119 resultados para Manufacturing Process


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Background aims: The selection of medium and associated reagents for human mesenchymal stromal cell (hMSC) culture forms an integral part of manufacturing process development and must be suitable for multiple process scales and expansion technologies. Methods: In this work, we have expanded BM-hMSCs in fetal bovine serum (FBS)- and human platelet lysate (HPL)-containing media in both a monolayer and a suspension-based microcarrier process. Results: The introduction of HPL into the monolayer process increased the BM-hMSC growth rate at the first experimental passage by 0.049 day and 0.127/day for the two BM-hMSC donors compared with the FBS-based monolayer process. This increase in growth rate in HPL-containing medium was associated with an increase in the inter-donor consistency, with an inter-donor range of 0.406 cumulative population doublings after 18 days compared with 2.013 in FBS-containing medium. Identity and quality characteristics of the BM-hMSCs are also comparable between conditions in terms of colony-forming potential, osteogenic potential and expression of key genes during monolayer and post-harvest from microcarrier expansion. BM-hMSCs cultured on microcarriers in HPL-containing medium demonstrated a reduction in the initial lag phase for both BM-hMSC donors and an increased BM-hMSC yield after 6 days of culture to 1.20 ± 0.17 × 105 and 1.02 ± 0.005 × 105 cells/mL compared with 0.79 ± 0.05 × 105 and 0.36 ± 0.04 × 105 cells/mL in FBS-containing medium. Conclusions: This study has demonstrated that HPL, compared with FBS-containing medium, delivers increased growth and comparability across two BM-hMSC donors between monolayer and microcarrier culture, which will have key implications for process transfer during scale-up.

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Orally disintegrating Tablets (ODTs), also known as fast-disintegrating, fast-melt or fast-dissolving tablets, are a relatively novel dosage technology that involves the rapid disintegration or dissolution of the dosage form into a solution or suspension in the mouth without the need for water. The solution containing the active ingredients is swallowed, and the active ingredients are then absorbed through the gastrointestinal epithelium to reach the target and produce the desired effect. Formulation of ODTs was originally developed to address swallowing difficulties of conventional solid oral dosage forms (tablets and capsules) experienced by wide range of patient population, especially children and elderly. The current work investigates the formulation and development of ODTs prepared by freeze drying. Initial studies focused on formulation parameters that influence the manufacturing process and performance of lyophilised tablets based on excipients used in commercial products (gelatin and saccharides). The second phase of the work was followed up by comprehensive studies to address the essential need to create saccharide free ODTs using naturally accruing amino acids individually or in combinations. Furthermore, a factorial design study was carried out to investigate the feasibility of delivering multiparticulate systems of challenging drugs using a novel formulation that exploited the electrostatic associative interaction between gelatin and carrageenan. Finally, studies aimed to replace gelatin with ethically and morally accepted components to the end users were performed and the selected binder was used in factorial design studies to investigate and optimise ODT formulations that incorporated drugs with varies physicochemical properties. Our results show that formulation of elegant lyophilised ODTs with instant disintegration and adequate mechanical strength requires carful optimisation of gelatin concentration and bloom strength in addition to saccharide type and concentration. Successful formulation of saccharides free lyophilised ODTs requires amino acids that crystallise in the frozen state or display relatively high Tg', interact and integrate completely with the binder and, also, display short wetting time with the disintegrating medium. The use of an optimised mixture of gelatin, carrageenan and alanine was able to create viscous solutions to suspend multiparticulate systems and at the same time provide tablets with short disintegration times and adequate mechanical properties. On the other hand, gum arabic showed an outstanding potential for use as a binder in the formulation of lyophilised ODTs. Compared to gelatin formulations, the use of gum arabic simplified the formulation stages, shortened the freeze drying cycles and produced tablets with superior performance in terms of the disintegration time and mechanical strength. Furthermore, formulation of lyophilised ODTs based on gum arabic showed capability to deliver diverse range of drugs with advantages over commercial products.

