Dissertations / Theses on the topic 'Pharmaceutical processes'
To see the other types of publications on this topic, follow the link: Pharmaceutical processes.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Pharmaceutical processes.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Scarr, James Richard Hadley. "Pharmaceutical development processes." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1446773/.
Full textAbstract:
The process of developing pharmaceuticals requires expertise from numerous different scientific areas. Four separate studies have been undertaken on Pharmaceuticals Testing, Process Development, Business Strategy and Process Validation within this industry. New pharmaceuticals generally require multi-step reactions, which increasingly feature the involvement of biological synthesis to improve the optical purity and thus efficacy and safety of the drug. Two of the problems with employing biological synthesis are the high level of inhibition observed and the potential difficulty with which these batch based reactions are combined with semi-continuous chemical synthesis. The first study characterises the inhibition of CHMO, a promising oxygenase enzyme, with the aid of flow cytometry using different systems: o A range of substrates, based around the natural substrate cyclohexanone but with differing ring size and increasing chain length. o Different CHMO catalysed reactions - isolated enzyme, free cell and immobilised whole cell. As expected, reactions with CHMO expressed in E. coli TOP 10 [pQR239] in their immobilised form reduced the observed reaction rate. Unexpectedly, for the more rapidly converted substrates (generally those closest to cyclohexanone), immobilisation was found to increase the inhibition observed. It has been postulated that this is due to an oxygen shortage for maintaining cell metabolism and a time based inhibitory effect. Advantages of immobilised cells are that they can be rapidly removed from the reaction broth allowing greater integration with other processes and can be recycled for multiple re-use. To facilitate their industrial use, the large scale production of immobilised whole cells is required. Whilst immobilised cell reactions are industrially employed, how such large quantities of immobilised cells are produced is yet to be reported. The feasibility of immobilisation of oxygenase expressing cells has been assessed in this first study, using the flow cytometry as a tool for assessing cell damage in the key step of cell separation. Within the pharmaceutical development process drug molecules are rigorously tested in clinical trials. However the metabolites likely to be produced in the body, which may be active (and preferable drug candidates to the parent molecule) or toxic (and thus responsible for the failure of the drug in the final stages of clinical trials) are often ignored. Within the human body the oxygenase enzymes Cytochrome P450s (CYPs) are responsible for the primary metabolism of more than 90% of drugs. The second study assesses different methods of identifying the CYP responsible for metabolism and discusses the importance of being able to produce gram scale quantities of metabolites. This study indicated that the best currently feasible option of CYP identification is the employment of Bactosome (individual CYP enzymes expressed in bacteria) with a selective inhibitor pre-screen. The scientific complexity of the pharmaceutical development process makes effective strategic planning and decision making difficult. Whilst the necessity of business plans to enable companies to secure finance has helped scientists to gain an understanding of their market and associated business risks, business decisions such as when to invest and how much, often rely solely on the company's tolerance of risk, collective intuition and experience. The third study investigates the business strategy of the pharmaceutical development process. StrategyDynamics modelling has been employed to create a living model of a start-up contract research organisation. The model demonstrates the advantages of being able to predict key resource bottlenecks, contrast different business decisions such as growth strategy and plan for future events and changes in technology and markets. This modelling can potentially save companies from expensive trial and error approaches and help to manage risk. Regulatory pressure within the pharmaceutical development industry and the importance of validation is increasing. In the fourth study the application of Process Validation to the areas of pharmaceutical development process in the first three studies are investigated. For CHMO biocatalysis the reproducibility of immobilised experiments was assessed, for drug metabolite production the importance of change validation, i.e. assay robustness, was determined and for the Strategy Dynamics modelling an approach to validating the model has been detailed.
2
Hussain, M. S. H. "Magnesium stearate lubrication in pharmaceutical processes." Thesis, University of Bradford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233659.
Full text
3
Johnson, David Benjamin. "Integrated design under uncertainty for pharmaceutical processes." Thesis, University College London (University of London), 2003. http://discovery.ucl.ac.uk/1383052/.
Full textAbstract:
in pharmaceutical process development there is frequently a large element of process uncertainty since knowledge of the mechanisms of production and separation is often limited. The overall objective of this thesis is the development of a general methodology which combines process modelling with uncertainty techniques to support the process development of complete integrated sequences. In a structured approach the uncertainty can be managed and improved process performance may be obtained. The major concept of this work is the integration of stochastic methods into a general framework for batch and continuous process models, consisting of two main parts. The first combines systematic modelling procedures with Hammersley sampling based Uncertainty Analysis and a range of sample-based Sensitivity Analysis techniques, used to quantify predicted performance uncertainty and identify key uncertainty contributions. In the second, a stochastic optimisation approach is employed to solve different problems under uncertainty. The methodology was implemented on two case studies. The first study investigated a batch reactor process. Some undesirable performance characteristics were observed when the published nominal optimal isothermal operating policy was implemented in the uncertain system. It was found that a robust operating policy significantly improved the total process time characteristic but not the impurity content and an alternative non-isothermal policy strategy would be a better option. The second study investigated a complete process sequence. As models developed with incoming data, uncertainty in the reaction and crystallisation parameters were critical to the endpoint quality criteria. Expected performance was improved by considering the propagation of uncertainty in the complete process. Four different flowsheets were compared, considering profitability and control tolerance criteria under uncertainty. The case study results indicate the importance in considering uncertainty systematically and quantitatively when conventional modelling techniques are employed. The methodology showed the opportunity to improve process performance potential and provide more realistic information to support pharmaceutical process development.
4
Ricard, Francois-Xavier. "Application of electrical resistance tomography to pharmaceutical processes." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417797.
Full text
5
Zolotariov, Eyal. "Modelling and optimisation of pharmaceutical formulations and processes." Thesis, King's College London (University of London), 2001. https://kclpure.kcl.ac.uk/portal/en/theses/modelling-and-optimisation-of-pharmaceutical-formulations-and-processes(0bc4835e-7920-4bca-9f87-f816770704ac).html.
Full text
6
HAUSMAN-MANNING, DEBRA SUE. "APPLICATION OF PROCESS ANALYTICAL TECHNOLOGY TO PHARMACEUTICAL PROCESSES." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1108838053.
Full text
7
Muller, Damian Christian. "Investigating the influences of validation on pharmaceutical manufacturing processes." Thesis, Nelson Mandela Metropolitan University, 2007. http://hdl.handle.net/10948/566.
Full textAbstract:
This investigation attempts to examine the influences of validation on pharmaceutical processes especially at a new manufacturing facility that has to meet international requirements, and fulfil a cost effective business strategy. At Aspen Pharmacare, a pharmaceutical organisation, there are two manufacturing facilities situated adjacent to each other, one new and one old. The new facility creates ideal opportunities to supply products to local and international markets. The investigation compares legal requirements from local and international regulatory authorities. Validation and qualification practices as well as the problems encountered during the different phases are discussed. Particular attention is given to the validation approach at the new Aspen facility. Problems and proposed solutions relating to the design review, installation, operational, and performance qualification are discussed. Validation of analytical methods for cleaning analysis, cleaning validation of equipment, and optimisation of some tablet manufacturing processes are described. Statistical evaluations of analytical results are included to find the optimum conditions for integrating new personnel with new processes and equipment. A business model reviews the cost of non-conformances of the enalapril maleate 10 mg tablets manufactured at the two manufacturing facilities. Finally the dissertation proves that validation is not only a regulatory requirement but that it also provides benefits such as adding value to the business, and ultimately reducing the cost of medicines.
8
Burke, Keeley. "The use of statistics in understanding pharmaceutical manufacturing processes." Thesis, University of Newcastle upon Tyne, 2016. http://hdl.handle.net/10443/3096.
Full textAbstract:
Industrial manufacturing processes for pharmaceutical products require a high level of understanding and control to demonstrate that the final product will be of the required quality to be taken by the patient. A large amount of data is typically collected throughout manufacture from sensors located around reaction vessels. This data has the potential to provide a significant amount of information about the variation inherent within the process and how it impacts on product quality. However to make use of the data, appropriate statistical methods are required to extract the information that is contained. Industrial process data presents a number of challenges, including large quantities, variable sampling rates, process noise and non-linear relationships. The aim of this thesis is to investigate, develop and apply statistical methodologies to data collected from the manufacture of active pharmaceutical ingredients (API), to increase the level of process and product understanding and to identify potential areas for improvement. Individual case studies are presented of investigations into API manufacture. The first considers prediction methods to estimate the drying times of a batch process using data collected early in the process. Good predictions were achieved by selecting a small number of variables as inputs, rather than data collected throughout the process. A further study considers the particle size distribution (PSD) of a product. Multivariate analysis techniques proved efficient at summarising the PSD data, to provide an understanding of the sources of variation and highlight the difference between two processing plants. Process capability indices (PCIs) are an informative tool to estimate the risk of a process failing a specification limit. PCIs are assessed and developed to be applied to data that does not follow a standard normal distribution. Calculating the capability from the percentiles of the data or the proportion of data outside of the specification limits has the potential to generate information about the capability of the process. Finally, the application of Bayesian statistical methods in pharmaceutical process development are investigated, including experimental design, process validation and process capability. A novel Bayesian method is developed to sequentially calculate the process capability when data is collected in blocks over time, thereby reducing the level of noise caused by small sample sizes.
