Caking behaviour of spray-dried milk powders:using scanning probe microscopy to study nanoscale surface properties and material composition

Spray drying is widely used to manufacture many powdered products, with the drying process parameters having significant influence over the final powder's surface properties and propensity for unwanted caking. In most cases caking experiments are performed on bulk powders, but especially in multi-component powders, it is often difficult to interpret these results, where interaction effects between particles can be complex. Here the technique of scanning probe microscopy is used to characterize the nanoscale properties of spray dried model milk powders in order to investigate the surface properties of the powders.

The practical challenges of servitized manufacture

Servitization is now widely recognised as the process of creating value by adding services to products. Since this term was first coined in the late 1980s it has been studied by a range of authors who have specifically sought to understand the methods and mechanisms of service-led competitive strategies for manufacturers. This paper reports on the experiences of a large company as they have moved towards servitized manufacture. This has been based on an extensive series of interviews with key personnel. The results of the study and implications for research are all reported.

Compressed orally disintegrating tablets:excipients evolution and formulation strategies

Introduction: Orally disintegrating tablets (ODTs) have emerged as one of the novel solid oral dosage forms with a potential to deliver a wide range of drug candidates to both paediatric and geriatric patient populations. Of the plethora of available technologies, compression of excipients offers a cost-effective and translatable methodology for the manufacture of ODTs. Areas covered: The review is a modest endeavour from the authors to assemble literature published over the last couple of decades on formulation development of compressed ODT. It describes the main ODT excipients used since the introduction of this dosage form in the 1990s and explores the switch from cellulose-based excipients towards sugar/polyols. Furthermore, it unfolds the key properties of ODT fillers, binders and disintegrants with an emphasis on their advantages and drawbacks. The review also provides a critical assessment of the various strategies employed for performance enhancement of compressed ODT with a focus on the underlying mechanisms for fast disintegration and acceptable mechanical strength. Expert opinion: Recent increase in the total number of compression-based technologies for ODT development promises to reduce the manufacturing cost of this dosage form in the future. However, some of the developed methods may affect the stability of tablets due to susceptibility to moisture, collapse of pores or the generation of less stable polymorphs which require rigorous testing prior to commercialization. © 2013 Informa UK, Ltd.

Diversifying into technical clothing manufacture:a situated learning theory perspective

An organisation’s ability to internalise external knowledge and learn from various sources in undertaking new product development and/or entering a new market is crucial to its competitive performance. Nevertheless, little attention has been paid to how growth-oriented small firms identify and exploit entrepreneurial opportunities, i.e. take entrepreneurial action, related to such methods of development, in a mature, contracting industry. The latter is particularly relevant to recent discussion and debate in academic and policy-making circles concerning the salvage of the clothing manufacture industry in developed industrialised countries, by intensifying efforts relating to diversification into high value manufacturing sectors. This paper, based on an instrumental case-firm, demonstrates analytically how learning as entrepreneurial action relating to diversifying into /technical clothing – i.e. a high value manufacturing/innovatory sector - takes place, drawing on situated learning theory. It is argued that learning relating to such entrepreneurial action is dynamic in nature and is founded on specific organising principles that foster both inter- and intracommunal learning.

Modular system design and control for flexible assembly

Flexible Assembly Systems (FASs) are normally associated with the automatic, or robotic, assembly of products, supported by automated material handling systems. However, manual assembly operations are still prevalent within many industries, where the complexity and variety of products prohibit the development of suitable automated assembly equipment. This article presents a generic model for incorporating flexibility into the design and control of assembly operations concerned with high variety/low volume manufacture, drawing on the principles for Flexible Manufacturing Systems (FMS) and Just-in-Time (JIT) delivery. It is based on work being undertaken in an electronics company where the assembly operations have been overhauled and restructured in response to a need for greater flexibility, shorter cycle times and reduced inventory levels. The principles employed are in themselves not original. However, the way they have been combined and tailored has created a total manufacturing control system which represents a new concept for responding to demands placed on market driven firms operating in an uncertain environment.