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The development of ideas and theories concerning the structure of glazes, as one of the glassy materials, are reviewed in the general introduction. The raw materials and the manufacturing process for glazes are described (Chapter One). A number of new vanadyl(IV) dipyridylamine and tripyrldylamine complexes have been prepared, various spectroscopic techniques are used in the investigation of the vanadyl ion in a weak ligand field, the situation of those found in a glaze environment (Chapter Three). In glaze recipes containing silica, potash feldspar, china clay, MO(M= Ca, Sr, Sa, Ti and Zn) and NiO, the ligand field theory is used in the elucidation of the effect of M (in MO) on the absorption spectra and coordination behaviour of Ni(II) in glazes. The magnetic and visible spectral results are reviewed in terms of Dietzel's idea of field strength of M and also in terms of Shteinberg's theory of glaze structure. X-ray diffraction is used for the identification of various species that formed after the firing process of glazes (Chapter Four). In Chapter Five, [] Mossbauer spectroscopy, supplemented by E.S.R., X-ray and visible spectral measurements are used in the investigation of iron in a glaze composition similar to that used in Chapter Four. The Mossbauer results are used in following the influence of; M in MO (M= Sr, Ca and Ba), oxides of titanium(IV) and vanadium(V ), and firing conditions on the chemistry of iron. Generally the iron(II) and iron(III) in the fired glazes are in octahedral sites although there are a range of similar, though not identical environments. A quite noticable influence of M (in MO) on the resonance line width is seen. In one case evidence is found for iron(IV) in an iron/vanadium glaze. E.S.R. of vanadium containing glazes indicate that vanadium is present as V02+ in a highly distorted tetragonal environment .

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This paper assumes that a primary function of management accounting is the representation of "accounting facts" for purposes such as organizational control. Accountants are able to offer conventional techniques of control, such as standard costing, as a consequence of their ability to deploy accounting representations within managerial and economic models of organizational processes. Accounting competes, at times, with other 'professional' groups, such as production planning or quality management people, in this role of representing the organization to management. The paper develops its arguments around a case illustration of cost accounting set in a low technology manufacturing environment. The research relates to a case organization in which accountants are attempting to establish the reliability of accounting inscriptions of a simple manufacturing process. The case research focuses on the documents, the inscriptions that vie for managements' attention. It is these sometimes messy and inaccurate representations which enable control of complex and heterogeneous activities at a distance. At the end of our site visits we observe quality management systems in the ascendancy over the accountants' standard costing systems. © 2006 Elsevier Ltd. All rights reserved.

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Poly(β-hydroxybutyrate), (PHB), is a biologically produced, biodegradable thennoplastic with commercial potential. In this work the qualitative and quantitative investigations of the structure and degradation of a previously unstudied, novel, fibrous form of PHB, were completed. This gel-spun PHB fibrous matrix, PHB(FM), which has a similar appearance to cotton wool, possesses a relatively complex structure which combines a large volume with a low mass and has potential for use as a wound scaffolding device. As a result of the intrinsic problems presented by this novel structure, a new experimental procedure was developed to analyze the degradation of the PHB to its monomer hydroxybutyric acid, (HBA). This procedure was used in an accelerated degradation model which accurately monitored the degradation of the undegraded and degraded fractions of a fibrous matrix and the degradation of its PHB component. The in vitro degradation mechanism was also monitored using phase contrast and scanning electron microscopy, differential scanning calorimetry, fibre diameter distributions and Fourier infra-red photoacoustic spectroscopy. The accelerated degradation model was used to predict the degradation of the samples in the physiological model and this provided a clearer picture as to the samples potential biodegradation as medical implantation devices. The degradation of the matrices was characterized by an initial penetration of the degradative medium and weakening of the fibre integrity due to cleavage of the ester linkages, this then led to the physical collapse of the fibres which increased the surface area to volume ratio of the sample and facilitated its degradation. Degradation in the later stages was reduced due to the experimental kinetics, compaction and degradation resistant material, most probably the highly crystalline regions of the PHB. The in vitro degradation of the PHB(FM) was influenced by blending with various polysaccharides, copolymerizing with poly(~-hydroxyvalerate), (PHV), and changes to the manufacturing process. The degradation was also detennined to be faster than that of conventional melt processed PHB based samples. It was concluded that the material factors such as processing, sample size and shape affected the degradation of PHB based samples with the major factor of sample surface area to volume ratio being of paramount importance in determining the degradation of a sample.