9
Beyer, Andreas [Verfasser], and Claudia [Akademischer Betreuer] Leopold. "Solid state transformations during pharmaceutical processes / Andreas Beyer ; Betreuer: Claudia Leopold." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2020. http://d-nb.info/120967601X/34.
Full text
10
Tumuluri, Venkat S. "Quantitation of pharmaceutical formulations and monitoring of pharmaceutical processes using process analytical technology techniques : near infrared and Raman spectroscopy /." Full text available from ProQuest UM Digital Dissertations, 2007. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1414121171&SrchMode=1&sid=7&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1220637804&clientId=22256.
Full text
11
Fung, Ho Ki. "Synthesis and development of manufacturing processes for biopharmaceuticals /." View Abstract or Full-Text, 2003. http://library.ust.hk/cgi/db/thesis.pl?BIEN%202003%20FUNG.
Full text
12
Stewart, David, and Stacy D. Brown. "Active Learning Processes Used in US Colleges of Pharmacy." Digital Commons @ East Tennessee State University, 2010. https://dc.etsu.edu/etsu-works/5296.
Full text
13
Wong, Chris Wai Leung. "Data integration for the monitoring of batch processes in the pharmaceutical industry." Thesis, University of Newcastle Upon Tyne, 2007. http://hdl.handle.net/10443/610.
Full textAbstract:
Advances in sensor technology has resulted in large amounts of data being available electronically. However, to utilise the potential of the data, there is a need to transform the data into knowledge to realise an enhanced understanding of the process. This thesis investigates a number of multivariate statistical projection techniques for the monitoring of batch fermentation and pharmaceutical processes. In the first part of the thesis, the traditional performance monitoring tools based on the approaches of Nomikos and MacGregor (1994) and Wold et al. (1998) are introduced. Additionally, the application of data scaling as a data pre-treatment step for batch processes is examined and it is observed that it has a significant impact on monitoring performance. Based on the advantages and limitations of these techniques, an alternative methodology is proposed and applied to a simulated penicillin fermentation process. The approach is compared with existing techniques using two metrics, false alarm rate and out-ofcontrol average run length. A further manufacturing challenge facing the pharmaceutical industry is to understand the differences in the performance of a product which is manufactured at two or more sites. A retrospective multi-site monitoring model is developed utilising a pooled sample variancecovariance methodology of the two sites. The results of this approach are compared with a number of techniques that have been previously reported in the literature for the integration of data from two or more sources. The latter part of the thesis focuses on data integration using multi-block analysis. Several blocks of data can be analysed simultaneously to allow the inter- and intra- block relationships to be extracted. The methodology of multi-block Principal Component Analysis (MBPCA) is initially reviewed. To enhance the sensitivity of the algorithm, wavelet analysis is incorporated within the MBPCA framework. The fundamental advantage of wavelet analysis is its ability to process a signal at different scales so that both the global features and the localised details of a signal can be studied simultaneously. Both existing and the modified approach are applied to data generated from an experiment conducted in a batch mini-plant and that was monitored by both physical sensors and on-line UV-Visible spectrometer. The performance of the integrated approaches is benchmarked against the individual process and spectral monitoring models as well as examining their fault detection ability on two additional batches with pre-designed process deviations.
14
Bell, Charlotte. "Advanced analytical and microbial methods for biopharmaceutical and pharmaceutical products and processes." Thesis, University of Newcastle upon Tyne, 2014. http://hdl.handle.net/10443/2736.
Full textAbstract:
In recent years, pharmaceutical research has begun to shift from the development of small molecule chemical entities, to complex high value, low volume biologics. The cost of batch losses or product recall due to the presence of microbial, chemical or physical contaminants can have serious implications for a business. It is therefore important that as the complexity of pharmaceutical products increases, the techniques utilised in the analysis and characterisation of these products and their excipients also moves forward, thereby ensuring product quality and patient safety. This research explores three areas of analysis and characterisation relating to pharmaceutical products: microbial testing; oxidative stability testing and container integrity testing. The detection and identification of microbiological contamination using traditional microbial methods (TMMs) have a number of limitations such as long testing times and reliance on subjective assessment leading to operator error. More recently developed rapid microbial methods (RMMs) have been designed to overcome these limitations and their uptake would enable microbial testing to align with the process analytical technology (PAT) approach to process monitoring and control. A review of available techniques and those implemented by a large pharmaceutical company, GlaxoSmithKline has highlighted that a number of RMMs are being utilised, but their widespread adoption in the pharmaceutical industry faces several barriers including: economic and financial; institutional; legislative and regulatory; and technical. Another important area of pharmaceutical product analysis is that of oxidative stability testing. A comparison was undertaken of two machines for measuring oxidative stability (the Rancimat (Metrohm)) and the ACL Instrument (ACL Instruments, Switzerland) to investigate their performance and assess their applicability for the testing of pharmaceutical excipients. The testing of corn oil, selected as a model substance, revealed a strong correlation between the results from the two machines. An aspect of oxidative stability testing is concerned with residual levels of peroxides therefore the ACL Instrument was compared to iodometric titration, a highly empirical traditional approach, for the quantification of peroxides in corn and Menhaden oil. Good correlation was found between peroxide levels measured by the two methods, but the results from the ACL Instrument showed a dependence on oil type, meaning that a standard would be required each oil type. Additional testing was carried out on polysorbates, pharmaceutical excipients that are known to pose stability issues in final formulations, due to containing residual amounts of peroxides. Using the ACL Instrument it was possible to detect differences in oxidative stability between grades and types of polysorbate. It was not possible to discriminate between batches of the same grade. The final testing that is carried out on pharmaceutical products stored in glass vials, is container integrity testing. High voltage leak detection (HVLD) is one method utilised and concerns exist as to whether the high voltages present can cause ozone formation in the container headspace, leading to degradation of the drug product. A method involving potassium indigo trisulphonate was developed for the detection of ozone and a test protocol implemented. This approach showed that ozone was produced in containers with a low fill volume, but at a very low concentration and hence it should not affect the stability of the final product. The research carried out in this thesis has drawn together evidence on RMMs; furthered understanding of the applicability of oxidative stability testing for pharmaceutical excipients; and has highlighted the importance of investigating the effect of container integrity testing methods on the final pharmaceutical product.
15
Beyer, Andreas [Verfasser], and Claudia S. [Akademischer Betreuer] Leopold. "Solid state transformations during pharmaceutical processes / Andreas Beyer ; Betreuer: Claudia S. Leopold." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2019. http://d-nb.info/1194165087/34.
Full text
16
Stewart, David, Stacy D. Brown, Cheri W. Clavier, and Jarrett Wyatt. "Survey of Active Learning Processes Used in US Colleges of Pharmacy." Digital Commons @ East Tennessee State University, 2011. https://doi.org/10.5688/ajpe75468.
Full textAbstract:
Objective. To document the type and extent of active-learning techniques used in US colleges and schools of pharmacy as well as factors associated with use of these techniques.
Methods. A survey instrument was developed to assess whether and to what extent active learning was used by faculty members of US colleges and schools of pharmacy. This survey instrument was distributed via the American Association of Colleges of Pharmacy (AACP) mailing list.
Results. Ninety-five percent (114) of all US colleges and schools of pharmacy were represented with at least 1 survey among the 1179 responses received. Eighty-seven percent of respondents used active-learning techniques in their classroom activities. The heavier the teaching workload the more active-learning strategies were used. Other factors correlated with higher use of active-learning strategies included younger faculty member age (inverse relationship), lower faculty member rank (inverse relationship), and departments that focused on practice, clinical and social, behavioral, and/or administrative sciences.
Conclusions. Active learning has been embraced by pharmacy educators and is used to some extent by the majority of US colleges and schools of pharmacy. Future research should focus on how active-learning methods can be used most effectively within pharmacy education, how it can gain even broader acceptance throughout the academy, and how the effect of active learning on programmatic outcomes can be better documented.
17
Wang, You-Gan. "Contributions to the theory of Gittins indices : with applications in pharmaceutical research and clinical trials." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293423.
