Dissertations / Theses on the topic 'Pharmaceuticals'
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Walsh, William M. "Ethical pharmaceuticals? : a deeper look at the ethics in pharmaceutical public relations /." Full text available online, 2006. http://www.lib.rowan.edu/find/theses.
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Tibshraeny, Alexa Frances. "ENTREPRENEURIAL PROFILE: King Pharmaceuticals." Thesis, The University of Arizona, 2009. http://hdl.handle.net/10150/193004.
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Hernandez, Abdel. "Pharmaceuticals in Southern Arizona." Thesis, The University of Arizona, 2012. http://hdl.handle.net/10150/245084.
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The pharmaceutical industry is a potentially powerful but untapped industry in Southern Arizona. One such company in this industry is Topical Technologies, which develops topical solutions to treat skin cancer, and was founded by University of Arizona Cancer Center researchers. We conducted our primary research in the form of one-on-one interviews with diverse experts in a variety of fields; Dr. Robert Dorr, Co-Founder of Topical Technologies, Dr. Steve Stratton, Associate Professor of Medicine at AZCC, Robert Morrison, the Executive Director of the Desert Angels, Marie Wesselhoft, former Director of the Arizona Center for Innovation, and Dr. Debra Hanna, Associate Director of C-Path. We also conducted secondary research into the pharmaceutical industry. After conducting our research and analyzing the data, we formulated several recommendations to Tech Launch Arizona including: *Fostering relationships between the University leadership, business school, and BIO5 Institute *Forming long-term relationships with corporations *Building a venture portfolio that invests in multiple industries *Partnering with the Critical Path Institute We believe these recommendations will help create a more efficient environment for pharmaceutical companies to be successful.
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HU, MUYANG. "GLOBAL PHARMACEUTICAL OUTSOURCING STRATEGY REPORT FOR SMALL PHARMACEUTICAL COMPANIES." Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1463662432.
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Makowski, Marcin. "Solvent nanofiltration for purifying pharmaceuticals." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/29227.
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The projections recently published by the United Nations (UN) suggest that the global population may reach 8.9 billion people by the year 2050. Life expectancy is assumed to rise constantly with no upper limit and by the year 2100 is expected to vary from 66 to 97 years. As the population ages the demand for effective medicines is rising. At the same time the pharmaceutical industry keeps applying pressure to shorten development timelines for new chemical entities, so that new medicines can reach patients much faster. In the development and manufacturing of drugs the purification steps often consume the highest proportion of the processing time and costs. In parallel, there has been a surge in the expectations of patients regarding the purity of the desired pharmaceuticals. There are several processes available for yielding purified product: liquid chromatography, crystallization or distillation among others most of them, however have limitations. Therefore, progress is required in innovative technologies and processes characterized by higher stability, better selectivity and lower energy requirements. Applying membrane technology in the separation and purification of compounds can result in lower operating temperatures being needed, and less harsh conditions required, when compared to other processes. Thus it is of interest for Active Pharmaceutical Ingredient (API) manufacturing. Polymeric membranes are the most widely used for industrial membrane applications. However, an important challenge is to apply the existing polymeric membranes (suitable for aqueous operations) to non-aqueous solutions. Recent progress has led to the development of Organic Solvent Nanofiltration (OSN). OSN utilises solvent-resistant polymeric membranes to selectively retain solutes, and simultaneously allows smaller molecules to pass through the membrane. Nevertheless, ways in which membrane performance impacts the overall purification process have not yet been fully studied. Developing mathematical models of purification processes might help to better understand, and therefore better predict and control, the membrane process. Knowing the importance of a membrane in a filtration process, one should try to identify the areas where new membranes are desired. At the same time, one should try to understand how factors influencing membrane formation will affect membrane's final performance. As a benefit of the research conducted, by the end of this study the knowledge gained should result in the fabrication of membranes with enhanced capabilities.
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Gauthier, Herve. "Biodegradation of pharmaceuticals by microorganisms." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32347.
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The presence of pharmaceutical residues in water poses a serious treat to human health. The fate of many of these pharmaceuticals in the environment has not been thoroughly investigated. Sulfamethoxazole, sulfamethizole, trimethoprim and carbamazepine are among these pharmaceuticals with significant bioactivity that are considered to be persistent pollutants. The biodegradation of these compounds has been studied in this project in order to assess the fate of these pharmaceuticals in the environment. An easily degradable carbon source was added in these biodegradation experiments to optimize co-metabolism as a removal mechanism. Five microorganisms were used to determine if the selected drugs were biodegradable and, also, to identify the metabolites arising from their biodegradation. It was demonstrated that biodegradation occurred for sulfamethoxazole, sulfamethizole and carbamazepine. Trimethoprim showed a high resistance to biodegradation. It appeared that the microorganism Rhodococcus rhodochrous showed a particular ability to degrade the pharmaceuticals. The presence of metabolites was confirmed by HPLC and mass spectra analyses.La présence de résidus de produits pharmaceutiques dans l'eau représente une sérieuse menace pour l'environnement et la santé humaine. Le devenir de ces produits pharmaceutiques dans l'environnement n'a pas été adéquatement étudié. Le sulfaméthoxazole, le sulfaméthizole, le triméthoprime ainsi que le carbamazepine sont parmi ces composés pharmaceutiques qui ont une importante bioactivité et sont considérés comme polluants persistants. Dans ce projet, la biodégradation des ces produits à été étudiée afin d'évaluer le devenir de ceux-ci dans l'environnement. Une source de carbone facilement biodégradable a été utilisé lors des expériences afin de stimuler le mécanisme d`élimination par co-métabolisme. Cinq microorganismes ont été utilisés afin d'évaluer la biodégradabilité des produits pharmaceutiques sélectionnés et aussi identifier les métabolites résultant de leur biodégradation. Il a été démontré que la biodégradation est survenue pour le sulfaméthoxazole, le sulfaméthizole ainsi que le carbamazépine. Le triméthoprime à quant lui démontré une forte résistance à la biodégradation. Le microorganisme Rhodococcus rhodochrous a démontré une habileté particulière à dégrader les produits pharmaceutiques. La présence de métabolites a également été confirmée par analyse HPLC et spectrometrie de masse.
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CAPOZZI, LUIGI CARLO. "Continuous Freeze-Drying of Pharmaceuticals." Doctoral thesis, Politecnico di Torino, 2019. http://hdl.handle.net/11583/2749555.
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Du, Plooy Hilde. "Measuring brand loyalty in the pharmaceutical industry of South Africa / Hilde du Plooy." Thesis, North-West University, 2012. http://hdl.handle.net/10394/8685.
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Brands are recognised as one of the most valuable assets that a company can
possess and therefore brands are key role-players in the business strategies of
organisations. The rivalry amongst competitors in the pharmaceutical industry is
fierce and companies should design their strategies in such a way in order to
achieve competitive advantage. Brand loyalty is regarded as a powerful tool in the
development of pharmaceutical brands.
The main aim of this study was to measure brand loyalty in the pharmaceutical
industry of South Africa and to establish whether patients are brand loyal to original
pharmaceutical brands and the influence of generics on pharmaceutical brand
loyalty. The measurement of brand loyalty in the pharmaceutical industry is based on
Moolla’s brand loyalty framework for the FMCG (fast moving consumer goods)
industry. This study also aimed to determine whether Moolla’s FMCG brand loyalty
framework is applicable to the pharmaceutical industry. The twelve brand loyalty
influences identified by Moolla are: Customer satisfaction; Switching costs; Brand
trust; Repeat purchase; Involvement; Perceived value; Commitment; Relationship
proneness; Brand affect; Brand relevance; Brand performance and Culture.
The empirical study was conducted among 250 over-the-counter medicine
consumers with different demographic profiles. The methodology included the
sampling procedure, data collection, questionnaire development and statistical
techniques used. Results were analysed with regards to Factor analysis; the Kaiser-
Meyer-Olkin measure of sampling adequacy; Cronbach Alpha coefficients; Bartlett’s
test of sphericity, mean values and effect sizes. The Empirical results through
quantitative analysis included the validity of the research instruments, the calculation
of the reliability coefficients which reported on the significance of the research
variables. The results were presented in a conceptual framework to measure
pharmaceutical brand loyalty.
The results of this study concluded that the brand loyalty influences as identified by
Moolla are important for measuring pharmaceutical brand loyalty. The results of this
study also concluded that patients are indeed brand loyal and do prefer branded pharmaceuticals to generic pharmaceuticals in the over-the-counter medicine
industry of South Africa. The importance of this study is the contribution of a brand
loyalty framework to measure pharmaceutical brand loyalty which will aid
pharmaceutical companies in the strategic management thereof.Thesis (MBA)--North-West University, Potchefstroom Campus, 2013
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Cruz, Morató Carles. "Biodegradation of pharmaceuticals by Trametes versicolor." Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/283222.
