The influence of formulation and manufacturing process parameters on the characteristics of lyophilized orally disintegrating tablets

Gelatin is a principal excipient used as a binder in the formulation of lyophilized orally disintegrating tablets. The current study focuses on exploiting the physicochemical properties of gelatin by varying formulation parameters to determine their influence on orally disintegrating tablet (ODT) characteristics. Process parameters, namely pH and ionic strength of the formulations, and ball milling were investigated to observe their effects on excipient characteristics and tablet formation. The properties and characteristics of the formulations and tablets which were investigated included: glass transition temperature, wettability, porosity, mechanical properties, disintegration time, morphology of the internal structure of the freeze-dried tablets, and drug dissolution. The results from the pH study revealed that adjusting the pH of the formulation away from the isoelectric point of gelatin, resulted in an improvement in tablet disintegration time possibly due to increase in gelatin swelling resulting in greater tablet porosity. The results from the ionic strength study revealed that the inclusion of sodium chloride influenced tablet porosity, tablet morphology and the glass transition temperature of the formulations. Data from the milling study showed that milling the excipients influenced formulation characteristics, namely wettability and powder porosity. The study concludes that alterations of simple parameters such as pH and salt concentration have a significant influence on formulation of ODT. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

The opportunity recognition process:the mechanisms by which entrepreneurial opportunities are recognised and the role played by social networks in this process

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Multi-level visualisation using Gaussian process latent variable models

Projection of a high-dimensional dataset onto a two-dimensional space is a useful tool to visualise structures and relationships in the dataset. However, a single two-dimensional visualisation may not display all the intrinsic structure. Therefore, hierarchical/multi-level visualisation methods have been used to extract more detailed understanding of the data. Here we propose a multi-level Gaussian process latent variable model (MLGPLVM). MLGPLVM works by segmenting data (with e.g. K-means, Gaussian mixture model or interactive clustering) in the visualisation space and then fitting a visualisation model to each subset. To measure the quality of multi-level visualisation (with respect to parent and child models), metrics such as trustworthiness, continuity, mean relative rank errors, visualisation distance distortion and the negative log-likelihood per point are used. We evaluate the MLGPLVM approach on the ‘Oil Flow’ dataset and a dataset of protein electrostatic potentials for the ‘Major Histocompatibility Complex (MHC) class I’ of humans. In both cases, visual observation and the quantitative quality measures have shown better visualisation at lower levels.

Land use change and the planning process in historic town centres

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

An investigation of the direct extrusion process with the application of oscillatory energy

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Representing the assessment process for psychodynamic psychotherapy within a computerized model of human classification

This research describes a computerized model of human classification which has been constructed to represent the process by which assessments are made for psychodynamic psychotherapy. The model assigns membership grades (MGs) to clients so that the most suitable ones have high values in the therapy category. Categories consist of a hierarchy of components, one of which, ego strength, is analysed in detail to demonstrate the way it has captured the psychotherapist's knowledge. The bottom of the hierarchy represents the measurable factors being assessed during an interview. A questionnaire was created to gather the identified information and was completed by the psychotherapist after each assessment. The results were fed into the computerized model, demonstrating a high correlation between the model MGs and the suitability ratings of the psychotherapist (r = .825 for 24 clients). The model has successfully identified the relevant data involved in assessment and simulated the decision-making process of the expert. Its cognitive validity enables decisions to be explained, which means that it has potential for therapist training and also for enhancing the referral process, with benefits in cost effectiveness as well as in the reduction of trauma to clients. An adapted version measuring client improvement would give quantitative evidence for the benefit of therapy, thereby supporting auditing and accountability. © 1997 The British Psychological Society.

Measures of process harmonization

Context Many large organizations juggle an application portfolio that contains different applications that fulfill similar tasks in the organization. In an effort to reduce operating costs, they are attempting to consolidate such applications. Before consolidating applications, the work that is done with these applications must be harmonized. This is also known as process harmonization. Objective The increased interest in process harmonization calls for measures to quantify the extent to which processes have been harmonized. These measures should also uncover the factors that are of interest when harmonizing processes. Currently, such measures do not exist. Therefore, this study develops and validates a measurement model to quantify the level of process harmonization in an organization. Method The measurement model was developed by means of a literature study and structured interviews. Subsequently, it was validated through a survey, using factor analysis and correlations with known related constructs. Results As a result, a valid and reliable measurement model was developed. The factors that are found to constitute process harmonization are: the technical design of the business process and its data, the resources that execute the process, and the information systems that are used in the process. In addition, strong correlations were found between process harmonization and process standardization and between process complexity and process harmonization. Conclusion The measurement model can be used by practitioners, because it shows them the factors that must be taken into account when harmonizing processes, and because it provides them with a means to quantify the extent to which they succeeded in harmonizing their processes. At the same time, it can be used by researchers to conduct further empirical research in the area of process harmonization.

