Systematic screening of compressed ODT excipients:cellulosic versus non-cellulosic

The successful development of compressed ODTs utilises low compression forces to create a porous structure whereby excipients are added to enhance wicking/swelling action or provide strength to the fragile tablet framework. In this work, a systematic investigation comparing materials from two different categories was employed to understand their functionality in binary mixture tablets of the most commonly used diluent mannitol. Cellulose based excipients such as HPC (SSL-SFP), L-HPC (NBD-022) and MCC (Avicel PH-102) were compared with non-cellulosic materials such as PEO (POLYOX WSR N-10) and Crospovidone (XL-10). Pure excipient properties were studied using Heckel Plot, compressibility profile, SEM and XRPD, whereas the prepared binary mixture compacts were studied for hardness, disintegration time and friability. Results from our investigation provide insight into differences encountered in product performance of ODT upon inclusion of additional materials. For example, non-cellulosic excipients Polyox and Crospovidone showed higher plasticity (Py values 588 and 450MPa) in pure form but not in binary mixtures of mannitol. Cellulosic excipients, nonetheless, offer faster disintegration (<30 sec) specifically L-HPC and MCC tablets. Disintegration time for tablets with fully substituted-HPC was prolonged (200-500 sec) upon increasing concentration between 1-10% due to gelation/matrix formation. It can be concluded that despite the reasonably good plasticity of both cellulosic and non-cellulosic excipients in pure form, the mechanical strength in binary mixtures is negatively impacted by the fragmentation/fracture effect of mannitol. © 2014 Bentham Science Publishers.

Systematic screening of compressed ODT excipients : cellulosic versus non-cellulosic

The successful development of c ompressed ODTs utilises low compression force s to create a porous structure whereby excipients are added to enhance wicking/swelling action or p rovide strength to the fragile tablet framework. In this work, a systematic investigation comparing materials from two different categories was employed to understand their functionality in binary mixture tablets of the most commonly used diluent mannitol. Cellulose based excipients such as HPC (SSL-SFP), L-HPC (NBD -022) and MCC (Avicel PH -102 ) were compared with non -cellulosic materials such as PEO (POLYOX WSR N -10) and Crospovidone (XL -10). P ure excipient properties were studied using Heckel Plot, compre ssibility profile, SEM and XR PD, w hereas the prepared binary mixture compacts were studied for hardness, disintegration time and friability. Results from our investigation provide insight into differences encountered in product performance of ODT upon inclusion of additional materials. For example, non -cellulosic excipients Polyox and Crospovidone showed higher plasticity (Py values 588 and 450 MPa) in pure form but not in binary mixtures of mannitol . Cellulosic excipients, nonetheless, offer faster disintegration (

Evidence-based nanoscopic and molecular framework for excipient functionality in compressed orally disintegrating tablets

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2-10 μm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. © 2014 Al-khattawi et al.

Challenges and emerging solutions in the development of compressed orally disintegrating tablets

Areas covered: The review discusses the main challenges of ODT manufacturing process and the emerging solutions featured at early drug development stages. The research specifically describes the methods reported for taste masking/assessment and solubilisation of unpalatable and poorly soluble drugs, respectively. Furthermore, this review highlights the techniques used for developing modified-release ODTs, an emerging area in the field. In addition, it also discusses the poor flowability and segregation problems of directly compressed powders. Moreover, the review describes the tests reported in the literature for ODT disintegration time assessment since a universal technique is still non-existent. Expert opinion: The approaches used to overcome the manufacturing challenges often have a bearing on the price of the end product. However, despite the technical and regulatory challenges, ODTs can offer many advantages over the conventional dosage forms if accompanied by suitable adjuvant technologies and in vitro analytical tools. © 2014 Informa UK, Ltd. Introduction: Orally disintegrating tablets (ODTs) provide several advantages over conventional tablets such as suitability for patients with swallowing difficulties and faster onset of action. The manufacture of ODTs by compression/tableting offers a practical and cost-effective strategy over the freeze drying (lyophilisation) method. Nonetheless, the FDA recommends a disintegration time of 30 s and a maximum weight of 500 mg for a tablet to be labelled as an ODT. These requirements, alongside other desirable product properties, have created a number of challenges for the formulator to overcome while developing compressed ODTs.