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This thesis documents the design, manufacture and testing of a passive and non-invasive micro-scale planar particle-from-fluid filter for segregating cell types from a homogeneous suspension. The microfluidics system can be used to separate spermatogenic cells from testis biopsy samples, providing a mechanism for filtrate retrieval for assisted reproduction therapy. The system can also be used for point-of-service diagnostics applications for hospitals, lab-on-a-chip pre-processing and field applications such as clinical testing in the third world. Various design concepts are developed and manufactured, and are assessed based on etched structure morphology, robustness to variations in the manufacturing process, and design impacts on fluid flow and particle separation characteristics. Segregation was measured using image processing algorithms that demonstrate efficiency is more than 55% for 1 µl volumes at populations exceeding 1 x 107. the technique supports a significant reduction in time over conventional processing, in the separation and identification of particle groups, offering a potential reduction in the associated cost of the targeted procedure. The thesis has developed a model of quasi-steady wetting flow within the micro channel and identifies the forces across the system during post-wetting equalisation. The model and its underlying assumptions are validated empirically in microfabricated test structures through a novel Micro-Particle Image Velocimetry technique. The prototype devices do not require ancillary equipment nor additional filtration media, and therefore offer fewer opportunities for sample contamination over conventional processing methods. The devices are disposable with minimal reagent volumes and process waste. Optimal processing parameters and production methods are identified with any improvements that could be made to enhance their performance in a number of identified potential applications.

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This thesis deals with the problems associated with the planning and control of production, with particular reference to a small aluminium die casting company. The main problem areas were identified as: (a) A need to be able to forecast the customers demands upon the company's facilities. (b) A need to produce a manufacturing programme in which the output of the foundry (or die casting section) was balanced with the available capacity in the machine shop. (c) The need to ensure that the resultant system enabled the company's operating budget to have a reasonable chance of being achieved. At the commencement of the research work the major customers were members of the automobile industry and had their own system of forecasting, from which they issued manufacturing schedules to their component suppliers, The errors in the forecast were analysed and the distributions noted. Using these distributions the customer's forecast was capable of being modified to enable his final demand to be met with a known degree of confidence. Before a manufacturing programme could be developed the actual manufacturing system had to be reviewed and it was found that as with many small companies there was a remarkable lack of formal control and written data. Relevant data with regards to the component and the manufacturing process had therefore to be collected and analysed. The foundry process was fixed but the secondary machining operations were analysed by a technique similar to Component Flow Analysis and as a result the machines were arranged in a series of flow lines. A system of manual production control was proposed and for comparison, a local computer bureau was approached and a system proposed incorporating the production of additional management information. These systems are compared and the relative merits discussed and a proposal made for implementation.

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The unmitigated transmission of undesirable vibration can result in problems by way of causing human discomfort, machinery and equipment failure, and affecting the quality of a manufacturing process. When identifiable transmission paths are discernible, vibrations from the source can be isolated from the rest of the system and this prevents or minimises the problems. The approach proposed here for vibration isolation is active force cancellation at points close to the vibration source. It uses force feedback for multiple-input and multiple-output control at the mounting locations. This is particularly attractive for rigid mounting of machine on relative flexible base where machine alignment and motions are to be restricted. The force transfer function matrix is used as a disturbance rejection performance specification for the design of MIMO controllers. For machine soft-mounted via flexible isolators, a model for this matrix has been derived. Under certain conditions, a simple multiplicative uncertainty model is obtained that shows the amount of perturbation a flexible base has on the machine-isolator-rigid base transmissibility matrix. Such a model is very suitable for use with robust control design paradigm. A different model is derived for the machine on hard-mounts without the flexible isolators. With this model, the level of force transmitted from a machine to a final mounting structure using the measurements for the machine running on another mounting structure can be determined. The two mounting structures have dissimilar dynamic characteristics. Experiments have verified the usefulness of the expression. The model compares well with other methods in the literature. The disadvantage lies with the large amount of data that has to be collected. Active force cancellation is demonstrated on an experimental rig using an AC industrial motor hard-mounted onto a relative flexible structure. The force transfer function matrix, determined from measurements, is used to design H and Static Output Feedback controllers. Both types of controllers are stable and robust to modelling errors within the identified frequency range. They reduce the RMS of transmitted force by between 30?80% at all mounting locations for machine running at 1340 rpm. At the rated speed of 1440 rpm only the static gain controller is able to provide 30?55% reduction at all locations. The H controllers on the other hand could only give a small reduction at one mount location. This is due in part to the deficient of the model used in the design. Higher frequency dynamics has been ignored in the model. This can be resolved by the use of a higher order model that can result in a high order controller. A low order static gain controller, with some tuning, performs better. But it lacks the analytical framework for analysis and design.