Expansion, harvest and cryopreservation of human mesenchymal stem cells in a serum-free microcarrier process

Human mesenchymal stem cell (hMSC) therapies are currently progressing through clinical development, driving the need for consistent, and cost effective manufacturing processes to meet the lot-sizes required for commercial production. The use of animal-derived serum is common in hMSC culture but has many drawbacks such as limited supply, lot-to-lot variability, increased regulatory burden, possibility of pathogen transmission, and reduced scope for process optimization. These constraints may impact the development of a consistent large-scale process and therefore must be addressed. The aim of this work was therefore to run a pilot study in the systematic development of serum-free hMSC manufacturing process. Human bone-marrow derived hMSCs were expanded on fibronectin-coated, non-porous plastic microcarriers in 100mL stirred spinner flasks at a density of 3×10⁵cells.mL^-1 in serum-free medium. The hMSCs were successfully harvested by our recently-developed technique using animal-free enzymatic cell detachment accompanied by agitation followed by filtration to separate the hMSCs from microcarriers, with a post-harvest viability of 99.63±0.03%. The hMSCs were found to be in accordance with the ISCT characterization criteria and maintained hMSC outgrowth and colony-forming potential. The hMSCs were held in suspension post-harvest to simulate a typical pooling time for a scaled expansion process and cryopreserved in a serum-free vehicle solution using a controlled-rate freezing process. Post-thaw viability was 75.8±1.4% with a similar 3h attachment efficiency also observed, indicating successful hMSC recovery, and attachment. This approach therefore demonstrates that once an hMSC line and appropriate medium have been selected for production, multiple unit operations can be integrated to generate an animal component-free hMSC production process from expansion through to cryopreservation.

A Note on the Asymptotic Behaviour of a Periodic Multitype Galton-Watson Branching Process

2000 Mathematics Subject Classification: 60J80.

Manufacturing process challenges when machining superalloys

The implementation of advanced manufacturing systems with high process capability is an essential requirement for the high value manufacturing industries. To ensure high process capability, industry needs to deal with the requirement for tight tolerances and the unavoidable variations in materials, and manufacturing and inspection processes. In the case of machining superalloys, such variations result in the need to change the machine parameters for producing different batches of materials from different suppliers. This is required in order to get the process under control and reduce waste and defects, leading to better competitiveness. This papers discuss the variability in materials and the corresponding process requirements when machining superalloys, and highlights the impact of metrology in achieving manufacturing process improvement.

Weak Ergodicity of Mt /Mt /N /N + R Queue

2000 Mathematics Subject Classification: 60J27, 60K25.

Serum-free process development:improving the yield and consistency of human mesenchymal stromal cell production

Background aims: The cost-effective production of human mesenchymal stromal cells (hMSCs) for off-the-shelf and patient specific therapies will require an increasing focus on improving product yield and driving manufacturing consistency. Methods: Bone marrow-derived hMSCs (BM-hMSCs) from two donors were expanded for 36 days in monolayer with medium supplemented with either fetal bovine serum (FBS) or PRIME-XV serum-free medium (SFM). Cells were assessed throughout culture for proliferation, mean cell diameter, colony-forming potential, osteogenic potential, gene expression and metabolites. Results: Expansion of BM-hMSCs in PRIME-XV SFM resulted in a significantly higher growth rate (P < 0.001) and increased consistency between donors compared with FBS-based culture. FBS-based culture showed an inter-batch production range of 0.9 and 5 days per dose compared with 0.5 and 0.6 days in SFM for each BM-hMSC donor line. The consistency between donors was also improved by the use of PRIME-XV SFM, with a production range of 0.9 days compared with 19.4 days in FBS-based culture. Mean cell diameter has also been demonstrated as a process metric for BM-hMSC growth rate and senescence through a correlation (R² = 0.8705) across all conditions. PRIME-XV SFM has also shown increased consistency in BM-hMSC characteristics such as per cell metabolite utilization, in vitro colony-forming potential and osteogenic potential despite the higher number of population doublings. Conclusions: We have increased the yield and consistency of BM-hMSC expansion between donors, demonstrating a level of control over the product, which has the potential to increase the cost-effectiveness and reduce the risk in these manufacturing processes.

Estimation of a Regression Function on a Point Process and its Application to Financial Ruin Risk Forecast

2000 Mathematics Subject Classification: Primary 60G55; secondary 60G25.

To what extent and in what manner do Chinese and Indian contract research organisation learn and upgrade with the unbundling the global pharmaceutical R&D value chain?

The paper applies the GVC framework to analyse the organisational and geographical reconfiguration of the global R&D function of leading US and European pharmaceutical MNCs. Though pharmaceutical MNCs have been outsourcing clinical trial activities since the mid-1990s, the outsourcing of discovery research tasks is a phenomenon of the 2000s (Ramirez 2013). Moreover, in the context of a crisis of R&D productivity and increasing pressure from shareholders, a number of US and European pharmaceutical MNCs are breaking up their R&D function in an attempt to increase flexibility and reduce risk as well as costs and are thereby restructuring the global architecture of their R&D function. This break-up, or unbundling (Sako 2006), of the R&D function is particularly interesting given the prevalence of market failure in innovation (Howells et al 2008), the non-modular nature of the R&D process in this industry (Pisano 2006) and the strategic important of this activity to the core competence and long-term competitive advantage of firms in this sector. The focus of this paper is on the outsourcing of R&D activities to Chinese and Indian independently-owned contract research organisations (CROs) and the way these firms are becoming integrated as service providers into the global R&D function (or R&D value chain) of pharmaceutical MNCs. Above all the paper is concerned with the development of capabilities of CROs from these two countries and the dynamics of upgrading in GVCs in knowledge-intensive functions. The paper therefore discusses the role of both knowledge flows within global pharmaceutical R&D value chains as well as national innovation systems on the development of capabilities of Chinese and Indian CROs. Our analysis is based on data from semi-structured interviews collected from senior R&D managers from a sample of ten US and European pharmaceutical MNCs and owners and senior R&D managers from five Chinese and five Indian CROs who are providing research services to MNCs in this industry. We discuss the emergence of R&D outsourcing in this industry and the nature and mechanisms of knowledge flows within R&D value chains. The embeddedness of CROS in the national innovation systems of their home countries is also discussed.