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Els fàrmacs (PhACs) són un important grup de contaminants emergents que degut a la seva presència en el medi ambient i la seva difícil degradació han aixecat un gran interès en la comunitat científica. Alguns d’aquests PhACs són àmpliament utilitzats sense recepta i després de la seva ingestió son excretats per la orina i els fems, ja sigui en forma de compost actiu o com a metabòlit. Aquests productes entren a les estacions depuradores d’aigües residuals, on alguns d’aquests compostos no són eliminats eficaçment, sent capaços d’arribar a les aigües superficials, subterrànies i, posteriorment, a l’aigua potable.
El present treball avalua la viabilitat de la bioremeïació dels PhACs per fongs de podridura blanca. Aquests fongs tenen el potencial de degradar una àmplia gamma de contaminants xenobiòtics i recalcitrants degut al seu sistema enzimàtic inespecífic, capaç d’actuar sobre diversos substrats a través de l’acció d’enzims intracel·lulars (com el citocrom P450) i extracel·lulars (com la lacasa i peroxidasas). De tots els fongs, s’ha escollit Trametes versicolor per dur a terme l’estudi sobre la degradació d’analgèsics i anti-inflamatoris (ketoprofen i diclofenac), antiepilèptics (carbamazepina), reguladors de lípids (àcid clofibric), antibiotics (ofloxacina) i un agent de contrast per rajos X (iopromida).
El primer pas en la investigació va consistir en el estudi de la degradació de PhACs de forma individual per T. versicolor a escala Erlenmeyer i en condicions estèrils. Per tal d’obtenir més coneixements en el mecanisme de degradació dels PhACs pel fong, es va estudiar en detall la transformació dels fàrmacs anteriorment esmentats i en alguns casos es va proposar la via de degradació. Paral·lelament es va estudiar els enzims implicats en la degradació dels PhACs. També es va avaluar la toxicitat del brou de cultiu, on els productes de degradació estaven presents i d’aquesta manera poder observar si els compostos produïts son més tòxics que el propi fàrmac.
Posteriorment, amb l’objectiu d’escalar el procés de la degradació de PhACs, es va utilitzar un bioreactor de llit fluïditzat per la eliminació de la carbamazepina i de l’àcid clofibric, operat tant en continu com discontinu. En els resultats també es va incloure la identificació dels productes de transformació, junt amb l’avaluació de la toxicitat dels efluents.
D’altra banda, a causa del gran nombre de publicacions sobre la degradació de PhACs individuals per fongs publicats durant el transcurs d’aquesta tesis, es va realitzar una revisió bibliogràfica sobre aquest camp de recerca.
Per últim, en un intent d’escalar el procés a nivells més reals i per tant proporcionar una millor estimació del possible impacte ambiental de l’aplicació d’aquest procés, es va tractar una aigua residual urbana i d’hospital en un bioreactor operat en discontinu. El tractament de l’aigua residual es va fer en condicions no estèrils, on altres microorganismes estan presents, i a les concentracions preexistents dels contaminants, és a dir, sense afegir cap contaminant. En un experiment preliminar amb l’aigua residual urbana, es va observar la necessitat d’afegir una font addicional de carboni i nitrogen per mantenir l’activitat del fong. Per altra banda, els resultats obtinguts van ser positius ja que es va observar l’eliminació de gairebé tots els PhACs detectats en les aigües urbanes i d’hospital, juntament amb una notable reducció de la toxicitat global després del tractament, el que fa concloure que pot ser un tractament adequat i cal seguir investigant en altres aspectes per desenvolupar i optimitzar el procés abans de implementar-lo a escala real.Pharmaceutical active compounds (PhACs) are an important group of emerging contaminants that have raised an increasing interest in the scientific community due to their ubiquitous presence in the environment and their difficult degradation. Some of these drugs are extensively used as non-prescription drugs and after their intake, are excreted with urine and faeces either as active substances or metabolites. These substances come into wastewater treatment plants where some compounds are not efficiently removed, being able to reach surface, groundwater and subsequently, drinking water. The present work assesses the feasibility of PhACs bioremediation by white-rot fungi (WRF). WRF have the potential to degrade a wide range of xenobiotic and recalcitrant contaminants due to their unspecific enzymatic system, able to act on diverse substrates through the action of intracellular (i.e. cytrochrome P450 system) and extracellular (i.e laccases and peroxidases) enzymes. The fungus Trametes versicolor has been chosen to carry out the degradation study of some analgesics and anti-inflammatory (ketoprofen and diclofenac), anti-epileptics (carbamazepine), lipid regulators (clofibric acid), antibiotics (ofloxacin) and a X-ray contrast agent (iopramide). The first step in the research deals with the preliminary assessment of the individual PhACs degradation by T. versicolor at Erlenmeyer scale and sterile conditions. To obtain further insights in the mechanism of PhACs degradation by the fungus, the transformation products were identified as well as the enzyme responsible for the degradation of the parent compound with the aim of proposing a degradation pathway. In addition, an assessment of the toxicity of the broth, where transformation products were present, was included. Furthermore, with the aim of scale up the PhACs degradation process, a fluidized bed bioreactor was employed for the degradation of carbamazepine and clofibric acid, operated in both continuous and batch mode. Results also include the identification of transformation products and the toxicity assessment.On the other hand, due to the great number of publications about the degradation of pharmaceuticals by white-rot fungi that appeared over the course of this thesis, it was decided to include a literature review to evaluate the current state of the art in this topic. Finally, in an attempt to scale up the process to real approaches and thus provide a better estimation of the potential environmental impact of the application of such process, T. versicolor was used in a non-sterile batch bioreactor treatment for the removal of pre-existent PhACs from urban and hospital wastewater, where many contaminants and other microorganism are present. In preliminary experiments with urban wastewater, it was found the necessity of an extra source of carbon and nitrogen to maintain the activity of the fungus in the wastewater. Moreover, an important removal was observed for almost all drugs detected in both urban and hospital wastewater, together with a remarkable reduction of the overall toxicity.
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Supriyanto, Ganden. "Chromatomembrane method applied in pharmaceuticals analysis." [S.l.] : [s.n.], 2005. http://www.diss.fu-berlin.de/2005/22/index.html.
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Franks, Carmen G., and University of Lethbridge Faculty of Arts and Science. "Phytoremediation of pharmaceuticals with salix exigua." Thesis, Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 2006, 2006. http://hdl.handle.net/10133/536.
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Municipal treated wastewater entering rivers contain biologically active pharmaceuticals capable of inducing effects in aquatic life. Phytoremediation of three of these pharmaceuticals and an herbicide was investigated using Sandbar willow (Salix exigua) and Arabidopsis thaliana. Both plants were effective at removing compounds from solution, with removal of 86% of the synthetic estrogen, 17α-ethynylestradiol, 65% of the anti-hypertensive, diltiazem, 60% of the anti-convulsant, diazepam (Valium®), and 51% of the herbicide atrazine, in 24 hours. Distribution of compounds within roots and shoots, in soluble and bound forms, differed among compounds. Uptake and distribution of pharmaceuticals within the study plants confirmed pharmaceutical behaviour can be predicted based on a physiochemical property, their octanol-water partitioning coefficients.
An effective method for detection of 17α-ethynylestradiol within surface water using solid phase extraction and gas chromatography-mass spectrometry was developed. Previously unreported breakdown of 17α-ethynylestradiol into another common estrogen, estrone, during preparative steps and gas chromatography was resolved.xv, 216 leaves ; 29 cm.
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Alem, Naziha. "Stability of amorphous pharmaceuticals : Calorimetric studies." Thesis, University of London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.529258.
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Ghislandi, Simone. "Essays in the economics of pharmaceuticals." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491394.
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The purpose of this thesis is to analyse how regulatory interventions in the market for pharmaceuticals can affect agents' decisions and market outcomes. The work is organized in four main chapters. The first chapter is theoretical and analyses firms' dynamic pricing under a Reference Pricing Scheme. In a new theoretical setting, we explore whether and why competition among firms' works, pointing out the role of the scheme in facilitating any collusive behavior.
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Gillott, Nicola C. "Capillary electrochromatography : retention behaviour of pharmaceuticals." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312243.
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Thorley, Fiona Carolynne. "Analysis of pharmaceuticals by Raman microscopy." Thesis, University of Leeds, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.400848.
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Carter, Laura. "Uptake of pharmaceuticals into terrestrial organisms." Thesis, University of York, 2013. http://etheses.whiterose.ac.uk/4678/.