Full text
18
GIMENEZ, FLAVIA COSENTINO RAMOS. "PURCHASING AREA INTEGRATION ON MERGING AND ACQUISITION PROCESSES: CASE STUDY FROM THE PHARMACEUTICAL INDUSTRY." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2014. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=28086@1.
Full textAbstract:
O objetivo desta dissertação é a pesquisa das boas práticas e dos fatores críticos de sucesso, em processos de fusão e aquisição, para apoiar a análise da integração dos processos de compras de duas empresas do setor farmacêutico. Desde o surgimento das primeiras indústrias, este setor possui grande histórico de negociações nos processos de fusões e aquisições. O trabalho descreve e analisa as principais atividades de compra e as tecnologias utilizadas pela empresa compradora, as quais foram definidas como padrões na integração das empresas. Para que esta análise ocorra de forma completa, foi necessário a realização de pesquisas em temas complementares, considerados importantes para o entendimento de todo o processo da integração como: aspectos motivacionais da integração das empresas, boas práticas na gestão da cadeia de suprimentos relacionadas com a função compras, detalhamento das atividades do processo de compras e das tecnologias da informação de apoio. Foi feito um exame relacionando a prática com o referencial teórico, elucidando se a prática seguiu a teoria. A conclusão levou em consideração a crítica do processo da integração dos processos com sugestões para próximos casos e pesquisas na área.The focus of this dissertation is on the good practices research and the critical success factors for merging and acquisition processes, used as basis for a critical analysis of the purchasing integration processes of two companies from the pharmaceutical sector. Since the birth of the first industries, this sector has had many historical negotiations in the merging and acquisitions processes. The paper describes and analyzes the main activities of purchasing and the technologies used by the acquiring company, which were defined as standards in integrating businesses. In order to have a throughout analysis, other complementary subjects were analyzed. They were of great importance for the overview of the integration process such as: motivational aspects used on merging companies, the functional detailing of the purchasing process and the supporting information technology. An analysis correlating the theory with real practices was done to verify their similarities. The conclusion took in consideration the merging processes review with suggestions for next studies and researches in the area.
19
Feng, Ruili. "Synthesis and evaluation of pharmaceutical and fine chemicals processes for intensification and sustainability benefits." Thesis, University of Newcastle upon Tyne, 2018. http://hdl.handle.net/10443/4125.
Full textAbstract:
In the face of global competition and tighter safety and environmental regulations, the pharmaceutical industry is exploring new areas and technologies that could potentially bring about step change in process performance. Process intensification has the potential to improve early development by introducing new process options, which are capable of achieving green and sustainable benefits in production. In this thesis, the objective is to demonstrate the synthesis and evaluation of pharmaceutical processes for intensification and sustainability benefits. This is illustrated with two main processes - the amidation process and the ortho-lithiation process. Based on the experiences gained at the end of the case studies, a general framework that summarizes the approach to Process Intensification (PI) for pharmaceutical processes is developed. Firstly, the amidation process has been successfully intensified with the implementation of a number of PI options, which are proven feasible in lab-scale experiments. These options are represented in terms of three intensified cases - the intensified batch case, the continuous reaction case and the continuous process case, are compared to the batch base case. To compare their sustainability performance, the respective plants are designed at a hypothetical throughput of 3 tons per year. Overall, the intensified batch case provided the most benefits, with cost savings of up to 40%, and more than 70% improvements in total material efficiency and E-factor compared to the batch base case. This also indicates that batch mode operation in this particular process is more suitable than continuous mode. The second case study on the ortho-lithiation process consists of three parts. The first part investigates ortho-lithiation reaction in continuous flow reactors at ambient temperature. The findings demonstrated that the highest reaction yield of 99% was obtained in a T-reactor as a result of short residence time and good mixing. The Spinning Disc Reactor (SDR) also showed distinct advantage in handling this reaction with mild solid precipitation. The second part focuses on the comparison of the T-reactor, the SDR and the Stirred Tank Reactor (STR) based on the sustainability metrics. The results showed that the T-reactor process achieved 66% and 11% reduction in energy consumption and operating expenditure respectively as compared to the STR process. The last part of the ortho-lithiation process focuses on the study of the whole process including workup. To avoid dealing with inefficient separation process, consecutive reaction has been attempted by avoiding the isolation of ortho-lithiation crude product and directly transferring it into the next reactor for subsequent reaction. This is experimentally proven feasible and resulted in a greener process.
20
Chhatre, Sunil. "Evaluation of the financial and technical impacts of changing commercial-scale pharmaceutical manufacturing processes." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1445999/.
Full textAbstract:
Growing pressures in the pharmaceutical industry are driving the need to optimise processes used for the manufacture of drugs at commercial-scale, in order to improve cost of goods, product throughput and production times. Evaluating the impacts of process optimisation upon these metrics presents a challenge due to complexities and trade-offs that are often encountered when developing a typical bioprocess. Such factors have resulted in a range of novel simulation- and experimental- based techniques being developed which enable rapid, accurate and cost effective assessment of manufacturing options for commercial-scale production. This thesis proposes a combination of modelling and experimental methods for evaluating the business- and process-related impacts of implementing changes to pre-existing commercial-scale pharmaceutical manufacturing processes. The approaches are illustrated through an industrial case study, focusing upon a process operated by Protherics U.K. Limited for the manufacture of the FDA-approved rattlesnake anti-venom CroFab (Crotalidae Polyvalent Immune Fab (Ovine)). The novel methods developed and illustrated in this thesis include: Investigating the effects of process changes upon calculated yields and processing times within the production framework for a pre-existing FDA-approved bio-manufacturing process Evaluating the impacts of both developing and implementing process changes, combining output metrics into a single value to simplify the assessment Developing a multi-layered simulation methodology for the rapid and efficient evaluation of bio- manufacturing process options Applying advanced sensitivity analysis techniques to identify the most critical factors that influence product yield and throughput Evaluating a novel synthetic Protein A matrix for the recovery and purification of polyclonal antibodies from hyperimmunised ovine serum Developing decision-support software to aid the design of chromatography steps for antibody purification at industrial scale Demonstrating the utility of such models by application to data and constraints derived from a full-scale industrial facility.
21
Ku, Shaari Ku Zilati. "Coating uniformity on a pharmaceutical tablet an experimental study and finite volume modeling of droplet impact behavior /." Morgantown, W. Va. : [West Virginia University Libraries], 2007. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=5528.
Full textAbstract:
Thesis (Ph. D.)--West Virginia University, 2007.Title from document title page. Document formatted into pages; contains xv, 141 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 132-135).
22
Maclean, Aldritt Allister. "Comparison of two granulation processes with the view to reduce manufacturing cost." Thesis, Port Elizabeth Technikon, 2004. http://hdl.handle.net/10948/210.
Full textAbstract:
Aspen Pharmacare, one of the leading pharmaceutical manufacturers in South Africa has embarked on a programme of improving the production processes currently employed at their Port Elizabeth site. With the introduction of new technology at the site and the move towards globalization, it became imperative that Aspen remain competitive in the market. The product of interest in this research, Degoran Plus tablets, is one of the company’s leading brand sellers. Upon investigation, it became apparent that this product created opportunity for process improvement using the new technology. The manufacture of Degoran Plus entails granulation, compression and coating of the product. Most opportunity for improvement was possible in the granulation stage because of the laborious nature of the present process. Degoran Plus tablets had a history of analytical failures, especially with regard to the dissolution rate of the final product, as well as other quality related issues. The product was not considered to be a “through-runner”, which resulted in bad production output, due to continual repeats of not only analysis but also reworks in production. A strategic decision was taken to manufacture Degoran Plus using the Collette Gral granulator as the equipment offered superior mixing capability when compared to the Bear planetary granulator. It was assumed that the granulation process would result in more uniform distribution of the actives. Upon producing a better granule, a final product of superior quality would be attained. The validation protocol stipulates that three samples be taken and tested from the powder mix. Nine samples taken from granulated bulk are treated in the same manner. The validation protocol further stipulates that the first three batches manufactured utilise the new process, and tested according to the protocol. The results obtained from the analysis are evaluated statistically and a conclusion and recommendation were derived based on the evaluation.
23
Luthra, Satinder Singh. "Membrane reactors for phase transfer catalytic processes : waste minimisation in the fine chemicals / pharmaceutical industry." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415167.
Full text
24
Xie, Xiangzhong [Verfasser], Ulrike [Akademischer Betreuer] Krewer, and Sebastian [Akademischer Betreuer] Sager. "Sensitivity Analysis and Robust Design of Pharmaceutical Manufacturing Processes / Xiangzhong Xie ; Ulrike Krewer, Sebastian Sager." Braunschweig : Technische Universität Braunschweig, 2020. http://d-nb.info/1215293674/34.