Excipient characterization and particle engineering to develop directly compressed orally disintegrating tablets

ODTs have emerged as a novel oral dosage form with a potential to deliver a wide range of drug candidates to paediatric and geriatric patients. Compression of excipients offers a costeffective and translatable methodology for the manufacture of ODTs. Though, technical challenges prevail such as difficulty to achieve suitable tablet mechanical strength while ensuring rapid disintegration in the mouth, poor compressibility of preferred ODT diluent Dmannitol, and limited use for modified drug-release. The work investigates excipients’ functionality in ODTs and proposes new methodologies for enhancing material characteristics via process and particle engineering. It also aims to expand ODT applications for modified drug-release. Preformulation and formulation studies employed a plethora of techniques/tests including AFM, SEM, DSC, XRD, TGA, HSM, FTIR, hardness, disintegration time, friability, stress/strain and Heckel analysis. Tableting of D-mannitol and cellulosic excipients utilised various compression forces, material concentrations and grades. Engineered D-mannitol particles were made by spray drying mannitol with pore former NH4HCO3. Coated microparticles of model API omeprazole were prepared using water-based film forming polymers. The results of nanoscopic investigations elucidated the compression profiles of ODT excipients. Strong densification of MCC (Py is 625 MPa) occurs due to conglomeration of physicomechanical factors whereas D-mannitol fragments under pressure leading to poor compacts. Addition of cellulosic excipients (L-HPC and HPMC) and granular mannitol to powder mannitol was required to mechanically strengthen the dosage form (hardness >60 N, friability <1%) and to maintain rapid disintegration (<30 sec). Similarly, functionality was integrated into D-mannitol by fabrication of porous, yet, resilient particles which resulted in upto 150% increase in the hardness of compacts. The formulated particles provided resistance to fracture under pressure due to inherent elasticity while promoted tablet disintegration (50-77% reduction in disintegration time) due to porous nature. Additionally, coated microparticles provided an ODT-appropriate modified-release coating strategy by preventing drug (omeprazole) release.

A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets

The acceleration of solid dosage form product development can be facilitated by the inclusion of excipients that exhibit poly-/multi-functionality with reduction of the time invested in multiple excipient optimisations. Because active pharmaceutical ingredients (APIs) and tablet excipients present diverse densification behaviours upon compaction, the involvement of these different powders during compaction makes the compaction process very complicated. The aim of this study was to assess the macrometric characteristics and distribution of surface charges of two powders: indomethacin (IND) and arginine (ARG); and evaluate their impact on the densification properties of the two powders. Response surface modelling (RSM) was employed to predict the effect of two independent variables; Compression pressure (F) and ARG percentage (R) in binary mixtures on the properties of resultant tablets. The study looked at three responses namely; porosity (P), tensile strength (S) and disintegration time (T). Micrometric studies showed that IND had a higher charge density (net charge to mass ratio) when compared to ARG; nonetheless, ARG demonstrated good compaction properties with high plasticity (Y=28.01MPa). Therefore, ARG as filler to IND tablets was associated with better mechanical properties of the tablets (tablet tensile strength (σ) increased from 0.2±0.05N/mm2 to 2.85±0.36N/mm2 upon adding ARG at molar ratio of 8:1 to IND). Moreover, tablets' disintegration time was shortened to reach few seconds in some of the formulations. RSM revealed tablet porosity to be affected by both compression pressure and ARG ratio for IND/ARG physical mixtures (PMs). Conversely, the tensile strength (σ) and disintegration time (T) for the PMs were influenced by the compression pressure, ARG ratio and their interactive term (FR); and a strong correlation was observed between the experimental results and the predicted data for tablet porosity. This work provides clear evidence of the multi-functionality of ARG as filler, binder and disintegrant for directly compressed tablets.