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Over the past decade, there has been increasing scientific interest in the occurrence, fate and effects of pharmaceuticals in the environment. To date, the majority of this research has focussed on the aquatic environment whilst the terrestrial environment has remained relatively unexplored. Research carried out in the terrestrial environment has primarily focussed on the fate of pharmaceuticals in soils as well as the uptake of pharmaceuticals into plants. Less information is available on the uptake of pharmaceuticals into other soil dwelling species. The studies presented in the thesis were therefore performed to investigate the uptake of pharmaceuticals into earthworm species (Eisenia fetida and Lumbricus terrestris) and plant species (radish and ryegrass). Experiments were designed to explore the effect of pharmaceutical physico-chemical properties, soil parameters and species traits on the uptake of pharmaceuticals from soils into terrestrial species. Understanding the factors and processes involved in the uptake of these compounds from soils, is vital to adequately assess the risks of pharmaceuticals in the environment. Initial experimental studies evaluated the uptake of four pharmaceuticals, namely carbamazepine, diclofenac, fluoxetine and orlistat into the earthworm, Eisenia fetida. Pore water based bioconcentration factors (BCFs) increased in the order of carbamazepine < diclofenac < fluoxetine and orlistat. As well as experimental research, a desk based investigation was perfomed to assess the applicability of a minimised design approach to estimate bioconcentration factors (BCFs) in terrestrial and aquatic species. A significant regression between BCFminimised and BCFtraditional was found and this approach was therefore adopted to calculate earthworm BCFs in the soil parameters and species traits studies described below. The uptake of the four study pharmaceuticals by E. fetida was therefore further evaluated in different soil types. The uptake and accumulation of pharmaceuticals into E. fetida changed depending on soil type. Orlistat exhibited the highest pore water based bioconcentration factors (BCFs) and displayed the largest differences in uptake between soil types as BCFs ranged between 30.51 – 115.92. For carbamazepine, diclofenac and fluoxetine BCFs ranged between 1.05 – 1.61, 7.02 – 69.57 and 16.78 – 20.42 respectively. Supplementary studies compared the uptake of the study pharmaceuticals in two earthworms (Lumbricus terrestris and E. fetida). All four pharmaceuticals were taken up by both L. terrestris and E. fetida tissue after 21 d exposure to spiked soil. Pore water based bioconcentration factors (BCFs) ranged between 6.69 and 83.79 for L. terrestris and 1.14 and 63.03 for E. fetida. The effect of species type on the uptake of pharmaceuticals (carbamazepine, diclofenac, fluoxetine, propranolol, sulfamethazine) and a personal care product (triclosan) was also investigated in plant species (radish, Raphanus sativus and ryegrass, Lolium perenne). Five of the six chemicals were taken up into plant tissue, carbamazepine to the greatest extent in both the radish (52 µg/g) and ryegrass (33 µg/g) whereas sulfamethazine uptake was below the limit of quantitation (LOQ). The results demonstrate the ability of plant species and earthworms to accumulate pharmaceuticals from soils with uptake apparently specific to both species, chemical and soil type. However the influence of these individual parameters does not affect BCFs to a significant amount. The research also highlights that a combination of factors and processes appear to be driving the uptake into soil dwelling species as further analysis was unable to find a single parameter to adequately explain pharmaceutical uptake into terrestrial species. For example, for plant uptake, results could only be partly explained by the hydrophobicity and extent of ionisation of each chemical in the soil. Even though these chemicals are taken up by earthworms and plants, further analysis showed that the risk to predatory birds is minimal based on the current environmental scenarios as thousands of worms would have to be consumed by a bird to receive a single dose. Similarly, the potential risk to humans consuming crops contaminated with pharmaceutical residues is also minimal. However with increasing loadings of pharmaceuticals to soils this may result in potential problems for human health and predatory birds in the future.
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Yoshioka-Tarver, Megumi. "Benzotriazole intermediates for heterocycles and pharmaceuticals." [Gainesville, Fla.] : University of Florida, 2009. http://purl.fcla.edu/fcla/etd/UFE0041025.
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Guo, Jiahua. "Impact of pharmaceuticals on algal species." Thesis, University of York, 2015. http://etheses.whiterose.ac.uk/12390/.
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Trace amounts of activated pharmaceutical ingredients (APIs) have been reported in aquatic environments worldwide, and their toxicity to non-target organisms is of increasing concern. Algae are primary producers in aquatic food chains, and as such are very sensitive to external disturbance. The understanding of the adverse effects on the algal species such as growth and physiological effects is vital to understand the risks of APIs in the aquatic environment. This thesis therefore describes desk-based studies and a series of laboratory experiments to characterise the risk of APIs, and to investigate the effects of APIs on a wide range of algal species. In the desk-study, a review summarising the available ecotoxicological data of APIs to algal species was initially performed, where differences in the sensitivity of the algal species towards API exposures were found. After that, an approach for prioritising APIs and associated metabolites in the UK environment was developed, where three major-use antibiotics lincomycin, tylosin and trimethoprim that pose a potential threat to algal species in the natural environment were identified for further experimental investigation. Laboratory experiments were then conducted to investigate the effects of three antibiotics on the growth and physiology of a range of algal species from chlorophytes, cyanobacteria and diatoms. Risk arising from the antibiotic mixture in the European surface waters was characterised In conclusion three major-use antibiotics could cause inhibitory effects on both algal growth and physiology. At environmentally relevant concentrations the antibiotic mixtures can pose potential risks in European surface waters.
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McLay, Paula. "Iron binding by certain anticancer pharmaceuticals." Thesis, McLay, Paula (1992) Iron binding by certain anticancer pharmaceuticals. PhD thesis, Murdoch University, 1992. https://researchrepository.murdoch.edu.au/id/eprint/52205/.
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The importance of Fe(III)-chelation in the biological activity of the anticancer pharmaceutical Razoxane has been investigated. Since Razoxane is known to be hydrolysed in vivo to form a potential complexing agent, the observed biological effect o(Razoxane (ICRF 159) and two less active homologues (ICRF 154 and ICRF 192) were compared with the properties of their hydrolysis products; ICRF 198 (N ,N'-dicarboxamidomethy 1-N ,N'-dicarboxymethyl-1,2-diaminopropane, ICRF 175 (N,N'-dicarboxamidomethyl-N,N'-dicarboxymethyl-1,2-diamino-ethane) and ICRF 226 (N,N'-dicarboxarnidomethyl-N,N'-dicarboxymethyl-1,2-diaminobutane), respectively. The equilibrium constants for the binding of these compounds with Fe(III) were determined by cyclic voltammetry and potentiometric titration. In addition, equilibrium constants of ICRF 175 and 198 binding with Zn(II) and of citrate binding with Fe(III) were determined. Relevant equilibrium constants for the binding of the proton with these complexing agents were also obtained. These constants were incorporated into a computer simulation model of blood plasma, permitting calculation of the extent of chelation of these agents in vivo. Differences were observed in the ability of the compounds to complex Fe(III) under physiological conditions. Nevertheless, it was concluded that the anticancer activity of Razoxane is not directly related to Fe(III) chelation.
The rates of reaction of superoxide (O-2) with the Zn(II), Cu(II) and Fe(III) complexes of EDTA, DTPA, ICRF 175, I 98 and 226 were subsequently measured by pulse radiolysis. Significantly, ICRF 198-Fe(III) was found to react relatively rapidly with superoxide. In addition, the computer simulations indicate that the presence of ICRF 198 would restrict the formation of iron complexes of the anticancer pharmaceutical Adriamycin, these complexes being implicated in its cardiotoxicity. The ability to compete in vivo for iron and to react with superoxide thus appear to be important aspects of the mechanism of action of Razoxane to protect against the clinically-important side-effects of Adriamycin administration.
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Stros, Michael. "The influence of marketing factors and substance characteristics on pharmaceutical sales in a state-controlled prescriptions pharmaceuticals market." Thesis, Aston University, 2012. http://publications.aston.ac.uk/18724/.
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The present dissertation investigates the influence of brand as well as substance-related marketing attributes on prescription pharmaceutical sales within a state-controlled market. For this purpose, a systematic literature review was conducted in the first instance, during which knowledge about the most relevant research within this field was gathered. Consequently, over 538 publications were reviewed and indicated as being potentially relevant, leading to an eventual count of 98 core publications. However, most of these studies had been conducted in the mainly unrestricted US market. These findings were then summarised and statistically evaluated. In a second step, based on the literature review, a qualitative study, containing focus and Delphi groups, was then performed. The participants in these studies were involved in pharmaceutical marketing within a state-controlled prescriptions pharmaceuticals market. Consequently, the findings were slightly different to those derived by the systematic literature review. Based on this second step, seven hypotheses were proposed. In the third step, these hypotheses were tested, using collected data and a secondary market dataset provided by a market research institute. A statistical analysis was then performed, applying descriptive as well as multiple regression analytical methods. The evaluation of the results resulted in a conceptual model of physician targeting, leading to several theoretical, methodological and managerial implications.
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Karaca, Zeynal. "Essays on pharmaceuticals and health care expenditures." Thesis, [College Station, Tex. : Texas A&M University, 2007. http://hdl.handle.net/1969.1/ETD-TAMU-1915.
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Brits, Marius. "Solid-state properties of pharmaceuticals / Marius Brits." Thesis, North-West University, 2008. http://hdl.handle.net/10394/2023.
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Bis, Joanna A. "Crystal engineering of organic compounds including pharmaceuticals." [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001424.
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Hussain, Syed. "Removal of poultry pharmaceuticals by constructed wetlands." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104564.