Full text
25
White, Becky A. "The perceptions and beliefs of nurses using Knowledge Based Medication Administration (KBMA) bar code scanning processes in regards to patient safety." Thesis, Blessing-Rieman College of Nursing, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=1598248.
Full textAbstract:
Accurate and safe medication administration is an important aspect in the everyday care of the hospitalized patient. Patients put their trust and safety into the hands of those providing care and expect that care is provided in a safe and efficient manner. Nurses strive to provide high quality error free, patient care. With adult patients, medication administration accounts for 26% to 32% of hospital medication errors (Koppel, Wetterneck, Telles, & Karsh, 2008). Only 2% of administration errors are corrected before reaching the patient (Dwibedi, et al., 2011). Literature supports that knowledge based medication administration programs reduce medication administration errors (Fowler, Sohler, & Zarillo, 2009). The research question proposed was: What are the perceptions and beliefs of nurses using Knowledge Based Medication Administration (KBMA) bar code scanning processes in regards to patient safety? The design was a quantitative, descriptive study, using a convenience sample. The study site was west-central Illinois hospital. Data were collected and analyzed related to the perceptions and beliefs of the staff nurses using KBMA in regards to patient safety during medication administration processes. Staff nurses were surveyed using a Likert-like scale. Participants accessed the survey via My Netlearning which linked to Survey Monkey. Participation was voluntary and responses were anonymous. Future implications for quality improvement and education are considered.
26
Naicker, Krishnaveni. "An investigation into the introduction of process analytical technology, using near infrared analysis, to selected pharmaceutical processes." Thesis, Nelson Mandela Metropolitan University, 2007. http://hdl.handle.net/10948/577.
Full textAbstract:
Introduction: Process analytical technologies are systems for the analysis and control of manufacturing processes to assure acceptable end-product quality. This is achieved by timely measurements of critical parameters and performance attributes of raw material and in-process material and processes. The introduction of process analytical technology using near infrared analysis was investigated in three areas, namely incoming raw material analysis, blend uniformity analysis and moisture determination in the fluid bed dryer. Methodology: Incoming raw material identification - The FOSS XDS rapid content analyzer was used for the development of a NIR method for the identification and material qualification of starch maize and lactose monohydrate. Blend uniformity analysis – The SP15 Laboratory Blender fitted with near infrared probe was utilized for the study. Two types of blend experiments were designed to monitor the distribution of magnesium stearate (lubricant) in the blend, namely, a powder blend utilizing lactose monohydrate and a granule blend utilizing Ridaq® granule. Software methods were developed to monitor the standard deviation of the absorbance at the wavelengths that were specific for lactose monohydrate, Ridaq® granule and magnesium stearate. To confirm the prediction of end-point using near infrared, results were verified using an atomic absorption method for magnesium stearate. The blends were sampled at the selected time intervals corresponding to three states of the blend, namely, before end-point, at end-point and after end-point using a sampling plan. An additional six blends were conducted for the granule blend and sampled when the standard deviation had reached a value below 3 x 10-6 at the magnesium stearate wavelength at four consecutive data points (standard deviation value extrapolated from blends carried out to predetermined time intervals). Moisture determination in the fluid bed dryer – Moisture values for two products (Product A and Product B) were retrospectively collected from past production batches. A process capability study was conducted on the moisture values to determine if the current process was in a state of control. Results and Discussion: Incoming raw material identification – The algorithms used for the spectral library were able to distinguish between the raw materials selected. The spectral library positively identified the starch maize and lactose monohydrate samples that were not present in the library. The negative challenge with pregelatinised starch and tablettose demonstrated that the spectral library was able to differentiate between closely related compounds. Blend uniformity analysis – Blends sampled at the predetermined time intervals demonstrated a homogeneous state when the standard deviation of the absorbance was low and a non-homogeneous state when the standard deviation of the absorbance was high, thus near infrared prediction on the state of the blend was confirmed by the standard analytical methods. The series of Ridaq® granule and magnesium stearate blends sampled when the standard deviation was below 3 x 10-6 were homogeneous with the exception of one blend that was marginally out of specification. Blend durations were significantly lower than the standard blend durations used in the facility and ranged from 112 to 198 seconds. Moisture determination in the fluid bed dryer – From the process capability study of the two products it was noted that Product A is stable but can still be optimized while Product B is at a desirable state. The statistical evaluation of the moisture values for Product A and Product B demonstrated that the use of the product temperature to monitor the moisture gave consistent results. The current process is stable and capable of producing repeatable results although near infrared provides a means for continuously monitoring the product moisture and allows one to take action to prevent over-drying or under-drying. Conclusion: From the investigations conducted, it can be seen that there is definitely a niche for process analytical technology at this pharmaceutical company. The implementation is a gradual process of change, which may take time, probably several years (Heinze & Hansen 2005).
27
Rehder, Sönke Carsten [Verfasser], and Claudia Sabine [Akademischer Betreuer] Leopold. "Solid-state transformations induced by pharmaceutical processes during manufacturing / Sönke Carsten Rehder. Betreuer: Claudia Sabine Leopold." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2013. http://d-nb.info/1036729745/34.
Full text
28
Unger, Alexandra M. "An analysis of differences in glass cartridge siliconization parameters and processes for manufacturing of pharmaceutical cartridges." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/117961.
Full textAbstract:
Thesis: M.B.A., Massachusetts Institute of Technology, Sloan School of Management, in conjunction with the Leaders for Global Operations Program at MIT, 2018.Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, in conjunction with the Leaders for Global Operations Program at MIT, 2018.
Some pages printed landscape. Cataloged from PDF version of thesis.
Includes bibliographical references (pages 82-84).
The application of silicone inside of glass insulin cartridges helps reduce injection forces during drug delivery. This is important for a less painful patient experience. Insulin pen designs are increasingly reliant on consistent and repeatable injection forces as mechanized injection replaces manual injection. A minimum silicone layer thickness of 40nm is required to produce low gliding forces of approximately two Newtons with little variability. Differences seen in final gliding forces across production areas at Sanofi Insulin Frankfurt are small, but this variation makes it difficult to design for set-force mechanical injection. While the minimum silicone layer thickness required is established, how to achieve it consistently is less understood. This project looked at three insulin packaging lines at Sanofi Insulin Frankfurt that use different methods for siliconization. Differences between these lines were investigated in order to understand which parameters are the most important for creating an acceptable silicone layer thickness. First, each production line was mapped from loading of empty cartridges through the end of the heating tunnel, before insulin is packaged. Differences in the process were found in cleaning procedures, silicone application methods, and production settings. Points for potential variability were found at silicone mixing steps and during start/stop conditions. Lab experiments were developed to test cleaning procedures, heating time, standing time, air pressure of silicone blowout, and silicone concentration. Results from these experiments showed that some production processes have a greater effect than others on silicone layer thickness and subsequent gliding forces. Differences in cleaning procedures on each of the lines have little effect on overall silicone layer thickness and gliding forces. Time in the heating tunnel and standing time have a moderate effect. The largest effects were seen from silicone emulsion concentration and air blow out pressures in the flushing method of silicone application. The following recommendations are given to improve performance consistency across production areas: (I) standardize processes across production areas where possible, (2) reduce air pressure in the flushing process, and (3) eliminate process steps that can lead to several of these effects occurring in the same cartridge.
by Alexandra M. Unger.
M.B.A.
S.M.
29
Al-Hasnawi, Hassan. "Solar Heat in Industrial Processes : Integration of Parabolic Trough Solar Collectors Dairy Plants and Pharmaceutical Plants." Thesis, Umeå universitet, Institutionen för tillämpad fysik och elektronik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-125025.