Classification of Texts' Authorship Using a Regression Model on Compressed Data

2010 Mathematics Subject Classification: 68T50,62H30,62J05.

Image usefulness of compressed surveillance footage with different scene contents

The police use both subjective (i.e. police staff) and automated (e.g. face recognition systems) methods for the completion of visual tasks (e.g person identification). Image quality for police tasks has been defined as the image usefulness, or image suitability of the visual material to satisfy a visual task. It is not necessarily affected by any artefact that may affect the visual image quality (i.e. decrease fidelity), as long as these artefacts do not affect the relevant useful information for the task. The capture of useful information will be affected by the unconstrained conditions commonly encountered by CCTV systems such as variations in illumination and high compression levels. The main aim of this thesis is to investigate aspects of image quality and video compression that may affect the completion of police visual tasks/applications with respect to CCTV imagery. This is accomplished by investigating 3 specific police areas/tasks utilising: 1) the human visual system (HVS) for a face recognition task, 2) automated face recognition systems, and 3) automated human detection systems. These systems (HVS and automated) were assessed with defined scene content properties, and video compression, i.e. H.264/MPEG-4 AVC. The performance of imaging systems/processes (e.g. subjective investigations, performance of compression algorithms) are affected by scene content properties. No other investigation has been identified that takes into consideration scene content properties to the same extend. Results have shown that the HVS is more sensitive to compression effects in comparison to the automated systems. In automated face recognition systems, `mixed lightness' scenes were the most affected and `low lightness' scenes were the least affected by compression. In contrast the HVS for the face recognition task, `low lightness' scenes were the most affected and `medium lightness' scenes the least affected. For the automated human detection systems, `close distance' and `run approach' are some of the most commonly affected scenes. Findings have the potential to broaden the methods used for testing imaging systems for security applications.

Distributed and compressed MIKEY mode to secure end-to-end communications in the Internet of things.

Multimedia Internet KEYing protocol (MIKEY) aims at establishing secure credentials between two communicating entities. However, existing MIKEY modes fail to meet the requirements of low-power and low-processing devices. To address this issue, we combine two previously proposed approaches to introduce a new distributed and compressed MIKEY mode for the Internet of Things. Indeed, relying on a cooperative approach, a set of third parties is used to discharge the constrained nodes from heavy computational operations. Doing so, the preshared mode is used in the constrained part of network, while the public key mode is used in the unconstrained part of the network. Furthermore, to mitigate the communication cost we introduce a new header compression scheme that reduces the size of MIKEY’s header from 12 Bytes to 3 Bytes in the best compression case. Preliminary results show that our proposed mode is energy preserving whereas its security properties are preserved untouched.

Dynamic model development of adiabatic compressed air energy storage

The share of variable renewable energy in electricity generation has seen exponential growth during the recent decades, and due to the heightened pursuit of environmental targets, the trend is to continue with increased pace. The two most important resources, wind and insolation both bear the burden of intermittency, creating a need for regulation and posing a threat to grid stability. One possibility to deal with the imbalance between demand and generation is to store electricity temporarily, which was addressed in this thesis by implementing a dynamic model of adiabatic compressed air energy storage (CAES) with Apros dynamic simulation software. Based on literature review, the existing models due to their simplifications were found insufficient for studying transient situations, and despite of its importance, the investigation of part load operation has not yet been possible with satisfactory precision. As a key result of the thesis, the cycle efficiency at design point was simulated to be 58.7%, which correlated well with literature information, and was validated through analytical calculations. The performance at part load was validated against models shown in literature, showing good correlation. By introducing wind resource and electricity demand data to the model, grid operation of CAES was studied. In order to enable the dynamic operation, start-up and shutdown sequences were approximated in dynamic environment, as far as is known, the first time, and a user component for compressor variable guide vanes (VGV) was implemented. Even in the current state, the modularly designed model offers a framework for numerous studies. The validity of the model is limited by the accuracy of VGV correlations at part load, and in addition the implementation of heat losses to the thermal energy storage is necessary to enable longer simulations. More extended use of forecasts is one of the important targets of development, if the system operation is to be optimised in future.

