Freezing process optimisation of pharmaceutical formulations for freeze drying

The body of work presented in this thesis are in three main parts: [1] the effect of ultrasound on freezing events of ionic systems, [2] the importance of formulation osmolality in freeze drying, and [3] a novel system for increasing primary freeze drying rate. Chapter 4 briefly presents the work on method optimisation, which is still very much in its infancy. Aspects of freezing such as nucleation and ice crystal growth are strongly related with ice crystal morphology; however, the ice nucleation process typically occurs in a random, non-deterministic and spontaneous manner. In view of this, ultrasound, an emerging application in pharmaceutical sciences, has been applied to aid in the acceleration of nucleation and shorten the freezing process. The research presented in this thesis aimed to study the effect of sonication on nucleation events in ionic solutions, and more importantly how sonication impacts on the freezing process. This work confirmed that nucleation does occur in a random manner. It also showed that ultrasonication aids acceleration of the ice nucleation process and increases the freezing rate of a solution. Cryopreservation of animal sperm is an important aspect of breeding in animal science especially for endangered species. In order for sperm cryopreservation to be successful, cryoprotectants as well as semen extenders are used. One of the factors allowing semen preservation media to be optimum is the osmolality of the semen extenders used. Although preservation of animal sperm has no relation with freeze drying of pharmaceuticals, it was used in this thesis to make a case for considering the osmolality of a formulation (prepared for freeze drying) as a factor for conferring protein protection against the stresses of freeze drying. The osmolalities of some common solutes (mostly sugars) used in freeze drying were determined (molal concentration from 0.1m to 1.2m). Preliminary investigation on the osmolality and osmotic coefficients of common solutes were carried out. It was observed that the osmotic coefficient trend for the sugars analysed could be grouped based on the types of sugar they are. The trends observed show the need for further studies to be carried out with osmolality and to determine how it may be of importance to protein or API protection during freeze drying processes. Primary drying is usually the longest part of the freeze drying process, and primary drying times lasting days or even weeks are not uncommon; however, longer primary drying times lead to longer freeze drying cycles, and consequently increased production costs. Much work has been done previously by others using different processes (such as annealing) in order to improve primary drying times; however, these do not come without drawbacks. A novel system involving the formation of a frozen vial system which results in the creation of a void between the formulation and the inside wall of a vial has been devised to increase the primary freeze drying rate of formulations without product damage. Although the work is not nearly complete, it has been shown that it is possible to improve and increase the primary drying rate of formulations without making any modifications to existing formulations, changing storage vials, or increasing the surface area of freeze dryer shelves.

A patient's perspective:the impact of adverse drug reactions on patients and their views on reporting

What is known and objective: Adverse drug reactions to prescribed medication are relatively common events. However, the impact such reactions have on patients and their attitude to reporting such events have only been poorly explored. Previous studies relying on self-reporting patients indicate that altruism is an important factor. In the United Kingdom, patient reporting started in 2005; though, numbers of serious reports remain low. Method: A purposive sample of fifteen patients who had been admitted to an inner city hospital with an adverse drug reaction were interviewed using a semi-structured questionnaire. Patients were asked to relate in their own words their experience of an adverse drug reaction. Patient's reactions to the information leaflet, adherence to treatment and use of other sources of information on medication were assessed. Interviews were recorded, and a thematic analysis of patients'responses was performed. Results and discussion: Analysis of the patient interviews demonstrated the reality of being admitted to hospital is often a frightening process with a significant emotional cost. Anger, isolation, resentment and blame were common factors, particularly when medicines had been prescribed for acute conditions. For patients with chronic conditions, a more phlegmatic approach was seen especially with conditions with a strong support networks. Patients felt that communication and information should have been more readily available from the health care professional who prescribed the medication, although few had read the patient information leaflet. Only a minority of patients linked the medication they had taken to the adverse event, although some had received false reassurance that the drug was not related to their illness creating additional barriers. In contrast to previous studies, many patients felt that adverse drug reporting was not their concern, particularly as they obtained little direct benefit from it. The majority of patients were unaware of the Yellow Card Scheme in the UK for patient reporting. Even when explained, the scheme was felt too cold and impersonal and not a patient's 'job'. What is new and conclusion: Patients having a severe adverse drug reaction following an acute illness felt negative emotions towards their health care provider. Those with a chronic condition rationalized the event and coped better with its impact. Neither group felt that reporting the adverse reaction was their responsibility. Encouraging patients to report remains important but expecting patients to report solely for altruistic purposes may be unrealistic. © 2011 Blackwell Publishing Ltd.

Microstructure-based inherent anisotropy of asphalt mixtures

Asphalt mixtures have been demonstrated to be anisotropic materials in both laboratory and field tests. The anisotropy of asphalt mixtures consists of inherent anisotropy and stress-induced anisotropy. In previous work, the inherent anisotropy of asphalt mixtures was quantified by using only the inclination angles of the coarse aggregate particles in the asphalt mixtures. However, the inclination of fine aggregates also has a contribution to the inherent anisotropy. Moreover, the contribution to the inherent anisotropy of each aggregate may not be the same as in the previous work but will depend on the size, orientation, and sphericity of the aggregate particle. This paper quantifies the internal microstructure of the aggregates in asphalt mixtures by using an aggregate-related geometric parameter, the vector magnitude. The original formulation of the vector magnitude, which addresses only the orientation of coarse aggregates, is modified to account for not only the coarse aggregate orientation, but also the size, orientation, and sphericity of coarse and fine aggregates. This formulation is applied to cylindrical lab-mixed lab-compacted asphalt mixture specimens varying in asphalt binder type, air void content, and aging period. The vertical modulus and the horizontal modulus are also measured by using nondestructive tests. A relationship between the modified vector magnitude and the modulus ratio of the vertical modulus to the horizontal modulus is developed to quantify the influence of the inherent microstructure of the aggregates on the anisotropy of the mixtures. The modulus ratio is found to depend solely on the aggregate characteristics including the inclination angle, size, and sphericity, and it is independent of the asphalt binder type, air void content, and aging period. The inclination angle, itself, proves to be insufficient to quantify the inherent anisotropy of the asphalt mixtures. © 2011 American Society of Civil Engineers.