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The main focus of the study was on three ionophoric antibiotics, monensin salinomycin and narasin. These three pharmaceuticals were evaluated both in vivo and in vitro setups to understand their fate and behavior in a constructed wetland (CW) environment. The laboratory studies determined the sorption, degradation and photodegradation potential in context of a wetland setup and, the field-scale CW experiments appraised the pharmaceutical removal potential under three flow configurations: free water surface (FWS), horizontal subsurface flow (HSSF) and vertical flow (VF) systems. FWS and HSSF systems were evaluated with two texturally different soils while the vertical system employed sphagnum peat moss. The laboratory sorption study was conducted on both soils at three pH levels, namely 4.5, 6.8, and 8.5. At pH 6.8, it was found that the sandy clay loam soil had higher Kd values for all three antibiotics as compared to the sandy soil. Narasin showed the highest Kd and Koc, whereas the lowest were observed for monensin. The sorption of all compounds had an inverse relationship with pH. In the biodegradation study on both soils, three concentrations of each compound, 100, 500, and 1000 μg kg-1, were used. First order degradation was observed for all three pharmaceuticals, with half-lives ranging from 6 to 8 days in both soils. The photodegradation study was carried out at three concentrations of each pharmaceutical on sterilized milli-Q water, sterilized milli-Q water with nitrate-N, and sterilized wetland water. Photodegradation was observed only for the wetland water; it also followed first-order decay with a half-life of 55, 40, and 37 days for monensin, salinomycin, and narasin, respectively. The first CW study determined the removal efficiency of two FWS wetland systems, one with sandy clay loam soil and the other with sandy soil, and a VF system with sphagnum peat moss for monensin, salinomycin and narasin. The results showed a significantly higher removal (P< 0.01) of all three antibiotics in FWS system using the sandy soil as compared to the CW on the sandy clay loam soil substrate. The ability to infiltrate to greater depths of the soil profile is likely to provide greater opportunity for soil-to-solute interactions, resulting in higher attenuation mainly through sorption in the sandy soil. However compared to the FWS systems, significantly enhanced removal (P < 0.0001) was observed in VF system using peat. Monensin and narasin were found to be the most and the least mobile in all three systems. The second field study assessed the removal potential of the sandy soil in a field scale horizontal subsurface flow (HSSF) treatment wetland for the three antibiotics. Compared to the FWS treatment, the HSSF treatment significantly (P < 0.001) removed greater monensin (40% vs 32%), salinomycin (49% vs 34%) and narasin (49% vs 38%). Based on temperature, oxidation-reduction potential and dissolved oxygen measurements, significant contribution of microbial degradation could not be confirmed.In another study, N-removing bacterial strains were isolated from an antibiotic exposed wetland. The strains were identified using nucleotide sequence analysis of the 16S rRNA gene; the isolates were assessed for their ability to withstand these pharmaceuticals. A Bacillus subtilis strain BRAZ2B was found to thrive in the drug-exposed wetland environment.Des méthodes à la fois in vivo et in vitro servirent à élucider le devenir et le comportement de trois antibiotiques ionophores (monensin, salinomycine and narasine) dans l'environnement d'un marais artificiel (MA). Des études in vitro en laboratoire établirent le potentiel de sorption et de décomposition de ces composés dans un loam sablo-argileux et un sol sableux, ainsi que celui de photodégradation dans l'eau de marécage. Des études avec MA à l'échelle préindustrielle déterminèrent le potential d'élimination de ces trois produits pharmaceutiques sous trois types d'écoulement: en surface libre (FWS), souterrain horizontal (HSSF) et en circulation verticale (VF). Le système FWS fut évalué avec les deux types de sols, tandis que le système HSSF ne fut évalué que pour le sol sablonneux. Le système de circulation en vertical utilisa de la tourbe mousseuse de sphaignes. In vitro le niveau de sorption des composés présenta une relation inverse au pH pour des valeurs de 4.5, 6.8, and 8.5. À un pH de 6.8, les valeurs de Kd pour tous les composés furent plus élevés pour le loam sablo-argileux que pour le sol sableux. La narasine montra les valeurs les plus élevées de Kd and Koc, tandis que le monensin montra les moins élevées. Trois concentrations (100, 500, et 1000 μg kg-1) de chaque composé, appliqués sur chacun des deux sols, présentèrent tous une cinétique de dégradation de premier ordre, avec des demi-vie d'élimination de 6 à 8 jours. Le potential de photodégradation des trois composés fut évalué dans de l'eau de marécage pré-stérilisé, de l'eau distillé (milli-Q) et de l'eau distillé dopé de nitrates. La photodégradation n'eut lieu que dans l'eau de marécage, où elle suivit une cinétique de dégradation de premier ordre, avec des demi-vies d'élimination de 55, 40, et 37 jours, respectivement, pour le monensin, la salinomycine, and la narasine. Dans une première étude, on évalua l'éfficacité d'élimination de ces composés par les deux systèmes FWS — un avec loam sablo-argileux et un avec sol sableux — et un système VF avec tourbe mousseuse de sphaignes. Le système FWS avec sol sableux comme substrat élimina significativement plus les trois antibiotiques (P< 0.01) que celui avec un loam sablo-argileux. La capacité des composés dissouts de pénétrer le profil sableux permit probablement des conditions plus favorables aux interactions sol-soluté. Ceci aurait ensuite permis une plus ample atténuation, principalement par sorption au sol sablonneux. Le rôle de la biodégradation, particulièrement dans le loam sablo-argileux, fut aussi noté. Cependant, comparé aux systèmes FWS, le système VF avec tourbe permit une élimination significativement plus élevée (P < 0.0001). Dans les trois systèmes, le monensin et la narasine s'avérèrent les composés le plus et le moins mobile, respectivement. Dans une seconde étude on évalua le potentiel d'élimination des trois antibiotiques grâce à un système HSSF pleine échelle avec sol sablonneux. Comparé au système FWS comportant le même substrat, le système HSSF élimina significativement (P < 0.01) plus de monensin (40% vs. 32%), salinomycine (49% vs. 34%) et narasine (49% vs. 38%). Un suivi de la température, du potentiel d'oxydo-réduction et de l'oxygène dissout, ne permirent pas de confirmer une contribution significative de la dégradation microbienne.En une dernière étude, des souches bactériennes compétentes à l'élimination de l'azote furent isolées d'un marécage exposé à des antibiotiques. Ces souches furent identifiées par détermination de la séquence nucléotidique d'ARNr 16s, et leur capacité de résister à ces composés pharmaceutiques fut évaluée. Une souche de Bacillus subtilis (BRAZ2B) s'avéra capable de se développer vigoureusement dans l'environnement du marécage exposé à ces composés.
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Huang, Xingye. "Chiral separation of pharmaceuticals by capillary electrophoresis." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/11645/.
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Conventional capillary zone electrophoresis (CZE) methods, with simple buffer solute, natural or derivatized cyclodextrin and organic additive in BGE, have been developed for a group of ten standard chiral pharmaceutical compounds representing different physiochemical properties and pharmaceutical activities. In this study, factors affecting chiral separation in CZE, including BGE pH value, ionic strength, chiral selector type, selector concentration and organic additives, were optimized. A maximum of eight standard compounds were separated by three different standard methods which were developed. The electrophoretic behaviours of the standard compounds observed were in good agreement with the literature. Partial filling technique (PFT) was studied as a complementary approach to conventional CZE methods for enantioseparation of standard compounds. Partial filling time, selector type and concentration were investigated; a maximum of seven standard compounds were separated by optimized filling time and three different chiral selectors. However, for five of the separated pharmaceuticals, the chiral resolutions achieved were much lower than those obtained from conventional CZE methods. Key observations from the experiment were supported by previous research. For the first time, glycidol was evaluated as a covalently bonded coating material on CE capillary for enantioseparation. Hyperbranched polyglycidol brushes were grown directly from Si/SiO2 surface via anionic ring-opening polymerization, using surface Si-OH groups as initiator. This grafting-form technique eliminated the need for initiator functionalized self-assembled monolayers on the surface, and the thickness and complexity of the hyperbranched polymer brushes could be well controlled in this process. Polyglycidol coating was established on the surface of glass slides and then adapted to CE capillary. Both fused silica capillary and etched capillary were used to examine the electrophoretic properties of polyglycidol coating. Chiral polyglycidol coating was compared with the standard CZE method developed and showed excellent chiral selectivity for standard compounds. Nine out of ten standard compounds were separated with poly-S-glycidol coated capillary, using simple buffer solute containing organic additive. Application of etched capillary further improved the enantioseparation resolution and peak efficiency for those standard compounds. Stability and coating regeneration ability were studied. Polyglycidol coating developed on CE capillary gradually lost its chiral selectivity after 50 30-min runs with acidic BGE. Coating regeneration on the remaining surface was difficult. The result indicated that glycidol isomer can be used as monomer for in situ polymerization in CE capillaries and the coating formed on the inner surface has potential chiral selectivity toward various pharmaceuticals, which is equal or better than traditional chiral CE.
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Skaria, Cyrus Victor. "Stability assessment of pharmaceuticals using isothermal calorimetry." Thesis, University College London (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582544.
