From Polymorph Screening to Dissolution Testing - Solid Phase Analysis during Pharmaceutical Development and Manufacturing

Solid materials can exist in different physical structures without a change in chemical composition. This phenomenon, known as polymorphism, has several implications on pharmaceutical development and manufacturing. Various solid forms of a drug can possess different physical and chemical properties, which may affect processing characteristics and stability, as well as the performance of a drug in the human body. Therefore, knowledge and control of the solid forms is fundamental to maintain safety and high quality of pharmaceuticals. During manufacture, harsh conditions can give rise to unexpected solid phase transformations and therefore change the behavior of the drug. Traditionally, pharmaceutical production has relied on time-consuming off-line analysis of production batches and finished products. This has led to poor understanding of processes and drug products. Therefore, new powerful methods that enable real time monitoring of pharmaceuticals during manufacturing processes are greatly needed. The aim of this thesis was to apply spectroscopic techniques to solid phase analysis within different stages of drug development and manufacturing, and thus, provide a molecular level insight into the behavior of active pharmaceutical ingredients (APIs) during processing. Applications to polymorph screening and different unit operations were developed and studied. A new approach to dissolution testing, which involves simultaneous measurement of drug concentration in the dissolution medium and in-situ solid phase analysis of the dissolving sample, was introduced and studied. Solid phase analysis was successfully performed during different stages, enabling a molecular level insight into the occurring phenomena. Near-infrared (NIR) spectroscopy was utilized in screening of polymorphs and processing-induced transformations (PITs). Polymorph screening was also studied with NIR and Raman spectroscopy in tandem. Quantitative solid phase analysis during fluidized bed drying was performed with in-line NIR and Raman spectroscopy and partial least squares (PLS) regression, and different dehydration mechanisms were studied using in-situ spectroscopy and partial least squares discriminant analysis (PLS-DA). In-situ solid phase analysis with Raman spectroscopy during dissolution testing enabled analysis of dissolution as a whole, and provided a scientific explanation for changes in the dissolution rate. It was concluded that the methods applied and studied provide better process understanding and knowledge of the drug products, and therefore, a way to achieve better quality.

Socioeconomic Status, Occupational Factors and Lifestyle as Predictors of Hospitalisation for Back Disorders

The aim of this dissertation was to examine the determinants of severe back disorders leading to hospital admission in Finland. First, back-related hospitalisations were considered from the perspective of socioeconomic status, occupation, and industry. Secondly, the significance of psychosocial factors at work, sleep disturbances, and such lifestyle factors as smoking and overweight was studied as predictors of hospitalisation due to back disorders. Two sets of data were used: 1) the population-based data comprised all occupationally active Finns aged 25-64, and included hospitalisations due to back disorders in 1996 and 2) a cohort of employees followed up from 1973 to 2000 having been hospitalised due to back disorders. The results of the population-based study showed that people in physically strenuous industries and occupations, such as agriculture and manufacturing, were at an increased risk of being hospitalised for back disorders. The lowest hospitalisation rates were found in sedentary occupations. Occupational class and the level of formal education were independently associated with hospitalisation for back disorders. This stratification was fairly consistent across age-groups and genders. Men had a slightly higher risk of becoming hospitalised compared with women, and the risk increased with age among both genders. The results of the prospective cohort study showed that psychosocial factors at work such as low job control and low supervisor support predicted subsequent hospitalisation for back disorders even when adjustments were made for occupational class and physical workload history. However, psychosocial factors did not predict hospital admissions due to intervertebral disc disorders; only admissions due to other back disorders. Smoking and overweight predicted, instead, only hospitalisation for intervertebral disc disorders. These results suggest that the etiological factors of disc disorders and other back disorders differ from each other. The study concerning the association of sleep disturbances and other distress symptoms with hospitalisation for back disorders revealed that sleep disturbances predicted subsequent hospitalisation for all back disorders after adjustment for chronic back disorders and recurrent back symptoms at baseline, as well as for work-related load and lifestyle factors. Other distress symptoms were not predictive of hospitalisation.

Use of biomass fuels in the brick-making industries of Sudan: Implications for deforestation and greenhouse gas emission