Revisiting compressed air energy storage.

The use of renewable energies as a response to the EU targets defined for 2030 Climate Change and Energy has been increasing. Also non-dispatchable and intermittent renewable energies like wind and solar cannot generally match supply and demand, which can also cause some problems in the grid. So, the increased interest in energy storage has evolved and there is nowadays an urgent need for larger energy storage capacity. Compressed Air Energy Storage (CAES) is a proven technology for storing large quantities of electrical energy in the form of high-pressure air for later use when electricity is needed. It exists since the 1970’s and is one of the few energy storage technologies suitable for long duration (tens of hours) and utility scale (hundreds to thousands of MW) applications. It is also one of the most cost-effective solutions for large to small scale storage applications. Compressed Air Energy Storage can be integrated and bring advantages to different levels of the electric system, from the Generation level, to the Transmission and Distribution levels, so in this paper a revisit of CAES is done in order to better understand what and how it can be used for our modern needs of energy storage.

Improvements in sustainable energy and water practice in the food processing industry : an in depth analysis of the manufacture of Ghee at the Butter Producers' Cooperative Federation Limited, Brisbane

This thesis is a documented energy audit and long term study of energy and water reduction in a ghee factory. Global production of ghee exceeds 4 million tonnes annually. The factory in this study refines dairy products by non-traditional centrifugal separation and produces 99.9% pure, canned, crystallised Anhydrous Milk Fat (Ghee). Ghee is traditionally made by batch processing methods. The traditional method is less efficient, than centrifugal separation. An in depth systematic investigation was conducted of each item of major equipment including; ammonia refrigeration, a steam boiler, canning equipment, pumps, heat exchangers and compressed air were all fine-tuned. Continuous monitoring of electrical usage showed that not every initiative worked, others had pay back periods of less than a year. In 1994-95 energy consumption was 6,582GJ and in 2003-04 it was 5,552GJ down 16% for a similar output. A significant reduction in water usage was achieved by reducing the airflow in the refrigeration evaporative condensers to match the refrigeration load. Water usage has fallen 68% from18ML in 1994-95 to 5.78ML in 2003-04. The methods reported in this thesis could be applied to other industries, which have similar equipment, and other ghee manufacturers.

What about me? Avoiding fatigue and gaining personal time in the work to leisure transition in work-life balance initiatives

Fatigue and overwork are problems experienced by numerous employees in many industry sectors. Focusing on improving work-life balance can frame the ‘problem’ of long work hours to resolve working time duration issues. Flexible work options through re-organising working time arrangements is key to developing an organisational response for delivering work-life balance and usually involves changing the internal structure of work time. This study examines the effect of compressed long weekly working hours and the consequent ‘long break’ on work-life balance. Using Spillover theory and Border theory, this research considers organisational and personal determinants of overwork and fatigue. It concludes compressed long work hours with a long break provide better work-life balance. Further, a long break allows gaining ‘personal time’ and overcoming fatigue.