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Pharmaceuticals are formulated to be stable products and hence studying their stability using conventional techniques can be difficult and time consuming. Isothermal calorimetry has the potential to study stability of pharmaceuticals, as it is sensitive enough to detect extremely small heat flows associated with change (chemical or physical). Its use in the pharmaceutical arena has not been widespread because of the difficulties associated with analysing data recorded from complex processes, since heat is ubiquitous. The work presented in this thesis demonstrates the applicability of isothermal calorimetry in the stability assessment of pharmaceutical model systems. Calorimetric data recorded for complex processes were analysed based on kinetic modelling. Initial studies involved the degradation of simple single-step processes '(hydrolysis of aspirin), followed by model systems with increasing complexity. Degradation involving parallel processes - binary mixtures of para bens was studied. Using kinetic models, rate constants and reaction enthalpies were determined for individual processes. Data recorded for consecutive reactions, commonly encountered in pharmaceuticals can be difficult to analyse if exact mechanisms are unknown. The use of chemometric techniques to analyse calorimetric data recorded for complex processes offers great potential when reaction mechanisms are unknown. The two-step consecutive reaction of potassium hydroxylamine disulfonate was successfully analysed for reaction parameters using kinetic-based models and chemometric analysis. ' Significant proportions of degradation in pharmaceuticals proceed at a slow rate and can pose difficulty in their assessment. Minimum desirable reaction parameters required to successfully analyse calorimetric data for slow reactions were generated and its use in designing calorimetric experiments were demonstrated. Finally the use of IC in the preformulation stages of drug development are emphasised, particularly its role in purity determination of impure aspirin and drug excipient compatibility. Compatibility between aspirin and magnesium stearate was investigated using IC and reaction parameters obtained were compared to those obtained using conventional chromatographic techniques.
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Paus, Raphael [Verfasser]. "Solubility and Dissolution of Pharmaceuticals / Raphael Paus." München : Verlag Dr. Hut, 2016. http://d-nb.info/1097817733/34.
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Barrett, L. J. "Raman spectroscopy of illicit drugs and pharmaceuticals." Thesis, Queen's University Belfast, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269165.
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Chu, Jhih-Wei 1973. "Oxidation of methionine residues in protein pharmaceuticals." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/28660.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004.Includes bibliographical references (p. 171-189).
(cont.) of free methionine. Therefore, the environments surrounding different methionine sites in G-CSF mainly provide spatial restriction to the access to the solvent but do not affect oxidation in a specific manner, consistent with the good correlation between 2SWCN's and the rates of oxidation. A comprehensive picture of oxidation is thus developed. It allows an accurate prediction of protein oxidation, and provides a rationale for developing strategies to control oxidation, such as modulating protein conformation via adding excipients. This knowledge could aid in developing in a more rational manner solvent formulations that protect therapeutic proteins against oxidation.
Oxidation of the amino acid methionine by peroxides in aqueous formulations of proteins is a critical issue in the development of therapeutic products. It must be controlled so that therapeutic proteins can maintain their activity. In addition, oxidized therapeutics are undesirable due to their possible immunogenetic effects. An understanding of the mechanism and the factors that influence the reactivity of different methionine sites toward oxidation is therefore important. In this thesis, computational methods are applied and developed to address these problems. First, a mechanism by which peroxides oxidize the sulfur atom of methionine is developed. The rate-limiting step was found to be the breaking of the O-O bond of H₂O₂ and the formation of the S-O bond during which significant charge separation is developed. The charge separation can be stabilized via specific interactions such as hydrogen bonding with surrounding water molecules. This "water-mediated" mechanism of oxidation is consistent with experimental data such as those on activation energies of oxidation and pH dependence of the rates of oxidation. Based on the "water-mediated" mechanism, a structural property, average 2-shell water coordination number (2SWCN), has been shown to correlate well to the rates of oxidation of different methionine groups in Granulocyte Colony-Stimulating Factor (G-CSF) and in a Human Parathyroid hormone fragment (hPTH(1-34)). Including the dynamics of protein and water molecules in an explicit manner was found to be important for such correlation. Via combined quantum mechanical and molecular mechanical free energy simulations, the activation free energies of the oxidation of methionine residues in G-CSF are found to be equivalent to the values for the oxidation
by Jhih-Wei Chu.
Ph.D.
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Johnston, Andrew James. "The atomic structure of pharmaceuticals in solution." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:817233d5-ea3a-4689-84a2-1de2c90f4f13.
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Investigations of the structure of indole, cocaine hydrochloride, alprazolam and clonidine hydrochloride in solution were undertaken using a combination of experimental, principally neutron di?raction, and computational techniques. This thesis aims to probe the interactions of the hydrophilic and hydrophobic groups of each these molecules with their solvent environment, drawing conclusions about how their interaction with solvent molecules and their conformation in solution are related to their biological function. Cocaine, alprazolam and clonidine are of particular interest because of their ability to cross the blood-brain barrier. Investigation of the solvation of indole, the functional group of the amino acid tryptophan, in methanol/water solutions highlighted the role played by electrostatic interactions between the benzene ring of indole and its environment in dictating the location of tryptophan in the membrane bilayer. By studying the hydration of cocaine in aqueous solution, a possible mechanism explaining the ability of cocaine to cross the blood-brain barrier in its protonated form, which involves shielding of its hydrophilic groups through a water mediated internal hydrogen bond, was proposed. The preferentially solvated regions of the benzodiazepine alprazolam in methanol/water solutions indicated that these regions coincide with the location of bridging water molecules in the crystal structure of alprazolam bound to the BRD4 protein, which regulates transcription of oncogenes. A similar analysis of the solvation of clonidine in methanol/water solutions supported hypotheses relating to the mechanism of action of clonidine occurring via binding to adrenoceptors rather than imidazoline receptors. The work presented in this thesis demonstrates the importance of determining the structure of biomolecules in solution in gaining a comprehensive understanding of their behaviour in vivo.
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Samoilenko, N., I. Yermakovych, and L. Mårtensson. "Water contamination of urban areas by pharmaceuticals." Thesis, Белорусский государственный технологический университет; Vilnius Gediminas Technical University, 2014. http://repository.kpi.kharkov.ua/handle/KhPI-Press/25401.
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The occurrence and fate data of pharmaceuticals in the environment were described in the article. The main list of pharmaceuticals groups identified in surface and sewage waters was shown according to studies of laboratories in the U.S. and Europe. The main approaches for reduction of pharmaceuticals releasing into environment and monitoring of surface water were considered.
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Calisto, Vânia Maria Amaro. "Environmental occurrence and fate of psychiatric pharmaceuticals." Doctoral thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/7026.
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Doutoramento em QuímicaOs fármacos são importantes contaminantes ambientais. Nas últimas duas décadas, o número de estudos sobre a ocorrência destes poluentes emergentes em matrizes ambientais aumentou significativamente. Esta ocorrência generalizada preocupa a comunidade científica devido a evidências que comprovam a sua capacidade de interferir nos ecossistemas, mesmo em concentrações muito baixas. No caso particular dos fármacos psiquiátricos é expectável que constituam um risco ecológico significativo. Para uma melhor compreensão do impacto real destes poluentes é essencial que se proceda a uma avaliação extensiva da sua persistência e destino em matrizes ambientais. Os estudos apresentados nesta tese pretendem contribuir para melhorar o conhecimento acerca da ocorrência, persistência e destino ambiental de fármacos psiquiátricos. Para este efeito, foram seleccionados, como objecto de estudo, dois grupos de fármacos: anti-epilépticos (carbamazepina) e fármacos com efeitos ansiolíticos e sedativos (as benzodiazepinas diazepam, oxazepam, lorazepam e alprazolam). A fotodegradação é o principal processo que afecta a persistência de poluentes orgânicos em ambientes aquáticos. Consequentemente, a persistência dos cinco fármacos seleccionados foi avaliada através de estudos de fotodegradação directa e indirecta, tendo em consideração a influência de parâmetros relevantes tais como pH, nível de oxigenação e matéria orgânica dissolvida. Os estudos de fotodegradação aqui descritos foram seguidos por cromatografia micelar electrocinética com a aplicação de um capilar com revestimento dinâmico. Adicionalmente, os fotoprodutos resultantes de fotodegradação directa foram identificados por espectrometria de massa. O estudo da carbamazepina no ambiente é particularmente relevante uma vez que esta foi proposta como um potencial marcador de poluição antropogénica. A sua ocorrência em água superficiais, de sub-solo e residuais foi investigada através da implementação de um ensaio imunológico (ELISA), optimizado para a aplicação a triagens ambientais e amostras com matrizes complexas. O destino deste fármaco na interface água/solo foi também investigado usando solos agrícolas submetidos a fertilizações de longo prazo; este estudo permitiu tirar conclusões acerca da contaminação de águas adjacentes por solos contaminados. O trabalho aqui descrito constitui uma abordagem multidisplinar à problemática da ocorrência de fármacos psiquiátricos no ambiente, contribuindo de forma relevante para esta área de estudo.