Full textAbstract:
The industry sector accounts for a high share of the final energy consumption, with industries in EU-28accounting for a quarter of the final energy demand. Studies also show that 45 % of the industrial heatdemand in EU-27 is in a temperature range that can be supplied with present day solar collectors. Despitethis large potential, solar heat faces obstacles hindering its growth in the industrial sector. The mostsignificant obstacle is the low insight of the industrial system designs and energy demands. Those arecrucial factors for the feasibility and dimensioning of solar heating systems. Three case studies aretherefore conducted in dairy and pharmaceutical plants in order to review the most promising integrationpoints for parabolic trough solar collectors in terms of annual heat demand, temperature level andintegration effort. Two case studies are performed in dairy plants and one in a pharmaceutical plant, alllocated in Sweden. The analyses comprised reviewing energy mappings, process and instrumentationdiagrams of processes and boiler systems, and hourly energy demand data. Simulations have beencarried out with Polysun for the processes with hourly energy data available.Four integration points have been determined to be high priority solar heat integration points in dairyplants, when considering annual thermal energy demand, temperature levels and integration effort.Those are the low pressure steam line, heating of feedwater, clean in place systems and pasteurizers.Solar heat integration concepts have been presented for all the aforementioned heat sinks andsimulations have been conducted for the low pressure steam line and heating of feedwater. A significantamount of excess heat is produced as a result of fluctuating heat demands and peak solar heat productionhours. Further investigation should be carried out, in order to review the potential of supplying excessheat to other heat sinks. Despite the reviewed potential of the clean in place systems and pasteurizers,lack of the hourly energy demand has hindered further analyses of those systems. It is thereforerecommended to conduct energy measurements before taking further measures.Two integration points have been identified in the pharmaceutical plant, namely autoclaves andmultiple-effect distillers. Solar steam generation concepts have been presented for both processes. Theautoclaves are provided with 4,5 bar steam intermittently, as they work with batches and can have ondutyand off-duty intervals ranging from 3-30 minutes. The multiple-effect distillers are providedwith 7 bar steam, which is of rather high pressure for the solar collectors model on which thesimulations are based. The heat demand of the distillers is more or less constant.It was generally easier to acquire data for the integration points at the supply level. For instance, all heatsinks at the supply level had energy demand data available, contrary to the process level. This inclinesadditional focus on integration to the supply level, if the extent of the feasibility study is to be kept to aminimum.
30
Rehder, Sönke [Verfasser], and Claudia Sabine [Akademischer Betreuer] Leopold. "Solid-state transformations induced by pharmaceutical processes during manufacturing / Sönke Carsten Rehder. Betreuer: Claudia Sabine Leopold." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2013. http://d-nb.info/1036729745/34.
Full text
31
Sanderson, I. M. "The effect of formulation and maufacturing processes on the characterisitics of direct compression tablets." Thesis, University of Nottingham, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372670.
Full text
32
Siew, Weiming Eugene. "Application of membrane separation processes in the pharmaceutical industry : a study of process development for overcoming membrane limitations." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/14348.
Full textAbstract:
The prevalent business model in the pharmaceutical industry requires rapid and robust process development and flexible manufacturing processes. This work reports the attempts to develop structured procedures for membrane process development to meet these requirements. The Donnan Steric Pore Model, in conjunction with a computational molecular dynamics programme, was evaluated as tool for membrane performance predictions to circumvent the need for tedious membrane screening experiments. However, the computational effort required was too onerous, making experimentation more efficient than computational method at this stage. Process chemistry manipulation enabled the use of otherwise incompatible membranes for separation and reduced the time needed for membrane scoping. Firstly, through pH manipulation to selectively increase electrostatic sieving, the permeation selectivity of a membrane to 2 different solutes was changed. Secondly, a structured procedure for polyalkylation of an ‘anchor’ molecule to increase the steric hindrance of an organocatalyst was used to enable the total retention of the catalyst so that a single stage membrane recycling strategy for the catalyst could be enacted. Published membrane processes were analysed and found to lack robustness and to be too sensitive to slight deviations in membrane performance. Hence new membrane processes were devised to address these challenges. Firstly, a membrane cascade process was used to enhance the rejection of an active pharmaceutical ingredient (API) over the single pass membrane rejection. This cascade process was then used for concurrent API concentration and solvent recovery. Secondly, a permeable stripping cascade configuration was used for the removal of an excess reagent from an API to enable the excess loading of the reagent to increase the yield of the API. The membrane cascades benefited from enhanced reliability, increased productivity and improved robustness.
33
Abu, Bakar Mohd R. "Process analytical technology based approaches for the monitoring and control of size and polymorphic form in pharmaceutical crystallisation processes." Thesis, Loughborough University, 2010. https://dspace.lboro.ac.uk/2134/6436.
Full textAbstract:
Pharmaceutical crystallisation operation is often critical because it determines product properties, such as the crystal size distribution (CSD) and polymorphic form, that can influence the subsequent downstream operations and the product therapeutic performance. Driven by the United States Food and Drug Administration s (FDA) Process Analytical Technology (PAT) initiative and the Quality-by-Design (QbD) concept, the development of control approaches, which can improve the manufacturing of products with desired properties, has become of significant interest. This thesis presents the development and application of PAT-based approaches for the monitoring and control of pharmaceutical crystallisation operations that will ensure consistent production of active pharmaceutical ingredients (APIs) with the desired size and polymorphic form. The approaches utilised Lasentec focused beam reflectance measurement (FBRM) and attenuated total reflectance ultraviolet (ATR-UV) spectroscopy as the in situ monitoring and control tools. Crystallisations of the APIs that posses multiple polymorphs are both critical and challenging. This was illustrated in this work by the crystallisations of sulfathiazole polymorphs using literature methods. The processes were monitored using FBRM and ATR-UV spectroscopy to define the design range of the process parameters. The defined range could be used as a recipe to reproduce the same quality of crystals. The obtained crystals were characterised using various techniques (optical microscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetry, hot-stage microscopy (HSM), Fourier Transform infrared spectroscopy and powder X-ray diffractometry) to assess the success of the crystallisation processes. The combined results of the techniques showed that all methods were able to produce the desired pure polymorphs. As a contribution to the technique of investigating polymorphism, a combined approach of DSC-HSM with image analysis, was introduced. Results show the capability of the approach to provide a unique insight into the polymorphic transformations and thermal behaviour exhibited by the model compound. The novel direct nucleation control (DNC) approach was introduced to control the CSD. The approach utilises information on nucleation, provided by FBRM, in a feedback control strategy that adapts the process variables, so that the desired CSD of product is achieved. It also provides in situ fines removal through the operating policy, rather than having additional equipment and external recycle loops. The approach does not require concentration measurement and has the advantage of being a model-free approach, requiring no information on nucleation or growth kinetics in order to design an operating curve; the system automatically and adaptively detects the boundary of the operating curve. Experimental results, using glycine in water-ethanol mixture as a model system, show the benefits of DNC to produce larger crystals with narrower CSD compared to uncontrolled operations. The capability of seeded cooling crystallization with temperature cycling approach to control crystal size uniformity and polymorphic purity was evaluated. Using sulfathiazole in n-propanol and in water as model systems, the method was found to accelerate the growth and enhance the size uniformity of the crystals, in comparison with runs using a linear temperature profile, by promoting Ostwald ripening. Although the approach is conceptually capable of controlling polymorphic purity of a system, the effect of solvent-mediated nucleation/growth can be more dominant, as shown by the results of the experiments. The insights into this behaviour of sulfathiazole crystals were captured very well by the FBRM. The study also demonstrated the successful use of a simple non-linear function as a calibration model to relate temperature and absorbance data, obtained using the ATR-UV spectroscopy, to solute concentration during the crystallisation process. The effect of temperature cycling, performed during seeded cooling crystallisation, on the surface features of sulfathiazole crystals was investigated using FBRM and ex situ optical microscopy, SEM and atomic force microscopy. It was observed during the initial stage of the process, the heating phases produced crystals with smooth surfaces, whilst the cooling phases promoted growth of features on the surfaces. These changes detected by the FBRM as an increase in the number of coarse counts during heating and a drop during cooling. Laser beam spreading caused by the surface roughness, and signal/chord splitting due to sharp edges are offered as an explanation for the FBRM results. This shows the capability of the FBRM to provide useful information about the changes on the surface of the crystalline products. The information can be used to avoid problems in the downstream operations, or in the final product property due to variations in flowability and friability, which are influenced by the surface property.
34
BAYDUM, Valderice Pereira Alves. "Degradação de Propranolol em efluente modelo através de Processos Oxidativos." Universidade Federal de Pernambuco, 2012. https://repositorio.ufpe.br/handle/123456789/19024.