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The fate of vitamin E and the formation and identification of its transformation products were investigated at different stages of the manufacturing process of commercially produced cross-linked (by γ-irradiation) UHMWPE stabilised with vitamin E (vitamin E infused-post irradiation) used for tibia-components (as articulating surfaces) in total knee arthroplasty (total knee replacement). Vitamin E (α-tocopherol) and its transformation products were extracted from microtomed Tibia films and the different products were separated, isolated, purified using high performance liquid chromatography (HPLC), and characterised by spectroscopic methods and LC-MS. The amount of vitamin E and that of the products formed in the different Tibia samples and in their extracts were also quantified using FTIR and HPLC analysis and calibration curves. Thorough analysis of the Tibia extracts has shown that a number of vitamin E transformation products were formed at different concentrations at two selected stages of the implant manufacturing process that is before and after sterilisation by γ-irradiation. The identified products were found to correspond mainly to different stereoisomeric forms of a small number of vitamin E transformation products. Most of the observed products were of dimeric and trimeric nature with their identity confirmed through a detailed study of their spectral and chromatographic characteristics. It was found that the products of vitamin E, prior to the sterilisation step but after the crosslinking and doping of vitamin E, were mainly the dihydroxydimers and trimers (Tibia samples at this stage are referred to as “Tibia-VEPE”). After sterilisation and completion of the manufacturing process, additional dimers of vitamin E were also formed (Tibia samples at this stage are referred to as ‘Tibia-VEPE-Sterile’), Furthermore, two tocopherol-derived aldehydes (aldehyde 5-formyl-γ-tocopherol and aldehyde 7-formyl-γ-tocopherol) were also formed but at very low concentrations especially in the Tibia-VEPE-Sterile samples. The question of whether vitamin E becomes chemically reacted (grafted) onto the polymer matrix during the manufacturing process of the Tibia is also addressed.

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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.

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The aging responses of 2124 Al-SiC p metal matrix composite (MMC) and unreinforced matrix alloy are studied and related to variations in tensile properties. The MMC is aged from Wo starting conditions: (i) stretched and naturally aged and (ii) re-solution treated. Accelerated aging occurs in both MMC conditions compared with unreinforced alloy. Tensile strengths and elastic moduli are improved in the MMC compared with the alloy, but ductility is reduced. Stretched MMC exhibits higher strength but lower ductility and modulus than re-solutioned MMC. The re-solutioned MMC fails by microvoid coalescence in low aging conditions, and by void nucleation and shear in high aging conditions. Failure of the stretched MMC initiates at the surface at specimen shoulders, illustrating the increased notch sensitivity of this condition, and propagates via a zigzag shear fracture mode. Zigzag facet size increases on gross aging. Particle fracture occurs during tensile failure, but also before testing as a result of the manufacturing process. © 1995 The Institute of Materials.

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A wide range of metrology processes are involved in the manufacture of large products. In addition to the traditional tool-setting and product-verification operations, increasingly flexible metrology-enabled automation is also being used. Faced with many possible measurement problems and a very large number of metrology instruments employing diverse technologies, the selection of the appropriate instrument for a given task can be highly complex. Also, as metrology has become a key manufacturing process, it should be considered in the early stages of design, and there is currently very little research to support this. This paper provides an overview of the important selection criteria for typical measurement processes and presents some novel selection strategies. Metrics that can be used to assess measurability are also discussed. A prototype instrument selection and measurability analysis application is also presented, with discussion of how this can be used as the basis for development of a more sophisticated measurement planning tool. © 2010 Authors.

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Metrology processes used in the manufacture of large products include tool setting, product verification and flexible metrology enabled automation. The range of applications and instruments available makes the selection of the appropriate instrument for a given task highly complex. Since metrology is a key manufacturing process it should be considered in the early stages of design. This paper provides an overview of the important selection criteria for typical measurement processes and presents some novel selection strategies. Metrics which can be used to assess measurability are also discussed. A prototype instrument selection and measurability analysis application is presented with discussion of how this can be used as the basis for development of a more sophisticated measurement planning tool. © Springer-Verlag Berlin Heidelberg 2010.

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As levels of investment in advanced manufacturing systems increase, effective project management becomes ever more critical. This paper demonstrates how the model proposed by Mintzberg, Raisinghani and Theoret in 1976, which structures complicated strategic decision processes, can be applied to the design of new production systems for both descriptive and analytical research purposes. This paper sets a detailed case study concerning the design and development of an advanced manufacturing system within the Mintzberg decision model and so breaks down the decision sequence into constituent parts. It thus shows how a structured model can provide a framework for the researcher who wishes to study decision episodes in the design of manufacturing facilities in greater depth.