Pharmaceuticals are considered to be important environmental contaminants. During the last two decades, the number of studies reporting the occurrence of these emerging contaminants in a large variety of environmental matrices has undergone a dramatic increase. This widespread occurrence is raising awareness amongst the scientific community due to some evidence indicating their ability to interfere with ecosystems at extremely low concentrations. Psychiatric pharmaceuticals, in particular, are thought to impose significant ecological risks. A better understanding of the real impact of these pollutants implies a comprehensive evaluation of their persistence and fate in environmental matrices. The studies presented in this thesis aim at providing a significant contribution to increase the existing knowledge related to the occurrence, persistence and environmental fate of psychiatric pharmaceuticals. For this purpose, two groups of psychiatric pharmaceuticals were selected as object of study: anti-epileptics (carbamazepine) and pharmaceuticals with anxiolytic and sedative effects (the benzodiazepines diazepam, oxazepam, lorazepam and alprazolam). Photodegradation is considered to be the main process affecting the persistence of organic pollutants in aquatic environments. Consequently, the persistence of the five selected psychiatric pharmaceuticals was evaluated by performing direct and indirect photodegradation studies and considering the influence of some relevant parameters such as pH, oxygenation level and dissolved organic matter. The photodegradation studies hereby reported were followed by a newly developed micellar electrokinetic chromatography method, using a dynamically coated capillary. In addition, the photoproducts generated under direct photodegradation were identified by mass spectrometry. The study of carbamazepine in the environment is particularly relevant as this compound has been recently proposed as a possible marker of anthropogenic pollution. The occurrence of carbamazepine in surface, ground and wastewaters was investigated through the implementation of an immunoassay (ELISA), optimized to perform high throughput environmental screenings in complex matrices. Moreover, the fate of this pharmaceutical at the water/soil interface was studied using agricultural soils submitted to different long-term amendments, allowing for some conclusions on the possible contamination of adjacent water resources by contaminated soils. The work here presented constitutes a multidisciplinary approach to the environmental occurrence of psychiatric pharmaceuticals and gives a fair contribution to this area of concern.
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Reshat, Reshat. "Evaluating the genotoxic potential of oligonucleotide pharmaceuticals." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/10928.
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According to regulatory guidelines, routine genotoxicity tests are not appropriate for biotechnology derived pharmaceuticals, including oligonucleotide based therapeutics, as they are not expected to interact with genomic DNA. However, reports of oligonucleotides capable of binding duplex DNA in a sequence specific manner to form triple-helix (triplex) or displacement-loop (D-loop) structures that in turn cause mutation have raised concern. The European Medicines Agency (EMA) has questioned the capability of antisense oligonucleotide (ASO) therapeutics to form such structures at genomic DNA. Additionally, concern has been expressed regarding the fate of chemically modified ASO degradation products (nucleotide analogues). It is well established that non-canonical antiretroviral nucleoside analogues, employed in antiretroviral therapy, result in gross chromosome aberrations following incorporation into genomic DNA. This study has addressed these concerns by evaluating the genotoxic potential of a triplex forming oligonucleotide (TFO) and a D-loop forming ASO targeting genomic DNA. Furthermore, the incorporation efficiency and genotoxicity of nucleotide analogues derived from ASO degradation was investigated. Data presented here demonstrate a TFO targeting genomic DNA was not capable of inducing mutation above the detection limit of this assay. However, a biologically active ASO molecule induced sequence specific mutation ~4.4 fold above control in a system where RAD51 protein expression was induced. Additionally, DNA polymerase was capable of incorporating various ASO derived nucleotide analogues into a primed DNA template with reduced efficiency. Treatment with phosphorothioate nucleotide analogue, one of the most common chemical modifications used in ASO design, induced mutation ~100 fold above control. To conclude, ASO and their putative degradation products appeared to be capable of off-target mutagenesis providing favourable conditions were met. However, as genotoxicity data has been presented for a single ASO and nucleotide analogue, it seems plausible to suggest this work can provide a foundation to test future ASO therapeutics and putative degradation products.
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Zhong, Hai Hurley Jeremiah E. "Three essays in the economics of pharmaceuticals." *McMaster only, 2006.
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Lundberg, Robert. "Preliminary Investigation into Quantitation of Pharmaceuticals in Lake Victoria Sediments : Development of a Method for Analysis of 11 Pharmaceuticals." Thesis, Linköpings universitet, Tema Miljöförändring, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-176660.
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Although Lake Victoria is threatened by pollution there is a lack of knowledge about pharmaceuticals contaminants drained into the lake from large cities bordering the lake. Hence, the purpose of this project was to develop, validate and apply a method for analysis of pharmaceutical compounds accumulating in the Lake Victoria sediments. A simple quantitative method for 11 pharmaceuticals combining accelerated solvent extraction, solid phase extraction, trimethylsilylation derivatization, and gas chromatography mass spectrometry was developed, partly validated, and applied to 18 surface sediments and a sediment core dated using the 210Pb method. The results showed the presence of the pharmaceuticals estriol, gemfibrozil, metoprolol, ketoprofen, naproxen, 17α-ethinylestradiol and estrone concentrated around the regions Napoleon Gulf and Thurston Bay with accumulation rates decreasing towards the top of the sediment core. Nonetheless, a randomness in the distribution of these compounds behooves a systematic assessment investigating not only the provenance of these compounds but also further investigations to errors meaning that this study should be treated as a preliminary investigation.
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Shamal, Anmol. "The Pharmaceutical Industry And Marketing." Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1621703208673048.
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Worling, P. M. "Pharmaceutical wholesale distribution : The influence of the National Health Service and growing market competition on the development of the wholesale distribution of pharmaceuticals in the United Kingdom." Thesis, University of Bradford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381043.
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Pedrouzo, Lanuza Marta. "Pharmaceuticals and personal care products in environmental waters." Doctoral thesis, Universitat Rovira i Virgili, 2010. http://hdl.handle.net/10803/9058.
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En la presente Tesis Doctoral se han desarrollado diferentes métodos analíticos para la determinación de pharmaceuticals and personal care products (PPCPs) en aguas medioambientales. El término PPCPs engloba todos los fármacos, drogas de abuso, hormonas y los excipientes activos incluidos en productos de uso personal, así como los metabolitos, conjugados y sub-productos de transformación. Los métodos desarrollados han estado basados en extracción en fase sólida o extracción con barras magnéticas agitadoras seguidos de la cromatografía líquida acoplada a la espectrometría de masas o de masas en tándem. Debido a los bajos límites de detección alcanzados, estos métodos se pudieron aplicar a la monitorización de estos compuestos en diferentes plantas depuradoras del área de Tarragona, donde la información al respeto era inexistente. Debido a que el principal destino de las aguas residuales son los ríos, se analizaron aguas del Ter, Llobregat y Ebro. Para completar el estudio, la presencia de PPCPs fue determinada en aguas de consumo.In the framework of the present Doctoral Thesis different analytical methods have been developed to determine pharmaceuticals and personal care products (PPCPs) in environmental waters. The term PPCPs cover all the pharmaceuticals, drugs of abuse, hormones, the active compounds included in personal care products, and also metabolites, conjugates and transformation sub-products. The developed methods were based on solid-phase extraction and stir bar sorptive extraction followed by liquid chromatography coupled to mass spectrometry and tandem mass spectrometry. Achieving the low limits of detection, these methods could be applied to the monitoring of these compounds in different sewage treatment plants from Tarragona Region, where not data were available. The PPCPs resulting in the effluent sewage waters can achieve rivers. Therefore, waters from three rivers: Ter, Llobregat and Ebro were analyzed. To complete the study, also drinking water was analyzed to determine PPCPs.
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Gibson, Sara Nichols. "Oxidation of pharmaceuticals and personal products by permanganate." Thesis, Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/33870.
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Pharmaceuticals and personal care products (PPCPs) are widely used, resulting in trace amounts being detected in the aquatic environment. This presence is of human health and ecological concern and it is necessary to determine the best methods to eliminate them from our waters. The oxidation of PPCPs by permanganate was evaluated using a spectrophotometer to monitor permanganate reduction. Thirty-nine compounds were chosen to represent numerous classifications, including beta blockers, cephalosporins, fluoroquinolones, macrolides, non-steroidal anti-inflammatory drugs, phenol structures, polypeptides, sulfonamides, tetracyclines, and triazines. The reactivity of each compound was determined by measuring the absorbance of permanganate over time as it reacted with an excess of the compound. The absorbance data was fit to a pseudo-first-order reaction model that accounted for the growth of manganese dioxide colloids. The most reactive groups that reduced permanganate within minutes at pH 7.0 were the cephalosporins, phenol structures, and tetracyclines. The majority of the remaining pharmaceuticals and personal care products were moderately or weakly reactive (reducing permanganate within hours). Caffeine, carbadox, monensin, simetone, and tri(2-carboxyethyl)phosphine were poorly reactive (reducing permanganate over days). Metoprolol was the only selected compound that was determined to be potentially non-reactive (no reaction after 1 day). Polarizability and refractive index of the organic compounds showed significant positive correlations (R-squared > 0.50) with the first-order reaction rates for non-steroidal anti-inflammatory drugs and the phenol structures group. The half-life of each PPCP was determined based on a typical dosage of permanganate used for pre-oxidation. Eleven of the thirty-nine PPCPs had a half-life of less than thirty minutes (a typical contact time), indicating that oxidation by permanganate may be a viable option. There are many opportunities for further research in this area, including investigating more PPCPs, physicochemical property correlations, and the impact of water quality conditions
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Campbell, Alison June. "The behaviour of pharmaceuticals in anaerobic digester sludge." Thesis, University of Portsmouth, 2013. https://researchportal.port.ac.uk/portal/en/theses/the-behaviour-of-pharmaceuticals-in-anaerobic-digester-sludge(995bec06-33fd-4c74-96a3-db4aba5a1c30).html.
