim was to determine correlations and relationships, and utilise the PAT and design space concepts for the fluid bed granulation and drying. Monitoring the material behaviour in a fluidised bed has traditionally relied on the observational ability and experience of an operator. There has been a lack of good criteria for characterising material behaviour during spraying and drying phases, even though the entire performance of a process and end product quality are dependent on it. The granules were produced in an instrumented bench-scale Glatt WSG5 fluid bed granulator. The effect of inlet air humidity and granulation liquid feed on the temperature measurements at different locations of a fluid bed granulator system were determined. This revealed dynamic changes in the measurements and enabled finding the most optimal sites for process control. The moisture originating from the granulation liquid and inlet air affected the temperature of the mass and pressure difference over granules. Moreover, the effects of inlet air humidity and granulation liquid feed rate on granule size were evaluated and compensatory techniques used to optimize particle size. Various end-point indication techniques of drying were compared. The ∆T method, which is based on thermodynamic principles, eliminated the effects of humidity variations and resulted in the most precise estimation of the drying end-point. The influence of fluidisation behaviour on drying end-point detection was determined. The feasibility of the ∆T method and thus the similarities of end-point moisture contents were found to be dependent on the variation in fluidisation between manufacturing batches. A novel parameter that describes behaviour of material in a fluid bed was developed. Flow rate of the process air and turbine fan speed were used to calculate this parameter and it was compared to the fluidisation behaviour and the particle size results. The design space process trajectories for smooth fluidisation based on the fluidisation parameters were determined. With this design space it is possible to avoid excessive fluidisation and improper fluidisation and bed collapse. Furthermore, various process phenomena and failure modes were observed with the in-line particle size analyser. Both rapid increase and a decrease in granule size could be monitored in a timely manner. The fluidisation parameter and the pressure difference over filters were also discovered to express particle size when the granules had been formed. The various physical parameters evaluated in this thesis give valuable information of fluid bed process performance and increase the process understanding.

An exploratory study on the commercialisation of heat pump-fluidised bed drying technology

Fluidised bed-heat pump drying technology offers distinctive advantages over the existing drying technology employed in the Australian food industry. However, as is the case with many other examples of innovations that have had clear relative advantages, the rates of adoption and diffusion of this technology have been very slow. "Why does this happen?" is the theme of this research study that has been undertaken with an objective to analyse a range of issues related to the market acceptance of technological innovations. The research methodology included the development of an integrated conceptual model based on an extensive review of literature in the areas of innovation diffusion, technology transfer and industrial marketing. Three major determinants associated with the market acceptance of innovations were identified as the characteristics of the innovation, adopter information processing capability and the influence of the innovation supplier on the adoption process. This was followed by a study involving more than 30 small and medium enterprises identified as potential adopters of fluidised bed-heat pump drying technology in the Australian food industry. The findings revealed that judgment was the key evaluation strategy employed by potential adopters in the particular industry sector. Further, it was evidenced that the innovations were evaluated against a predetermined criteria covering a range of aspects with emphasis on a selected set of attributes of the innovation. Implication of these findings on the commercialisation of fluidised bed-heat pump drying technology was established, and a series of recommendations was made to the innovation supplier (DPI/FT) enabling it to develop an effective commercialisation strategy.

Direct shear testing on unsaturated silty soils to investigate the effects of drying and wetting on shear strength parameters at low suction

A modified conventional direct shear device was used to measure unsaturated shear strength of two silty soils at low suction values (0 ~ 50 kPa) that were achieved by following drying and wetting paths of soil water characteristic curves (SWCCs). The results revealed that the internal friction angle of the soils was not significantly affected by either the suction or the drying wetting SWCCs. The apparent cohesion of soil increased with a decreasing rate as suction increased. Shear stress-shear displacement curves obtained from soil specimens subjected to the same net normal stress and different suction values showed a higher initial stiffness and a greater peak stress as suction increased. A soil in wetting exhibited slightly higher peak shear stress and more contractive volume change behavior than that of soil in drying at the same net normal stress and suction.