Full textAbstract:
Submitted by Caroline Falcao (caroline.rfalcao@ufpe.br) on 2017-06-07T17:41:34Z
No. of bitstreams: 2
license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5)
2012-Tese-ValdereicePereiraBaydum.pdf: 1681832 bytes, checksum: b5c9d3beb02641d325fe71ba0c2037f2 (MD5)Made available in DSpace on 2017-06-07T17:41:34Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) 2012-Tese-ValdereicePereiraBaydum.pdf: 1681832 bytes, checksum: b5c9d3beb02641d325fe71ba0c2037f2 (MD5) Previous issue date: 2012-11-23
A ocorrência de fármacos no meio ambiente tem se tornado um assunto de interesse nos últimos anos. Grande número desses compostos tem sido detectado em efluentes de estações de tratamento de esgoto (ETE) municipais, águas superficiais e, menos frequentemente, em águas subterrâneas e água potável em todo o mundo. Alguns dos efeitos adversos causados por fármacos incluem toxicidade aquática, desenvolvimento de resistência em bactérias patogênicas, genotoxicidade, e desregulação endócrina. Diferentes fontes podem ser indicadas para explicar o aparecimento de fármacos no ambiente aquático. Atualmente, é amplamente reconhecido que a principal fonte de poluição são os efluentes de ETE. Portanto, o descarte de resíduos farmacêuticos nos efluentes de ETE deve ser minimizado o máximo possível. A remoção de poluentes orgânicos recalcitrantes como fármacos na água e em efluentes pode ser obtida utilizando processos oxidativos avançados (POA). O objetivo deste trabalho é avaliar a eficiência de remoção de Propranolol por meio de POA, avaliar a toxicidade dos produtos de degradação durante os tratamentos bem como realizar um estudo cinético de degradação do composto. O fármaco usado neste estudo foi o Propranolol fornecido pelo LAFEPE. Foi utilizada solução modelo a 20 mgL-1 . Os tratamentos por meio de POA (H2O2/UV, Fenton e foto-Fenton) além de radiação UV (fotólise) e H2O2 foram realizados em escala laboratorial em um reator ao longo de 60 minutos. A radiação UV foi obtida por uma lâmpada a vapor de mercúrio de média pressão de 30 W. A agitação do sistema foi feita utilizando um agitador magnético. Sulfato ferroso heptahidratado foi utilizado como fonte de íons de ferro para o processo Fenton e foto-Fenton. A determinação e a quantificação do fármaco após tratamento por POA, foram realizadas em um espectrofotômetro UV-Vis. Em relação aos resultados obtidos pelo tratamento utilizando POA, o propranolol se mostrou pouco sensível a oxidação com peróxido de hidrogênio. O tratamento Foto-Fenton apresentou melhor eficiência de remoção e o Fenton o melhor resultado de toxicidade. A cinética de oxidação do fármaco foi discutida e verificou-se que o modelo cinético de pseudo-primeira ordem pode descrever melhor a oxidação do fármaco. As principais vantagens e desvantagens de cada processos e a complexidade de comparação dos vários processos de oxidação foram discutidos. O processo Foto-Fenton foi o que removeu mais de 80% do propranolol a 20 mg L-1 em 15 minutos.
The occurrence of pharmaceuticals in the environment has become a subject of interest in recent years. A vast number of these compounds have been detected in sewage treatment plant (STP) effluents, surface waters and, less frequently, in groundwater and drinking water, all over the world. Some of the adverse effects caused by pharmaceuticals include aquatic toxicity, resistance development in pathogenic bacteria, genotoxicity and endocrine disruption. Different sources can be indicated to explain the appearance of pharmaceuticals in the aquatic environment. Nowadays, it is widely accepted that the main source of pollution are STP effluents. Therefore, the discharge of pharmaceutical residues to the environment in STP effluents should be minimized. Removal of recalcitrant organic pollutants such as pharmaceuticals in water and wastewater can be achieved using advanced treatment technologies such as advanced oxidation processes (AOP). The objective of this study is to evaluate the removal efficiency of Propranolol by AOP to identify the degradation products toxicity as well as to perform a degradation kinetic study of these compounds. The pharmaceutical used in this study was Propranolol were purchased from LAFEPE. The pharmaceutical were spiked daily at a concentration of 20 mgL-1 were treated by AOP. The treatments by AOP (H2O2/UV, Fenton and photo-Fenton) and photolysis (UV radiation) and peroxide, were performed in a reactor along 60 minutes. UV radiation was provided by a medium pressure mercury lamp of 30 W. The agitation of the system was realized by a magnetic bar. Ferrous sulfate heptahydrate was used as source of iron for the Fenton and photo-Fenton process. The determination and quantification of the pharmaceutical present during the treatment by AOP were performed with UV-Vis spectrophotometer. With regard to the results obtained by using AOP treatment, the propranolol was less sensitive to hydrogen peroxide. Despite photo-fenton treatment presented the highest removal efficiency and Fenton the best treatment toxicity. The kinetics of oxidation of propranolol has been discussed and it was found that the pseudo-first order kinetic model can describe the oxidation. The main advantages and disadvantages of each process and the complexity of comparing the various advanced oxidation processes (AOP) was discussed. In the photo-fenton process it was possible to remove more than 80% from propranolol concentration of 20 mg L-1 in 15 minutes.
35
de, Caldeira Ricardo Luis Franco. "An assessment of cross-contamination issues in the context of chemical and pharmaceutical processes using a continuous oscillatory baffled reactor." Thesis, Heriot-Watt University, 2010. http://hdl.handle.net/10399/2381.
Full textAbstract:
Past research in oscillatory baffled reactors has shown that there are significant technological and business advantages in using such reactor technology in fine chemical and pharmaceutical industries: shorter reaction times, fewer by-products, uniform product quality and higher yields, while at the same time with a significant saving in space, capital and running costs. This project focused on the robustness and adaptability of the continuous oscillatory baffled reactor (COBR) for a large spectrum of chemical reactions that are performed in very different fields of industry: from cosmetics and fine chemicals to pharmaceutical products. In particular, the emphasis was on cross contamination issues which may occur when different reactions are performed in a tandem fashion in this reactor. The experimental results indicate that the COBR is well suited to a broad spectrum of chemical reactions, as well as for crystallization operations. During the continuous production of a fine chemical and two active pharmaceutical ingredients in tandem the conditions inside the reactor remained stable and were easily controlled. The minimal amounts of contaminants present and the high quality of the products obtained are a testament to the consistent operation and robust nature of the COBR. The three production phases were interspersed with a well-defined cleaning procedure. The established cleaning protocol is simple, efficient and fast, while the amount of waste generated is minimized. The cleaning kinetics is of first order, which is consistent with previous work. The results reported in this thesis show that the COBR, which incorporates quality-by-design principles, is a suitable alternative to current mixing technologies and can be readily assimilated into a variety of fine chemical and pharmaceutical manufacturing processes.
36
Perra, Simone. "The study of Lovastatin production as a benchmark simulation model for bio-manufacturing processes." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2020.
Find full textAbstract:
In this work an end to end bio-pharmaceutical process for the production of lovastatin is implemented into a Matlab/Simulink environment.
The simulation is developed with the objective to be a generic reference model, as it captures the typical dynamics of pharmaceutical bio-manufacturing. It can then be used as an open-source test problem to study different process scenarios in dynamic mode.
The objective of this work is to propose the benchmark simulation as a testbed for the development and comparison of different control strategies in dynamic mode. To this purpose a highly referenced control framework (the Skogestad method) is adapted and applied to the dynamics of the present model. The implemented framework includes a distributed control system (DCS) as regulatory control layer, and an MPC multiple-input multiple-output application as a supervisory control layer. As an alternative for the supervisory control layer, an override control framework based on process knowledge is developed and validated as a lighter solution. The different control setups are compared from a total productivity and stability point of view in a set of case-studies. As expected, the MPC application is the most stable solution, but in all the case studies the alternative override supervisory control gives comparable API final productivity. Pharmaceutical bio-manufacturing is a highly regulated industry in which the resources and time dedicated to process optimization and control are limited. The development of an end to end reference simulation with a limited number of unit operations is a step towards a smarter resource exploitation in the industry.
37
Günes, Ata, and Sarmiento Leonardo Arboleda. "What would middle managers do? A Case Study of a Culturally Shifting Global Pharmaceutical Company." Thesis, Jönköping University, Internationella Handelshögskolan, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-53064.
Full textAbstract:
Purpose The purpose of this paper is to explore how middle managers attempt to enhance internal innovation processes with digital usages. To do so, this research aims to open up an internal innovation process improvement ‘black box’ by looking not only at issues related to digital delivery but also at elements related to innovation culture and leadership. Design/method/approach To fulfill this purpose, this qualitative research develops a case study employing the lenses of middle managers to generate empirical data based on an interpretative approach and an in-depth semi-structured interview methodology. Findings Middle managers' attempt to enhance internal innovation processes with digital usages involves major elements related to influencing people’s mindset, motivating and embracing ideation, as well as collaboration across units leveraged by digital usages. Nonetheless, the core element of the attempt stands for the ability to root the digital tool usages not only at the individual or team level but also at the innovation process level. Contributions This study mainly contributes to theory extension by putting the individual at the heart of the organization's innovativeness culture and enlightening the leadership role of middle managers to influence innovative behaviors to embrace digital tools in the line of the organization’s strategy with major demands for change management. Originality/value By integrating the perspective of middle managers to the conceptual, this case study brings an additional piece to the puzzle of how digital tools nurture the internal innovation processes.