Simulation and development of a mock circulation loop with variable compliance

Heart disease is attributed as the highest cause of death in the world. Although this could be alleviated by heart transplantation, there is a chronic shortage of donor hearts and so mechanical solutions are being considered. Currently, many Ventricular Assist Devices (VADs) are being developed worldwide in an effort to increase life expectancy and quality of life for end stage heart failure patients. Current pre-clinical testing methods for VADs involve laboratory testing using Mock Circulation Loops (MCLs), and in vivo testing in animal models. The research and development of highly accurate MCLs is vital to the continuous improvement of VAD performance. The first objective of this study was to develop and validate a mathematical model of a MCL. This model could then be used in the design and construction of a variable compliance chamber to improve the performance of an existing MCL as well as form the basis for a new miniaturised MCL. An extensive review of literature was carried out on MCLs and mathematical modelling of their function. A mathematical model of a MCL was then created in the MATLAB/SIMULINK environment. This model included variable features such as resistance, fluid inertia and volumes (resulting from the pipe lengths and diameters); compliance of Windkessel chambers, atria and ventricles; density of both fluid and compressed air applied to the system; gravitational effects on vertical columns of fluid; and accurately modelled actuators controlling the ventricle contraction. This model was then validated using the physical properties and pressure and flow traces produced from a previously developed MCL. A variable compliance chamber was designed to reproduce parameters determined by the mathematical model. The function of the variability was achieved by controlling the transmural pressure across a diaphragm to alter the compliance of the system. An initial prototype was tested in a previously developed MCL, and a variable level of arterial compliance was successfully produced; however, the complete range of compliance values required for accurate physiological representation was not able to be produced with this initial design. The mathematical model was then used to design a smaller physical mock circulation loop, with the tubing sizes adjusted to produce accurate pressure and flow traces whilst having an appropriate frequency response characteristic. The development of the mathematical model greatly assisted the general design of an in vitro cardiovascular device test rig, while the variable compliance chamber allowed simple and real-time manipulation of MCL compliance to allow accurate transition between a variety of physiological conditions. The newly developed MCL produced an accurate design of a mechanical representation of the human circulatory system for in vitro cardiovascular device testing and education purposes. The continued improvement of VAD test rigs is essential if VAD design is to improve, and hence improve quality of life and life expectancy for heart failure patients.

Spectral coding methods for speech compression and speaker identification

This thesis investigates aspects of encoding the speech spectrum at low bit rates, with extensions to the effect of such coding on automatic speaker identification. Vector quantization (VQ) is a technique for jointly quantizing a block of samples at once, in order to reduce the bit rate of a coding system. The major drawback in using VQ is the complexity of the encoder. Recent research has indicated the potential applicability of the VQ method to speech when product code vector quantization (PCVQ) techniques are utilized. The focus of this research is the efficient representation, calculation and utilization of the speech model as stored in the PCVQ codebook. In this thesis, several VQ approaches are evaluated, and the efficacy of two training algorithms is compared experimentally. It is then shown that these productcode vector quantization algorithms may be augmented with lossless compression algorithms, thus yielding an improved overall compression rate. An approach using a statistical model for the vector codebook indices for subsequent lossless compression is introduced. This coupling of lossy compression and lossless compression enables further compression gain. It is demonstrated that this approach is able to reduce the bit rate requirement from the current 24 bits per 20 millisecond frame to below 20, using a standard spectral distortion metric for comparison. Several fast-search VQ methods for use in speech spectrum coding have been evaluated. The usefulness of fast-search algorithms is highly dependent upon the source characteristics and, although previous research has been undertaken for coding of images using VQ codebooks trained with the source samples directly, the product-code structured codebooks for speech spectrum quantization place new constraints on the search methodology. The second major focus of the research is an investigation of the effect of lowrate spectral compression methods on the task of automatic speaker identification. The motivation for this aspect of the research arose from a need to simultaneously preserve the speech quality and intelligibility and to provide for machine-based automatic speaker recognition using the compressed speech. This is important because there are several emerging applications of speaker identification where compressed speech is involved. Examples include mobile communications where the speech has been highly compressed, or where a database of speech material has been assembled and stored in compressed form. Although these two application areas have the same objective - that of maximizing the identification rate - the starting points are quite different. On the one hand, the speech material used for training the identification algorithm may or may not be available in compressed form. On the other hand, the new test material on which identification is to be based may only be available in compressed form. Using the spectral parameters which have been stored in compressed form, two main classes of speaker identification algorithm are examined. Some studies have been conducted in the past on bandwidth-limited speaker identification, but the use of short-term spectral compression deserves separate investigation. Combining the major aspects of the research, some important design guidelines for the construction of an identification model when based on the use of compressed speech are put forward.