The study focuses on the potential roles of the brick making industries in Sudan in deforestation and greenhouse gas emission due to the consumption of biofuels. The results were based on the observation of 25 brick making industries from three administrative regions in Sudan namely, Khartoum, Kassala and Gezira. The methodological approach followed the procedures outlined by the Intergovernmental Panel on Climate Change (IPCC). For predicting a serious deforestation scenario, it was also assumed that all of wood use for this particular purpose is from unsustainable sources. The study revealed that the total annual quantity of fuelwood consumed by the surveyed brick making industries (25) was 2,381 t dm. Accordingly, the observed total potential deforested wood was 10,624 m3, in which the total deforested round wood was 3,664 m3 and deforested branches was 6,961 m3. The study observed that a total of 2,990 t biomass fuels (fuelwood and dung cake) consumed annually by the surveyed brick making industries for brick burning. Consequently, estimated total annual emissions of greenhouse gases were 4,832 t CO2, 21 t CH4, 184 t CO, 0.15 t N20, 5 t NOX and 3.5 t NO while the total carbon released in the atmosphere was 1,318 t. Altogether, the total annual greenhouse gases emissions from biomass fuels burning was 5,046 t; of which 4,104 t from fuelwood and 943 t from dung cake burning. According to the results, due to the consumption of fuelwood in the brick making industries (3,450 units) of Sudan, the amount of wood lost from the total growing stock of wood in forests and trees in Sudan annually would be 1,466,000 m3 encompassing 505,000 m3 round wood and 961,000 m3 branches annually. By considering all categories of biofuels (fuelwood and dung cake), it was estimated that, the total emissions from all the brick making industries of Sudan would be 663,000 t CO2, 2,900 t CH4, 25,300 t CO, 20 t N2O, 720 t NOX and 470 t NO per annum, while the total carbon released in the atmosphere would be 181,000 t annually.

The Structure and Short-Term Development of Finnish Industries in the 1920s and 1930s : An Input-output Approach

Tutkimuksen tavoitteena on tuottaa uutta tietoa Suomen kansantalouden rakenteesta ja lyhyen aikavälin kehityksestä 1920- ja 1930-luvulla. Tutkimus toteutettiin laatimalla kansantaloutta kuvaava panos-tuotostaulu vuodelle 1928 sekä sen laajennus, panos-tuotosmalli. Aineiston avulla kuvataan kansantalouden rakenteellisia riippuvuuksia, tuotannon avaintoimialoja sekä näiden vaikutusta kansantalouteen. Lisäksi tutkimuksessa tarkastellaan kansantalouden tuontiriippuvuutta sekä tuontitullien vaikutusta hintoihin 1930-luvun laman aikana. Tutkimuksen perusteella voitiin identifioida Suomen kansantalouden avaintoimialat vuonna 1928: maatalous, metsätalous, elintarviketeollisuus, puuteollisuus, paperiteollisuus ja rakennustoiminta. Erityisesti elintarviketeollisuuden vahva rooli kansantaloudessa oli kenties yllättävää, erityisesti kun huomioidaan kuinka vähän toimiala on saanut huomiota osakseen taloushistorian tutkimuksessa. Tutkimus osoitti, että Suomen vienti oli pääomavaltaisempaa kuin tuonti. Vaikka tämän tuloksen tulkinta on varauksellinen, tutkimus pystyi osoittamaan ja kvantifioimaan toimialojen työ- ja pääomapanoksen osuuden tuotoksesta yksityiskohtaisesti. Panos-tuotosmallilla arvioitiin puuteollisuuden, paperiteollisuuden ja rakennustoiminnan ajanjaksona 1928-32 tapahtuneen loppukäytön muutoksen vaikutusta kansantalouteen. Merkittävä havainto on, että rakennustoiminnan loppukäytön muutoksella oli erittäin suuri kasvua vähentävä vaikutus koko kansantaloudessa. Talonrakennusinvestointien romahtaminen aiheutti lähes 13 prosentin tuotannon laskun kansantaloudessa. Vaikutus oli jopa suurempi kuin puuteollisuuden viennin romahtamisen. Tulokset osoittavat toisaalta, että yksityisen kulutuksen merkitys kansantaloudelle oli erittäin vahva. Esimerkiksi puuteollisuuden viennin romahtaminen aiheutti yli 4 % tuotannon vähenemisen mutta huomioitaessa mallissa myös yksityisen kulutuksen väheneminen, oli kokonaisvaikutus yli 10 %. Yksityisen kulutuksen huomioiminen mallissa siis yli kaksinkertaisti toimialojen vaikutukset kansantalouteen. Tulokset vahvistivat aiemmissa tutkimuksissa esitettyjä johtopäätöksiä tullipolitiikasta ja osoittivat maatalouteen läheisesti liittyvän elintarviketeollisuuden olleen eniten suojeltu toimiala kansantaloudessa. Muut kotimarkkinoiden toimialat eivät kuitenkaan hyötyneet tullipolitiikasta lamakauden aikana. Panos-tuotoshintamallilla osoitettiin, ettei tullipolitiikka ollut niin onnistunutta kuin aikalaistutkimuksissa väitettiin, vaan tullit korkeintaan pystyivät hidastamaan hintojen alenemista. Tutkimuksen liitteenä esitetään kaikki keskeiset Suomen kansantaloutta vuonna 1928 kuvaavat tilastolliset taulukot, mukaan lukien käyttö- ja tarjontataulukot, panos-tuotostaulukot, panoskertoimet, Leontiefin käänteismatriisi sekä työ- ja pääomapanoskertoimet.