38
Salgado, Ricardo Manuel Nunes. "The removal of xenobiotic compounds from wastewater through the use of biological processes and advanced oxidation technologies." Doctoral thesis, Faculdade de Ciências e Tecnologia, 2011. http://hdl.handle.net/10362/6918.
Full textAbstract:
Dissertação apresentada para obtenção do Grau de Doutor em Engenharia Química e Bioquímica pela Universidade Nova de Lisboa, Faculdade de Ciências e TecnologiaFCT/MCTES projects PTDC/AMB/65702/2006 and SFRH/PROTEC/49449/2009 and SFRH/BPD/30800/2006 ; COST Action 636
39
Hancock, Bruno Caspar. "Material interactions and surface phenomena in size enlargement processes : an evaluation of the interactions occuring during the wet granulation of real and model pharmaceutical systems." Thesis, University of Bradford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262351.
Full text
40
Glisovic, Tina. "The Multifunctional HnRNP A1 Protein in the Regulation of the Cyp2a5 Gene : Connecting Transcriptional and Posttranscriptional Processes." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3412.
Full textAbstract:
The mouse xenobiotic-inducible Cyp2a5 gene is both transcriptionally and posttranscriptionally regulated. One of the most potent Cyp2a5 inducers, the hepatotoxin pyrazole, increases the CYP2A5 mRNA half-life. The induction is accomplished through the interaction of a pyrazole-inducible protein with a 71 nt long, putative hairpin-loop region in the 3' UTR of the CYP2A5 mRNA. The aims of this thesis have been to identify the pyrazole-inducible protein, to investigate its role in the Cyp2a5 expression and the significance of the 71 nt hairpin-loop region for the Cyp2a5 expression, and to examine a possible coupling between transcriptional and posttranscriptional processes in Cyp2a5 expression. The pyrazole-inducible protein was identified as the heterogeneous nuclear ribonucleoprotein (hnRNP) A1. Studies performed in mouse primary hepatocytes overexpressing hnRNP A1, and in mouse erythroleukemia derived cells lacking hnRNP A1, revealed that the 71 nt region in the 3' UTR of the CYP2A5 mRNA is essential for Cyp2a5 expression. The hnRNP A1 is a multifunctional nucleocytoplasmic shuttling protein, with the ability to bind both RNA and DNA. These properties make it an interesting candidate mediating a coupling between nuclear and cytoplasmic gene regulatory events, which was investigated for the Cyp2a5. In conditions of cellular stress hnRNP A1 translocates from the nucleus to the cytoplasm. The accumulation of cytoplasmic hnRNP A1 after RNA polymerase II transcription inhibition, resulted in an increased binding of hnRNP A1 to the CYP2A5 mRNA, parallel with a stabilization of the CYP2A5 mRNA. Treating primary mouse hepatocytes with phenobarbital (PB), a Cyp2a5 transcriptional inducer, resulted in a mainly nuclear localization of the hnRNP A1. Electrophoretic mobility shift assays with nuclear extracts from control or PB-treated mice, revealed that hnRNP A1 interacts with two regions in the Cyp2a5 proximal promoter, and that the interaction to one of the regions was stimulated by PB treatment. In conclusion, the change in hnRNP A1 subcellular localization after transcriptional inhibition or activation, together with the effects on the interaction of hnRNP A1 with the CYP2A5 mRNA and Cyp2a5 promoter, suggest that hnRNP A1 could couple the nuclear and cytoplasmic events of the Cyp2a5 expression. The presented studies are the first showing involvement of an hnRNP protein in the regulation of a Cyp gene. Moreover, it is the first time an interconnected transcriptional and posttranscriptional regulation has been suggested for a member of the Cyp gene family.
41
Le, Grevès Madeleine. "CNS Targets for GH and IGF-1 : Emphasis on Their Regulation in Relation to Cognitive Processes." Doctoral thesis, Uppsala University, Department of Pharmaceutical Biosciences, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4758.
Full textAbstract:
The interest for the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and its role in the central nervous system (CNS) has grown during the past decade. GH has been associated with psychological functions as sleep, mood, general well-being and learning and memory. The present thesis is a contribution to clarify the functions and mechanisms involved in the actions of GH and IGF-1 in the CNS. A variant of the GH receptor (GHR) gene transcript lacking exon 3 (GHR3-) was cloned from ovine choroid plexus epithelial cells and tissue. The GHR3- transcript has previously only been identified in human tissue. Further, an anatomical study of the localization of GHR mRNA in the rat brain stem and spinal cord was carried out by the use of in situ hybridization. High densities of GHRs were found in areas associated with the regulation of food intake, sleep and nociception, functions known to be influenced by the GH/IGF-1 axis. The interaction with the opioid system was studied by an acute treatment with morphine. The levels of the transcripts for GHR and GHBP in the rat hippocampus and spinal cord were decreased 4 h after the injection of the opiate and restored to normal levels after 24 h. Young and aged rats injected with GH or IGF-1 showed differential gene regulation of subunits of the NMDA subtype of glutamate receptor in the hippocampus. This indicates an age-related difference in the sensitivity to GH/IGF-1 mediated effects on memory functions. Moreover, hypophysectomized rats treated with GH showed improved performance in the Morris water maze, a spatial memory task. The effect was accompanied with an increase in transcripts for NMDA receptor subunits and its associated membrane anchoring PSD-95 protein. Taken together, the results suggest that GH and/or IGF-1 play important roles in mechanisms associated with cognitive functions.
42
Miró, Vera Aira Yira. "Development of analytical methods based on Near Infrared Spectroscopy for monitoring of pharmaceutical and biotechnological processes and control of new psychoactive substances." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/669569.
Full textAbstract:
L’espectroscòpia de l’infraroig proper (NIR per les seves sigles en anglès) és una tècnica analítica basada en la interacció de la radiació electromagnètica en el rang 780-2500 nm amb la matèria. L’espectre NIR es pot considerar una empremta única per cada substància o barreja d’aquestes, format per bandes resultants dels sobretons i combinacions de les vibracions fonamentals de la regió de l’infraroig mig. Addicionalment, en mostres sòlides, l’espectre NIR és sensible a la dispersió causada per les característiques físiques del producte, de manera que ofereix simultàniament informació de canvis físics i químics. L’aprofitament de la informació que contenen els espectres NIR implica l’aplicació de mètodes d’anàlisis multivariable. L’objectiu general d’aquesta tesis ha estat el desenvolupament de mètodes analítics basats en NIR pel seguiment de processos farmacèutics i biotecnològics, així com pel control de noves substàncies psicoactives (NPS per les seves sigles en anglès). Per a fer-ho, s’han explorat les següents condicions: i) extensió de rangs de concentració de principi actiu (API per les seves sigles en anglès) en l’aplicació de l’estratègia de l’espectre de procés (PS per les seves sigles en anglès) durant les etapes de granulació i compactació de preparats farmacèutics sòlids; ii) identificació de NPS utilitzant instruments portàtils i de laboratori, i iii) seguiment de la producció de Lipasa B recombinant de Candida antarctica en Pichia pastoris utilitzant glicerol com a font de carboni.La espectroscopía de infrarrojo cercano (NIR, por sus siglas en inglés) es una técnica analítica basada en la interacción entre la radiación electromagnética en el rango 780-2500 nm y la materia. El espectro NIR puede considerarse una huella única para cada sustancia o mezcla de ellas, compuesta por bandas resultantes de los sobretonos y combinaciones de las vibraciones fundamentales en la región del infrarrojo medio. Adicionalmente, en muestras sólidas, el espectro NIR es sensible a la dispersión causada por las características físicas de las muestras, de modo que ofrece simultáneamente información sobre cambios físicos y químicos. El aprovechamiento de la información contenida en espectros NIR implica la aplicación de métodos de análisis multivariable. El objetivo general de esta tesis ha sido el desarrollo de métodos analíticos basados en NIR para el seguimiento de procesos farmacéuticos y biotecnológicos, así como para el control de nuevas sustancias psicoactivas (NPS, por sus siglas en inglés). Para ello, se han explorado las siguientes condiciones: i) rangos extendidos de concentración de ingrediente activo (API, por sus siglas en inglés) en la aplicación de la estrategia del espectro de proceso (PS, por sus siglas en inglés) durante etapas de granulación y compactación de preparados sólidos farmacéuticos; ii) identificación de NPS utilizando instrumentos portátiles y de laboratorio, y iii) seguimiento de producción recombinante de Lipasa B de Candida antarctica en Pichia pastoris usando glicerol como fuente de carbono.