Aseptic Processing of Foods Containing Particulates

Aseptic processing involves sterilising the product and package separately, and filling under sterile conditions. Advantages include better product quality compared with canned products, lower transport and storage costs compared with frozen products, and virtually no restriction on package size. Problems include ensuring adequate heat penetration into the particles to ensure sterility, preventing separation of particles from the carrier liquid, and retention of particle structure and shape. Particulate foods can be sterilised in scraped - surface heat exchangers. Other methods involve heating the particles separately, and combining them during filling. Projects will commence at the International Food Institute of Queensland (IFIQ) on aseptic packaging of a meat and vegetable product, and aseptically packaged mango pieces.

Exploring the potential of VIS-NIR spectroscopy to predict sensory properties of foods

Sensory analysis of food involves the measurement, interpretation and understanding of human responses to the properties of food perceived by the senses such as sight, smell, and taste (Cozzolino et al. 2005). It is important to have a quantitative means for assessing sensory properties in a reasonable way, to enable the food industry to rapidly respond to the changing demands of both consumers and the market. Aroma and flavour are among the most important properties for the consumer and numerous studies have been performed in attempts to find correlations between sensory qualities and objective instrumental measurements. Rapid, non-destructive instrumental methods such as near infrared spectroscopy (NIR) might be advantageous to predict quality of food and agricultural products due to the speed of analysis, minimum sample preparation and low cost. The advantages of such technologies are not only to assess chemical structures but also to build a spectrum, characteristic of the sample, which behaves as a “finger print”.

Foods of pigeons and doves in fragmented landscapes of subtropical eastern Australia

We report dietary items of pigeons and doves from northern New South Wales and southern Queensland, obtained from opportunistic sampling of the gut contents of dead birds and observing foraging birds. Most records were from fragmented rainforest habitats, which now support abundant invasive fleshy-fruited plants. The fruits and seeds of invasive plants, particularly Camphor Laurel Cinnamomum camphora, formed the dominant food of several of the species sampled, although in some cases these birds appear to destroy most of the ingested seeds in the gizzard, thereby not contributing to weed dispersal. We also describe the first records of White-headed Pigeons Columba leucomela eating flowers and Brown Cuckoo-Doves Macropygia amboinensis eating flower buds. Camphor Laurel, via flowers, green and ripe fruits, and seeds, provided food for White-headed Pigeons in the Goolmangar district of New South Wales throughout the entire year. Seventy percent of the plant species whose fruits and seeds were recovered from the gut had not previously been recorded as food items for those bird species, illustrating how little is known about the diets of pigeons and doves in fragmented Australian landscapes.

Accelerated drying of plantation grown Eucalyptus cloeziana and Eucalyptus pellita sawn timber

The objective of this study was to gain an understanding for drying sawn timber produced from fast-grown, well-managed Queensland hardwood plantations using accelerated drying methods. Due to limited resources, this was a preliminary study and further work will be required to optimize schedules for industrial implementation. Three conventional kiln trials, including two for 38-mm-thick, 19-year-old plantation Gympie messmate (Eucalyptus cloeziana F. Muell.) and one for 25mm thick, 15-year-old plantation red mahogany (Eucalyptus pellita F. Muell.), and two vacuum kiln drying trials, one each for 38- and 25mm thick Gympie messmate, were conducted. Measurements of final cross-sectional moisture content, moisture content gradient, residual drying stress, and internal and surface checking were used to quantify dried quality. Drying schedules were chosen based on either existing published schedules or, in the case of the vacuum drying trials, existing schedules for species with similar wood density and dying degrade properties, or manipulated schedules based on the results of trials conducted during this study. The findings indicate that both species can be dried using conventional drying techniques with acceptable grade quality in approximately 75 percent of the drying time that industry is currently achieving when drying native forest timber of the same species. The vacuum drying time was 60 percent less than conventional drying for 38-mm-thick, 19-year-old Gympie messmate, although drying quality needs improving. The findings have shown that through careful schedule manipulation and adjustment, the grade quality can be optimized to suit the desired expectation. Additional research is required to further optimize the schedules to ensure acceptable grade qualities can be reliably achieved across all drying criteria and exploit opportunities to reduce drying times further.