Studies on Aerosol Particle Emission, Sampling and Authenticity

Emissions of coal combustion fly ash through real scale ElectroStatic Precipitators (ESP) were studied in different coal combustion and operation conditions. Sub-micron fly-ash aerosol emission from a power plant boiler and the ESP were determined and consequently the aerosol penetration, as based on electrical mobility measurements, thus giving thereby an indication for an estimate on the size and the maximum extent that the small particles can escape. The experimentals indicate a maximum penetration of 4% to 20 % of the small particles, as counted on number basis instead of the normally used mass basis, while simultaneously the ESP is operating at a nearly 100% collection efficiency on mass basis. Although the size range as such seems to appear independent of the coal, of the boiler or even of the device used for the emission control, the maximum penetration level on the number basis depends on the ESP operating parameters. The measured emissions were stable during stable boiler operation for a fired coal, and the emissions seemed each to be different indicating that the sub-micron size distribution of the fly-ash could be used as a specific characteristics for recognition, for instance for authenticity, provided with an indication of known stable operation. Consequently, the results on the emissions suggest an optimum particle size range for environmental monitoring in respect to the probability of finding traces from the samples. The current work embodies also an authentication system for aerosol samples for post-inspection from any macroscopic sample piece. The system can comprise newly introduced new devices, for mutually independent use, or, for use in a combination with each other, as arranged in order to promote the sampling operation length and/or the tag selection diversity. The tag for the samples can be based on naturally occurring measures and/or added measures of authenticity in a suitable combination. The method involves not only military related applications but those in civil industries as well. Alternatively to the samples, the system can be applied to ink for note printing or other monetary valued papers, but also in a filter manufacturing for marking fibrous filters.

Essays on Platforms: Business Strategies, Regulation and Policy in Telecommunications, Media and Technology Industries

The growth of the information economy has been stellar in the last decade. General-purpose technologies such as the computer and the Internet have promoted productivity growth in a large number of industries. The effect on telecommunications, media and technology industries has been particularly strong. These industries include mobile telecommunications, printing and publishing, broadcasting, software, hardware and Internet services. There have been large structural changes, which have led to new questions on business strategies, regulation and policy. This thesis focuses on four such questions and answers them by extending the theoretical literature on platforms. The questions (with short answers) are: (i) Do we need to regulate how Internet service providers discriminate between content providers? (Yes.) (ii) What are the welfare effects of allowing consumers to pay to remove advertisements from advertisement-supported products?(Ambiguous, but those watching ads are worse off.) (iii) Why are some markets characterized by open platforms, extendable by third parties, and some by closed platforms, which are not extendable? (It is a trade-off between intensified competition for consumers and benefits from third parties) (iv) Do private platform providers allow third parties to access their platform when it is socially desirable? (No.)

The Quest for Well-being in Growth Industries: Contexts, Research Design and Methodological Development

This Working Paper reports the background to the first stage of the ongoing research project, The Quest for Well-being in Growth Industries: A Collaborative Study in Finland and Scotland, conducted under the auspices of the Academy of Finland research programme The Future of Work and Well-being (2008-2011). This collaborative project provides national and transnational data, analysis and outputs. The study is being conducted in the Department of Management and Organisation, Hanken School of Economics, Finland, in collaboration with Glasgow Caledonian University, University of East London, Heriot-Watt University and Reading University, UK. The project examines policies and practices towards the enhancement of work-related well-being in growth industries, and contradictory pressures and tensions posed in this situation. The overall aim is to evaluate the development, implementation and use of work-related well-being policies in four selected growth industries. These sectors – electronics, care, finance and accounting, and tourism – have been selected on the basis of European Union and national forecasts, and demographic and socio-economic trends in employment. In this working paper we outline the background to the research study, the initial research plan, and how the survey of employers has been constructed. The working paper concludes with a brief discussion of general ongoing research issues arising in the project.

The Quest for Well-being in Growth Industries 2: The Survey

This working paper reports the ongoing research conducted in the research project, The Quest for Well-being in Growth Industries: A Collaborative Study in Finland and Scotland, under the auspices of Academy of Finland research programme, The Future of Work and Well-being. The research project examines the contradictory pressures for policies and practices towards both the inhibition and the enhancement of work-related well-being that are likely in growth industries. The overall aim is to evaluate the development, implementation and use of work-related well-being policies in four selected growth industries. These – electronics, care, finance and accounting, and tourism – have been selected on the basis of EU and national forecasts, and demographic and socio-economic trends in standard and non-standard employment. In this paper we aim to review the survey that constitutes the second main phase of this research.