Saccharomyces Cerevisiae as a biotechnological tool for ageing research:studies on translation and metabolism

The yeast Saccharomyces cerevisiae is an important model organism for the study of cell biology. The similarity between yeast and human genes and the conservation of fundamental pathways means it can be used to investigate characteristics of healthy and diseased cells throughout the lifespan. Yeast is an equally important biotechnological tool that has long been the organism of choice for the production of alcoholic beverages, bread and a large variety of industrial products. For example, yeast is used to manufacture biofuels, lubricants, detergents, industrial enzymes, food additives and pharmaceuticals such as anti-parasitics, anti-cancer compounds, hormones (including insulin), vaccines and nutraceuticals. Its function as a cell factory is possible because of the speed with which it can be grown to high cell yields, the knowledge that it is generally recognized as safe (GRAS) and the ease with which metabolism and cellular pathways, such as translation can be manipulated. In this thesis, these two pathways are explored in the context of their biotechnological application to ageing research: (i) understanding translational processes during the high-yielding production of membrane protein drug targets and (ii) the manipulation of yeast metabolism to study the molecule, L-carnosine, which has been proposed to have anti-ageing properties. In the first of these themes, the yeast strains, spt3?, srb5?, gcn5? and yTHCBMS1, were examined since they have been previously demonstrated to dramatically increase the yields of a target membrane protein (the aquaporin, Fps1) compared to wild-type cells. The mechanisms underlying this discovery were therefore investigated. All high yielding strains were shown to have an altered translational state (mostly characterised by an initiation block) and constitutive phosphorylation of the translational initiation factor, eIF2a. The relevance of the initiation block was further supported by the finding that other strains, with known initiation blocks, are also high yielding for Fps1. A correlation in all strains between increased Fps1 yields and increased production of the transcriptional activator protein, Gcn4, suggested that yields are subject to translational control. Analysis of the 5´ untranslated region (UTR) of FPS1 revealed two upstream open reading frames (uORFs). Mutagenesis data suggest that high yielding strains may circumvent these control elements through either a leaky scanning or a re-initiation mechanism. In the second theme, the dipeptide L-carnosine (ß-alanyl-L-histidine) was investigated: it has previously been shown to inhibit the growth of cancer cells but delay senescence in cultured human fibroblasts and extend the lifespan of male fruit flies. To understand these apparently contradictory properties, the effects of L-carnosine on yeast were studied. S. cerevisiae can respire aerobically when grown on a non-fermentable carbon source as a substrate but has a respiro-fermentative metabolism when grown on a fermentable carbon source; these metabolisms mimic normal cell and cancerous cell metabolisms, respectively. When yeast were grown on fermentable carbon sources, in the presence of L-carnosine, a reduction in cell growth and viability was observed, which was not apparent for cells grown on a non-fermentable carbon source. The metabolism-dependent mechanism was confirmed in the respiratory yeast species Pichia pastoris. Further analysis of S. cerevisiae yeast strains with deletions in their nutrient-sensing pathway, which result in an increase in respiratory metabolism, confirmed the metabolism-dependent effects of L-carnosine.

Fiber bragg gratings:advances in fabrication process and tools

Successful commercialization of a technology such as Fiber Bragg Gratings requires the ability to manufacture devices repeatably, quickly and at low cost. Although the first report of photorefractive gratings was in 1978 it was not until 1993, when phase mask fabrication was demonstrated, that this became feasible. More recently, draw tower fabrication on a production level and grating writing through the polymer jacket have been realized; both important developments since they preserve the intrinsic strength of the fiber. Potentially the most significant recent development has been femtosecond laser inscription of gratings. Although not yet a commercial technology, it provides the means of writing multiple gratings in the optical core providing directional sensing capability in a single fiber. Femtosecond processing can also be used to machine the fiber to produce micronscale slots and holes enhancing the interaction between the light in the core and the surrounding medium. © 2011 Bentham Science Publishers Ltd. All rights reserved.

Composite cell support membranes based on collagen and polycaprolactone for tissue engineering of skin

The preparation and characterisation of collagen:PCL composites for manufacture of tissue engineered skin substitutes and models are reported. Films having collagen:PCL (w/w) ratios of 1:4, 1:8 and 1:20 were prepared by impregnation of lyophilised collagen mats by PCL solutions followed by solvent evaporation. In vitro assays of collagen release and residual collagen content revealed an expected inverse relationship between the collagen release rate and the content of synthetic polymer in the composite that may be exploited for controlled presentation and release of biopharmaceuticals such as growth factors. DSC analysis revealed the characteristic melting point of PCL at around 60°C and a tendency for the collagen component, at high loading, to impede crystallinity development within the PCL phase. The preparation of fibroblast/composite constructs was investigated using cell culture as a first stage in mimicking the dermal/epidermal structure of skin. Fibroblasts were found to attach and proliferate on all the composites investigated reaching a maximum of 2×105/cm2 on 1:20 collagen:PCL materials at day 8 with cell numbers declining thereafter. Keratinocyte growth rates were similar on all types of collagen:PCL materials investigated reaching a maximum of 6.6×104/cm2 at day 6. The results revealed that composite films of collagen and PCL are favourable substrates for growth of fibroblasts and keratinocytes and may find utility for skin repair. © 2003 Elsevier Ltd. All rights reserved.

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.