Characterisation of wood properties and transverse anatomy for vacuum drying modelling of commercially important Australian hardwood species.

Characterisation and investigation of a number of key wood properties, critical for further modelling work, has been achieved. The key results were: • Morphological characterisation, in terms of fibre cell wall thickness and porosity, was completed. A clear difference in fibre porosity, size, wall thickness and orientation was evident between species. Results were consistent with published data for other species. • Viscoelastic properties of wood were shown to differ greatly between species and in the radial and tangential directions, largely due to anatomical and chemical variations. Consistent with published data, the radial direction shows higher stiffness, internal friction and glass transition temperature than the tangential directions. The loss of stiffness over the measured temperature range was greater in the tangential direction than the radial direction. Due to time dependant molecular relaxation, the storage modulus and glass transition temperature decreased with decreasing test frequency, approaching an asymptotic limit. Thus the viscoelastic properties measured at lower frequencies are more representative of static material. • Dynamic interactions between relative humidity, moisture content and shrinkage of four Australian hardwood timbers can be accurately monitored on micro-samples using a specialised experimental device developed by AgroParisTech – ENGREF. The device generated shrinkage data that varied between species but were consistent (repeatable) within a species. Collapse shrinkage was clearly evident with this method for Eucalyptus obliqua, but not with other species, consistent with industrial seasoning experience. To characterise the wood-water relations of this species, free of collapse, thinner sample sections (in the R-T plane) should be used.

Defining the unique flavours of Australian native foods

Australian native plant foods provide new and exciting eating experiences for consumers and have the potential to re-position ‘Australian cuisine’ as a contemporary food choice for consumers worldwide. The development of a common set of flavour and aroma descriptors and characteristics was identified as a key priority for the Australian native food industry. This research assists in the development and supply of product information to support market access and market growth for this emerging industry. This work was targeted so that a concise, consistent and accurate marketing message of the flavours of these ingredients could be delivered to customers. This report details the results of the development of the first ‘Australian native flavour wheel’ and sensory descriptions for sixteen of the key commercial native food species including fruits, berries, herbs, spices and seeds.

Hardwood Drying Length Evaluation

Evaluating the length of time required to dry hardwood timber using vacuum drying compared to conventional drying facilities and technology.

PN08.2047 Vacuum Drying

Research the viability of vacuum drying Australian commercially important hardwood species.

Computational Modelling of the Vacuum Drying of Australian Hardwoods

Computational Modelling of the Vacuum Drying of Australian Hardwoods.

Australian hardwood drying best practice manual. Part 2

This manual is a guide to establishing a set of operations to achieve high grade results in product quality and recovery, flexibility, innovation, cost, and competitiveness. The manual outlines: - economic and feasible technologies for increasing recovery and reducing avoidable loss during processing, from the log to the finished board, and - mechanisms that allow production value to be optimised in different sized mills. Part 2 includes sections 8 to 17: Air drying, pre-drying, reconditioning, controlled final drying, dry milling, storage, information assessment, drying quality assessment, moisture content monitoring, glossary. Part 1 Link: http://era.deedi.qld.gov.au/3138 Covers sections 1 to 7: Drying overview and strategy, coupe, log yard, green mill, green pack, bioprotection, rack timber.

Australian hardwood drying best practice manual. Part 1

This manual is a guide to establishing a set of operations to achieve high grade results in product quality and recovery, flexibility, innovation, cost, and competitiveness. The manual outlines: - economic and feasible technologies for increasing recovery and reducing avoidable loss during processing, from the log to the finished board, and - mechanisms that allow production value to be optimised in different sized mills. Part 1 covers sections 1 to 7: Drying overview and strategy, coupe, log yard, green mill, green pack, bioprotection, rack timber. Part 2 Link: http://era.deedi.qld.gov.au/3137 Includes sections 8 to 17: Air drying, pre-drying, reconditioning, controlled final drying, dry milling, storage, information assessment, drying quality assessment, moisture content monitoring, glossary.