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Pharmaceuticals are biologically active compounds that may be consumed in hundreds of tonnes per year, and which are excreted into municipal sewerage systems. Many pharmaceuticals persist during sewage treatment, and significant environmental risk has been linked to incomplete removal of pharmaceuticals. Evaluation of this risk is important and should be as representative as possible, taking into consideration all significant exposure routes and removal processes. Sludge treatment processes are of particular interest because they offer a final opportunity for the removal of persistent compounds before the disposal of treated biosolids. During environmental risk assessment, it is currently assumed that anaerobic sludge treatment results in insignificant removal of persistent and adsorptive compounds from sewage sludge. This project was undertaken to address whether this assumption is valid. This thesis describes research into the behaviour and fate of pharmaceuticals in anaerobic digester sludge, and examines how redox conditions influence removal efficiency. Nine commonly used pharmaceuticals (caffeine, cimetidine, fluoxetine, ibuprofen, metformin, naproxen, paroxetine, propranolol and salicylic acid) were selected for use based upon detection levels within sewage sludge and predicted anaerobic biodegradability. Initial experiments were conducted to identify toxicity to anaerobic microorganisms and anaerobic biodegradability. No toxicity to the microorganisms in anaerobic sludge was identified at ≤ 50 mg C L-1for any of the selected pharmaceuticals. The extent of removal in anaerobic sludge and the principal removal mechanism was found to vary between the selected pharmaceuticals. Metformin and salicylic acid were removed by 82 and 93% through mineralisation, respectively; naproxen was completely removed through primary biodegradation; fluoxetine, paroxetine and propranolol were removed by 92 and 96 and 55% due to adsorption, respectively. It was hypothesised that the removal of pharmaceuticals in anaerobic sludge through biodegradation and adsorption would be observed at varying rates under differing redox conditions. Test systems using headspace gas flushing and chemical amendment were evaluated for the control of redox conditions, with Eh measurements and DOC removal being used to indicate the stability of the system and its capacity for biodegradation. The addition of nitrate, sulfate and carbonate resulted in poised Eh values in the region of +200, -200 and -200 mV, respectively and 81, 78 and 74% removal of DOC, respectively. This methodology was subsequently used to evaluate the removal of naproxen, propranolol and fluoxetine under carbonate-, nitrate- and sulfate-amended conditions. Significant differences (p = 0.001) in the removal of naproxen through primary biodegradation were found to exist between different redox conditions. Naproxen was completely removed under control conditions, while 26, 98 and 61% removal was observed under nitrate- sulfate- and carbonate amended conditions, respectively. Some differences were observed in Kd values, however, redox amendment was found to have little influence upon the elimination of propranolol and fluoxetine through adsorption. It was identified from this work that pharmaceuticals within the aqueous phase degraded under anaerobic conditions as predicted, while pharmaceuticals associated with the biosolids were removed through adsorption and present a potential threat to the environment on the disposal of treated biosolids. This work supports the current industry assumption that anaerobic treatment of biosolids offers limited opportunity for the removal of adsorptive pharmaceuticals, and also found no evidence for their enhanced removal under redox-controlled conditions. While research described within this thesis increases knowledge of the behaviour of pharmaceuticals in sewage sludge under anaerobic conditions, data is presented for a limited range of test substances only, and further investigation into the behaviour of additional compound classes is recommended.
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Shama, Leslie Marie. "Risk Assessment of Plant-Based Pharmaceuticals and Biologics." Thesis, Montana State University, 2006. http://etd.lib.montana.edu/etd/2006/shama/ShamaL1206.pdf.
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Biotechnology is evolving to produce pharmaceutical proteins in plants. Plantbased pharmaceutical production creates concerns of exposure in an open environment and contamination of the food supply. Consequently, quantitative human health and ecological risk assessments were conducted for aprotinin, gastric lipase, and LT-B expressed in maize. A comparative, qualitative risk assessment was conducted for conventionally derived and plant-cell derived Newcastle disease virus vaccine. Effect and exposure scenarios were modeled for each quantitative risk assessment and each scenario was based on a tiered approach in which inadvertent exposure through ingestion were examined to determine a risk characterization of the plant-based pharmaceuticals. The qualitative Newcastle disease virus vaccine risk assessment characterized risks based on the potential exposures to the poultry being vaccinated, to humans administering the vaccine, and to non-target birds. For the human-health risk assessment, the dietary exposure evaluation model (DEEM) was used to estimate the inadvertent dietary intake of the pharmaceutical proteins in food. The ecological risk assessment used Monte Carlo simulations to evaluate the exposure of each protein in maize for four receptor species. The human-health risk assessments revealed that the most conservative scenario produced higher risk quotients (RQ's) than the other two scenarios. The difference in risks was attributable to the differences in toxic endpoints of the proteins. Although the protein expressions and dietary consumption were assumed to be the same, dietary risks between the proteins varied by more than 56,000 times. The human-health risk assessment revealed that risks will vary dramatically and depend on factors such as the specific pharmaceutical protein, protein expression, and exposure scenarios. The assessments reinforced the need for case-by-case assessments. The ecological risk assessment demonstrated that risks will vary between species and between proteins, based primarily on differences in toxic endpoint and consumption rates. It shows the utility of probabilistic, quantitative risk assessment methodologies and supports the human dietary risk assessment by demonstrating the importance of assessing risks from plant-based pharmaceuticals on a case-by-case basis. The qualitative assessment illustrated that fewer effects and contamination issues were associated with the use of the plant-cell derived Newcastle disease virus vaccine compared to conventionally derived vaccines.
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Aban, Kevin, and Jens Göst. "Analysis of transports with pharmaceuticals on Arlanda airport." Thesis, Linköpings universitet, Kommunikations- och transportsystem, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-98684.
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Rapporten syftar till att kartlägga och analysera dagens transportflöde av läkemedel på fraktområdet Cargo City på Arlanda. Cargo Center och APH Logistics är två fraktagenter som har sin verksamhet på Cargo City. Observera att Cargo City och Cargo Center inte har samma innebörd. Cargo Center och APH Logistics erbjuder genom nära samarbete transport och hantering av temperaturkänsligt gods, som till exempel läkemedel. Läkemedel är värdefullt gods som kräver särskild skötsel vid transport, hantering och förvaring. Det ställer stränga krav på samtliga aktörer i försörjningskedjan. Genom studiebesök och intervjuer har författarna kartlagt det befintliga flödet av läkemedel. SACT, ett åkeri och dotterbolag till Cargo Center, utför transporten av godset till Cargo City med nerkylda lastbilar. APH Logistics omlastningsterminal på Cargo City är temperaturkontrollerad, vilket innebär att läkemedelsgodset förvaras och lastats i flygcontainrar där. Det färdiglastade godset forslas sedan vidare till Cargo Centers terminal. Där sker vikt- och volymkontroll av godset, det registreras i olika datasystem och slutligen märks det med etiketter, så som flygfraktsedeln. Mycket av godset som hanteras på Arlanda körs med lastbil till andra flygplatser och destinationer runt om i Europa istället för att flygfraktas direkt från flygplatsen. Dessutom hanteras och förvaras inte allt läkemedelsgods under temperaturkontrollerade former. En totalkostnadsanalys har gjorts för att jämföra olika transportflödesscenarion. Dessutom har författarna identifierat den kundservice Cargo Center och APH Logistics bör erbjuda kunden. Den bygger på kvalitativa resonemang. Resultatet av rapporten är författarnas rekommendation till företagen av hur de bör gå tillväga i framtiden. Den ger både kortsiktiga och långsiktiga tips.
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Bonner, Jim C. Jr. "Extraction and purification of pharmaceuticals using supercritical fluids." Diss., Georgia Institute of Technology, 1998. http://hdl.handle.net/1853/11762.
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Ahmad, Kafeel. "Molecular farming : production of pharmaceuticals in transgenic tobacco." Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/10241.
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Molecular farming is an experimental application of biotechnology to modify crops in order to produce proteins and chemicals for medicinal and commercial interests. The vast majority in the developing world cannot afford the high cost of therapeutics produced by existing methods. We not only need to produce new therapeutics but also need to produce cheaper versions of the existing ones. Molecular farming could offer a viable option for this growing need for biopharmaceuticals. Part of the thesis deals with investigating ways to produce DesB30 form of human insulin in transgenic tobacco. The human insulin was synthesized in vitro as strep-tag II-mini-insulin fusion protein. Expression of mini-insulin by transgenic tobacco was confirmed by RT-PCR, western blotting and ELISA. However, sufficient levels of purified insulin could not be obtained to carry out further functional assays. Strategies for increasing the yield of insulin by transgenic tobacco are discussed and further increases in yield would need to be developed for this to become a viable and cost effective source of this important pharmaceutical. The second part of the thesis describes the production of a recombinant microbial polysaccharide in tobacco. Seven type 2 pneumococcal polysaccharide biosynthetic genes were expressed in a single tobacco plant, utilizing the plant Kex2 (Kexin protease 2) like protease system for multiple gene expression. Expression of these genes in transgenic tobacco was confirmed by RT-PCR and western blotting. Correct processing of the expressed proteins by the Kex2 protease system was confirmed. However, In planta production of type 2 polysaccharide could not be confirmed mainly as a result of high background from the wild type plant polysaccharide extracts. Strategies to overcome these issues are described. The usefulness of Kex2 protease system for multiple gene expression and metabolic pathways engineering is also discussed.