Catalysing sustainable fuel and chemical synthesis

Concerns over the economics of proven fossil fuel reserves, in concert with government and public acceptance of the anthropogenic origin of rising CO2 emissions and associated climate change from such combustible carbon, are driving academic and commercial research into new sustainable routes to fuel and chemicals. The quest for such sustainable resources to meet the demands of a rapidly rising global population represents one of this century’s grand challenges. Here, we discuss catalytic solutions to the clean synthesis of biodiesel, the most readily implemented and low cost, alternative source of transportation fuels, and oxygenated organic molecules for the manufacture of fine and speciality chemicals to meet future societal demands.

Exploring the digital supply chain:implications and models for online software distribution

As a discipline, supply chain management (SCM) has traditionally been primarily concerned with the procurement, processing, movement and sale of physical goods. However an important class of products has emerged - digital products - which cannot be described as physical as they do not obey commonly understood physical laws. They do not possess mass or volume, and they require no energy in their manufacture or distribution. With the Internet, they can be distributed at speeds unimaginable in the physical world, and every copy produced is a 100% perfect duplicate of the original version. Furthermore, the ease with which digital products can be replicated has few analogues in the physical world. This paper assesses the effect of non-physicality on one such product – software – in relation to the practice of SCM. It explores the challenges that arise when managing the software supply chain and how practitioners are addressing these challenges. Using a two-pronged exploratory approach that examines the literature around software management as well as direct interviews with software distribution practitioners, a number of key challenges associated with software supply chains are uncovered, along with responses to these challenges. This paper proposes a new model for software supply chains that takes into account the non-physicality of the product being delivered. Central to this model is the replacement of physical flows with flows of intellectual property, the growing importance of innovation over duplication and the increased centrality of the customer in the entire process. Hybrid physical / digital supply chains are discussed and a framework for practitioners concerned with software supply chains is presented.

Diversifying into technical clothing manufacture as entrepreneurial learning:a situated learning theory perspective

Purpose - The purpose of this paper is to demonstrate analytically how entrepreneurial action as learning relating to diversifying into technical clothing - i.e. a high-value manufacturing sector - can take place. This is particularly relevant to recent discussion and debate in academic and policy-making circles concerning the survival of the clothing manufacture industry in developed industrialised countries. Design/methodology/approach - Using situated learning theory (SLT) as the major analytical lens, this case study examines an episode of entrepreneurial action relating to diversification into a high-value manufacturing sector. It is considered on instrumentality grounds, revealing wider tendencies in the management of knowledge and capabilities requisite for effective entrepreneurial action of this kind. Findings - Boundary events, brokers, boundary objects, membership structures and inclusive participation that addresses power asymmetries are found to be crucial organisational design elements, enabling the development of inter- and intracommunal capacities. These together constitute a dynamic learning capability, which underpins entrepreneurial action, such as diversification into high-value manufacturing sectors. Originality/value - Through a refinement of SLT in the context of entrepreneurial action, the paper contributes to an advancement of a substantive theory of managing technological knowledge and capabilities for effective diversification into high-value manufacturing sectors. Copyright © 2014 Emerald Group Publishing Limited. All rights reserved.

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.

Microfluidic-controlled manufacture of liposomes for the solubilisation of a poorly water soluble drug

Besides their well-described use as delivery systems for water-soluble drugs, liposomes have the ability to act as a solubilizing agent for drugs with low aqueous solubility. However, a key limitation in exploiting liposome technology is the availability of scalable, low-cost production methods for the preparation of liposomes. Here we describe a new method, using microfluidics, to prepare liposomal solubilising systems which can incorporate low solubility drugs (in this case propofol). The setup, based on a chaotic advection micromixer, showed high drug loading (41 mol%) of propofol as well as the ability to manufacture vesicles with at prescribed sizes (between 50 and 450 nm) in a high-throughput setting. Our results demonstrate the ability of merging liposome manufacturing and drug encapsulation in a single process step, leading to an overall reduced process time. These studies emphasise the flexibility and ease of applying lab-on-a-chip microfluidics for the solubilisation of poorly water-soluble drugs.

The translation of cell-based therapies:clinical landscape and manufacturing challenges

Cell-based therapies have the potential to make a large contribution toward currently unmet patient need and thus effective manufacture of these products is essential. Many challenges must be overcome before this can become a reality and a better definition of the manufacturing requirements for cell-based products must be obtained. The aim of this study is to inform industry and academia of current cell-based therapy clinical development and to identify gaps in their manufacturing requirements. A total of 1342 active cell-based therapy clinical trials have been identified and characterized based on cell type, target indication and trial phase. Multiple technologies have been assessed for the manufacture of these cell types in order to facilitate product translation and future process development.