Efficiency of regenerative schemes

We explore the efficiency of various regeneration schemes in communication systems. We discuss new efficient schemes for multilevel phase and amplitude regeneration and illustrate it on example of 16-symbol constellations. © 2014 IEEE.

The Post-Growth Project:how the end of economic growth could bring a fairer and happier society

This book challenges the assumption that it is bad news when the economy doesn’t grow. For decades, it has been widely recognized that there are ecological limits to continuing economic growth and that different ways of living, working and organizing our economies are urgently required. This urgency has increased since the financial crash of 2007–2008, but mainstream economists and politicians are unable to think differently. The authors of this book demonstrate why our economic system demands ecologically unsustainable growth and the pursuit of more ‘stuff’. They believe that what matters is quality, not quantity – a better life based on having fewer material possessions, less production and less work. Such a way of life will emphasize well‑being, community, security and ‘conviviality’. That is, more real wealth. The book will therefore appeal to everyone curious as to how a new post-growth economics can be conceived and enacted. It will be of particular interest to policy makers, politicians, businesspeople, trade unionists, academics, students, journalists and a wide range of people working in the not-for-profit sector. All of the contributors are leading thinkers on green issues and members of the new think-tank Green House.

Large-scale complex IT systems

Society depends on complex IT systems created by integrating and orchestrating independently managed systems. The incredible increase in scale and complexity in them over the past decade means new software-engineering techniques are needed to help us cope with their inherent complexity. The key characteristic of these systems is that they are assembled from other systems that are independently controlled and managed. While there is increasing awareness in the software engineering community of related issues, the most relevant background work comes from systems engineering. The interacting algos that led to the Flash Crash represent an example of a coalition of systems, serving the purposes of their owners and cooperating only because they have to. The owners of the individual systems were competing finance companies that were often mutually hostile. Each system jealously guarded its own information and could change without consulting any other system.

Synergistic synthesis of quasi-monocrystal CdS nanoboxes with high-energy facets

Hollow nanostructures with a highly oriented lattice structure and active facets are promising for catalytic applications, while their preparation via traditional approaches contains multiple steps and is time and energy consuming. Here, we demonstrate a new one-step strategy involving two complementary reactions which promote each other; it is capable of producing unique hollow nanoparticles. Specifically, we apply synergic cooperation of cation exchange and chemical etching to attack PbS nanosized cubes (NCs) and produce CdS quasi-monocrystal nanoboxes (QMNBs) which possess the smallest dimensions reported so far, a metastable zinc-blende phase, a large specific surface area, and particularly high-energy {100} facets directly visualized by aberration-corrected scanning transmission electron microscopy. These properties in combination allow the nanoboxes to acquire exceptional photocatalytic activities. As an extension of the approach, we use the same strategy to prepare Co9S8 and Cu7.2S4 single-crystal hollow nanooctahedrons (SCHNOs) successfully. Hence, the synergic reaction synthesis strategy exhibits great potential in engineering unique nanostructures with superior properties.

Handling high level of censoring for endovascular aortic repair risk prediction

Feature selection is important in medical field for many reasons. However, selecting important variables is a difficult task with the presence of censoring that is a unique feature in survival data analysis. This paper proposed an approach to deal with the censoring problem in endovascular aortic repair survival data through Bayesian networks. It was merged and embedded with a hybrid feature selection process that combines cox's univariate analysis with machine learning approaches such as ensemble artificial neural networks to select the most relevant predictive variables. The proposed algorithm was compared with common survival variable selection approaches such as; least absolute shrinkage and selection operator LASSO, and Akaike information criterion AIC methods. The results showed that it was capable of dealing with high censoring in the datasets. Moreover, ensemble classifiers increased the area under the roc curves of the two datasets collected from two centers located in United Kingdom separately. Furthermore, ensembles constructed with center 1 enhanced the concordance index of center 2 prediction compared to the model built with a single network. Although the size of the final reduced model using the neural networks and its ensembles is greater than other methods, the model outperformed the others in both concordance index and sensitivity for center 2 prediction. This indicates the reduced model is more powerful for cross center prediction.

Influence of cutting parameters and tool wear on martensitic stainless steel surface integrity after a face milling process

Surface finish is one of the most relevant aspects of machining operations, since it is one of the principle methods to assess quality. Also, surface finish influences mechanical properties such as fatigue behavior, wear, corrosion, etc. The feed, the cutting speed, the cutting tool material, the workpiece material and the cutting tool wear are some of the most important factors that affects the surface roughness of the machined surface. Due to the importance of the martensitic 416 stainless steel in the petroleum industry, especially in valve parts and pump shafts, this material was selected to study the influence of the feed per tooth and cutting speed on tool wear and surface integrity. Also the influence of tool wear on surface roughness is analyzed. Results showed that high values of roughness are obtained when using low cutting speed and feed per tooth and by using these conditions tool wear decreases prolonging tool life. Copyright © 2009 by ASME.