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Crisp, Jenna L. "Solvent-mediated polymorphism and characterisation of inhaled pharmaceuticals." Thesis, Loughborough University, 2011. https://dspace.lboro.ac.uk/2134/8494.
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The use of polar anti-solvents for the crystallisation of lactose from 10% (w/v) aqueous solutions has been investigated. Crystal growth was observed at 50-65% antisolvent content and showed a morphological transition from polyhedral to needle-like habit with increasing antisolvent content, which coincided with a polymorphic transition from alpha lactose monohydrate (t:a. H20) to beta lactose (L~). Where anhydrous dehydrating antisolvents were employed such a~ methanol and ethanol, evidence of La. H20 dehydration to form stable anhydrous alpha lactose (Las) was also observed at 95% antisolvent content. Powder X-ray diffraction (PXRD) analysis of the samples highlighted the preferred orientation effects exhibited by large crystals of this kind, indicating the difficulties experienced by the non-specialist when performing phase identification of lactose polymorphs by PXRD. Application of the same crystallisation procedures to a racemic mixture of the active pharmaceutical ingredient (API) salbutamol sulfate (SS) indicated that some conditions can promote the formation of solvated SS. Ethanolic suspensions of spray dried and micronised La. H20, with average particle size between 3 and 200~m, were prepared by static and reflux methods and compared with sub-micron lactose (SML) suspension prepared by a high pressure homogenisation approach. Dehydration behaviour as a function of time was investigated by 13C CP MAS NMR spectroscopy and in all cases, indicated that suspensions contained Las. Several approaches were employed to remove ethanol from these suspensions and the products were analysed by PXRD and scanning electron microscopy (SEM). For samples with mean particle size greater than one micron, Las was retained on removal of the ethanol, although differences in the morphology and particle size of the crystals were apparent. These data imply that while SML is stable under dry conditions it is more susceptible to rehydration than standard Las with particle size between 3 and 200~m. in-situ 13C CP MAS NMR spectroscopy, employing hand-made glass inserts, was used to investigate the dehydration behaviour of La. H20 to Las in ethanolic suspension. Strong ethanol 13C resonances were observed for some samples, indicating a liquid-solid interaction between the ethanol and lactose surface. Replacement of ethanol with anhydrous methanol, n-butanol and 3-methylbutan- 2-01 implied that the solvent mediated dehydration is sterically controlled. 13C CP MAS NMR studies of SS, fluticasone propionate (FP) and salmeterol xinafoate (SX) showed that both SS and FP exhibit very short relaxation times for a solid material (-2s). This liquid-like behaviour is particularly beneficial pharmaceutically, as these APls are often mixed with an excess of lactose in inhaled formulations. Lactose behaves as a typical crystalline solid, and therefore experiences significantly longer relaxation times (-360s). Signals from SS and FP were successfully isolated from lactose/API blends (98%/2%) simply by reducing the delay times used within the 13c CP MAS NMR experiment.
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Foumier, Romain. "Probing amorphous and crystalline pharmaceuticals systems using NMR." Thesis, Durham University, 2006. http://etheses.dur.ac.uk/2935/.
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The Ή and '3C solution-state NMR spectra of the three studied drug molecules (indomethacin, nifedipine and carbamazepine) were fully assigned. This led to the characterisation and assignment of the '3C CPMAS SSNMR spectra of the stable polymorphic forms of these molecules. The signal for the с-СІ carbon of indomethacin has been studied as a function of applied magnetic field, and the observed bandshapes have been simulated. A T(_1)(^H)and T(_1p)(^H) study was undertaken on the crystalline materials, as well as on the quench-cooled amorphous and PVP/drug co-melts. This was done in order to fulfill the aim of this research, i.e. to understand the difference in stability of the amorphous compounds and also to investigate the effect of the presence of PVP on the stability and mobility of the drug. It was shown that, under the conditions of the experiments, amorphous indomethacin did not recrystallise until 110 c, whilst in the case of nifedipine and carbamazepine the recrystallisation occurred at 70 c and 75 c respectively. It was also shown that in the case of the co-melts a transition occurs consistently between 65 c and 85 c for the three materials and this seems to be due to the Tg of the co-melts. The comparison of the T(_1)(^H)and T(_1p)(^H) data for the different states showed that amorphisation increased the mobility of the sample, this being more pronounced for carbamazepine and nifedipine than for indomethacin, and also that the co-melts were more stable and slightly more mobile than the amorphous compounds. The comparison of the relaxation data between the pure compounds showed that amorphous indomethacin was more stable than the other two amorphous drugs as slope changes occurred for the latter at a temperature below Tg, whilst this happens at or around Tg for amorphous indomethacin.
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Christopher, Elizabeth Anne. "Solid-state NMR study of polymorphism in pharmaceuticals." Thesis, Durham University, 1993. http://etheses.dur.ac.uk/5752/.
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This thesis is concerned with attempts to establish solid-state NMR as a complementary technique to X-ray crystallography for providing information on crystal structure, i.e. information regarding conformation, packing and inter- or intra-molecular interactions. Methods of assigning the solid-state NMR spectrum have been used which rely upon (^1)H-(^13)C dipolar interactions and upon the shielding anisotropy experienced by the nuclei. Single pulse experiments have also been used to identify solvate molecules. Of particular importance, the anisotropy and asymmetry have been found for a number of steroids, and the values used to assign the high frequency region of the spectrum. This has enabled chemical shifts to be linked to the hydrogen bonds that are present. Thus, the mode of hydrogen bonding can be predicted in forms of cortisone acetate for which the crystal structure is not available. Chemical shifts have also been linked with the conformation of the D ring. In this way, important crystallographic information has been gleaned from the solid-state NMR spectrum. The effect of the formation of hydrogen bonds upon the shielding tensor components of carbonyl and ester carbons has been studied, and found to cause a high frequency shift in δ22, which is probably oriented along the C=0 bonds. This leads to a high frequency shift in the isotropic chemical shift. The effect of the spinning speed upon the centreband intensity of a peak as the anisotropy and asymmetry are varied has been investigated. It has been found that at low spiiming speeds, the centreband intensity does not vary in a simple fashion. Thus it is recommended that full shielding tensor analysis is performed. The effect of the spinning speed on the sample temperature has also been studied. Results show that at low spinning speeds (up to 2 kHz) there is sample cooling as the spinning speed increases (attributed to the Joule -Thompson effect). But at higher spinning speeds (above 2 kHz) then there is sample heating as the spinning speed increases. The importance of this result is discussed. The effect of quadrupolar nuclei (35C1 and (^14)N) upon the spectrum of a spin-(^1)(_2) nucleus ((^13)C) has been studied. In favourable cases, the anisotropy in the spin-spin coupling constant has been found, whilst in other cases, the sign and magnitude of the quadrupolar coupling constant have been obtained. The broadening of resonances of carbon atoms adjacent to quadrupolar nuclei has been valuable in assigning the solid-state NMR spectra. The broadening effect has also been observed at more distant sites. It has not been possible to distinguish the effects of (^37)C1 and (^35)C1 on the carbon spectra of chlorine containing steroids.
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Wilburn, Kristopher Ray. "The business case for continuous manufacturing of pharmaceuticals." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/59190.
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Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering; in conjunction with the Leaders for Global Operations Program at MIT, 2010.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 52-53).
Manufacturing in the pharmaceutical industry is presently characterized as a batch production system, which has existed in its current form for decades. This structure is the result of historical regulatory policy as well as the conservative nature of the industry. Recent clarification by US and European regulatory bodies has opened the possibility to new approaches to the manufacturing process. This combined with changes in the market for the pharmaceutical industry has accelerated the rate at which new manufacturing technologies are explored. Continuous manufacturing is a paradigm shift in the pharmaceutical industry manufacturing structure, encompassing several new technologies and systems. The business impact of continuous manufacturing has not been well defined. This assessment aims to compare a continuous manufacturing process to a batch manufacturing process for a particular Novartis product. The product has an established batch production process. Cost estimates and the continuous process cost is estimated using a four-step process: defining the process flow, performing the material balance, estimating the capital costs, and estimating the operating costs. This analysis shows that for the particular Novartis product considered, a continuous process is an improvement over the batch process in four performance characteristics: capital investment, operating cost, throughput time, and working capital requirement.
by Kristopher Ray Wilburn.
S.M.
M.B.A.
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Qureshi, Zaina Parvez. "Market Discontinuation of Pharmaceuticals in the United States." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1250572741.
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Xiao, Ruiyang. "Sonochemical Degradation of Pharmaceuticals and Personal Care Products." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1338345410.
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