The Near Infrared Spectroscopy (NIRS) is an analytical technique based on the interaction of electromagnetic radiation in the wavelength range 780-2500 nm and matter. The NIR spectrum can be considered as a “fingerprint” of each chemical compound or mixture of them, which contains absorption bands that are the result of overtones and combinations of the fundamental vibrations observed in the Mid-Infrared region. Additionally, NIRS of solids is sensible to the scattering effect caused by physical characteristics of the samples, therefore provides simultaneous sensitivity to chemical and physical changes of solids. Because of NIR spectra show broad and overlapped bands makes it necessary the use of Chemometrics, which implies the application of statistical and mathematical methods to such spectral data, for achieving the maximal extraction and collection of useful information from it. The general objective of this doctoral thesis is developing analytical methods based on NIRS for monitoring pharmaceutical and biotechnological processes and for the control of illicit drugs. The following conditions have been considered i) extended active pharmaceutical ingredient (API) concentration ranges during granulation and tableting using the process spectrum (PS), ii) on-site identification of new psychoactive substances (NPS) during police seizing procedures with hand-held and bench-top instruments and iii) inline monitoring of the production of recombinant Lipase B from Candida antarctica in Pichia pastoris using Glycerol as carbon source. i) Extended API concentration ranges during granulation and tableting using the PS The PS is a methodology for preparing calibration sets by adding the changes due to the manufacturing process to NIR spectra of samples prepared at the laboratory, using an algebraic procedure. The PS has successfully included the process contributions during modelling in the central point of API concentration values of diverse formulations, however the properties of this methodology at extreme points of API concentration ranges have not been studied yet. For evaluating such properties, in this work the PS was applied to samples in the range of ± 30% of a nominal API value. Results have shown that the PS performance can be affected by API concentration changes in the studied range, and classical pre-treatments are not enough to overcome this condition. 4 ii) Comparison of the performance of bench-top and hand-held NIR instruments concerning the identification of NPS The NPS are 'legal highs' with molecular differences regarding the structures of illicit controlled drugs, whose emergence have expanded the current synthetic drugs market in a very important way. The feasibility of using portable NIRS instruments for the fast identification of NPS have been previously demonstrated, however, their performance has not been faced to the performance of bench-top instruments. Results presented in this thesis expose that, even when models developed using data from NIRS miniaturized instruments are limited in performance regarding those developed using data provided by bench-top instruments, classification models of NPS based on data from hand-held instruments can be useful to make real-time and on-site decisions that can be confirmed later using high performance analytical instrumentation. iii) Inline monitoring of the production of recombinant Lipase B from Candida antarctica in Pichia pastoris using glycerol as carbon source. The use of new constitutive promoters and recycled carbon sources in the recombinant production of industrial proteins, such as lipases, in the cell factory Pichia pastoris is advantageous for improving production yields and minimizing the cost of the culture medium. The capabilities of a NIR spectrometer with fiber optic coupling for immersion of a transflectance probe were employed for the inline monitoring of the cultivation mentioned in the headline. Quantitative models have been developed for Biomass, Total protein, Nitrogen and Activity, which have demonstrated better prediction capability during the feed batch stage than during the batch stage. Predictions of glycerol values has been probably affected by the formation of hydrogen bonds in the aqueos medium.
43
Arnroth, Cornelia. "A study of protein aggregation processes using Dynamic Light Scattering : Validation of the technique and experimental trial with an active pharmaceutical ingredient." Thesis, Uppsala universitet, Institutionen för cell- och molekylärbiologi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-422862.
Full textAbstract:
Protein pharmaceuticals is one of the fastest growing class of therapeutics today. However, they pose a lot of challenges in production lines due to their poor stability. Protein aggregation is one of the most common results of protein instability and is a risk factor regarding the quality of therapeutics. This master thesis at RISE focused on validating the techniques Dynamic Light Scattering (DLS) and multi angle DLS (MADLS) with respect to detection of aggregation. The model protein B-lactoglobulin was used to assess the robustness and accuracy of DLS. A comparison between two instruments from Malvern, Zetasizer Nano (2006) and Zetasizer Ultra (2018) was done with respect to DLS. It was determined that they were in many ways equivalent, but the newer model Ultra was favourable due to reduced noise and its ability to detect a lower concentration of aggregates. MADLS produced more precise results which is reflected in narrower distributions and has a higher sensitivity than DLS with regards to separating particles near in size. Both techniques proved sensitive enough to differentiate between aggregates and native protein. Experimental trials were performed with an active pharmaceutical ingredient, API. The experimental trials with the API aimed to investigate what conditions and surface-interfaces that might pose a risk for aggregation. Despite efforts put in creating an environment where aggregation could be monitored, aggregation could not be established. Measurements with the API generated less reliable results due to noisy data and a lack of reproducibility between individual measurements.
44
Hanna, Bishoy. "DEVELOPMENT AND VALIDATION OF A SEMI-PHYSIOLOGICAL PHARMACOKINETIC (PBPK) MODEL TO PREDICT SYSTEMIC AND PULMONARY EXPOSURES AFTER INTRAVENOUS, ORAL ADMINISTRATION AND PULMONARY INHALATION OF SELECTED DRUGS, BUDESONIDE, TOBRAMYCIN AND CIPROFLOXACIN, IN HUMANS." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5470.
Full textAbstract:
Using a semi-PBPK modeling/quantitative meta-analysis approach, this project investigated what factors affect pulmonary and systemic exposures of Budesonide (BUD), Tobramycin (TOB), and Ciprofloxacin (CIP) after inhalation:
Three structurally different pulmonary disposition models were developed for each drug, including pulmonary absorption (all three), excretion (TOB and CIP) and sequestration (TOB) in a peripheral and central lung compartment. Systemic disposition parameters were estimated using available human mean plasma (cp(t)) and sputum (cs(t)) concentration profiles after IV administration, and GI absorption parameters were estimated from these profiles after oral administration. Pulmonary disposition parameters were estimated from cp(t) and cs(t) profiles after inhalation using various devices along with their published pulmonary deposition characteristics. Appropriate covariate models accounted for effects of Cystic Fibrosis on the systemic disposition/GI absorption for TOB and CIP. Monte Carlo Simulations (MCS) were used to optimize parameters and validate the final models and parameter spaces against published data.
Despite limited available data, especially cs(t) for BUD and CIP (after IV administration), the point estimates for the final model parameters were mechanistically plausible for all three drugs and consistent with their known differences in physicochemical and ADME properties. Model predictions adequately described the observed cp(t) and cs(t) profiles as well as exposure metrics across studies.
As the most lipophilic drug, BUD showed the fastest pulmonary absorption rates and highest Fpul (83%). TOB, a very hydrophilic drug, exhibited (intracellular) pulmonary sequestration, resulting in slow pulmonary absorption and excretion and low Fpul (10%). CIP - as zwitterion - showed relatively slow pulmonary absorption and excretion, leading to low Fpul (8%); pulmonary excretion accounted for 27% of CIP overall elimination.
Results of a formal parameter sensitivity analysis demonstrated that, for all three drugs, after inhalation, (1) their systemic exposures (cp(t)) depend primarily on CLtot along with Fpul/sequestration combined with Foral; (2) increasing pulmonary exposures (cs(t)) can be accomplished by slowing down pulmonary absorption rates (kca) and/or slowing down mucociliary clearance from the lungs into the GI tract (kcm) – affirming the overall hypothesis guiding the project.
45
Rodgers, Ruth Mary. "Pharmaceutical ethics and professional discipline, 1993 to 1997 : an investigation into the Code of Ethics of the Royal Pharmaceutical Society of Great Britain : its implementation and influence on the disciplinary processes of the pharmacy profession dur." Thesis, Cardiff University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425998.
Full text
46
Ghashghaei, Ouldouz. "Development of New Multicomponent Processes based on Unexplored Chemistry of Isocyanides: Access to Heterocyclic Scaffolds and Applications." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/457764.
Full textAbstract:
1. It was observed that the interaction of imines and isocyanides in the presence of a Lewis acid can lead to a variety of scaffolds including α-aminoamides, α-aminoamidines, indoles and diiminoazetidines. The reaction conditions were optimized to yield the later as the main product. Screening the scope of amines, aldehydes and isocyanides led to a small library of azetidine adducts. Also, a few spiro-azetidine adducts were prepared using isatine ketimines. A unified mechanism was proposed to explain the structural diversity that the process offers. In case of the main azetidine adduct, the process goes through consecutive insertion of two isocyanides followed by a 4-exo-dig cyclization. The structural elucidation of the azetidine compounds confirms the unexpected syn nature of the formed imine bonds.
2. It was shown that N-insertion of isocyanides to N-substituted propargylamines in the presence of HCl yields 1,3,4,5-tetrasubstituted imidazoliums salts. As the propargylamines arise from A3 reactions, the scope of the process in terms of aldehydes, amines, alkynes, and isocyanides was studied. The described conditions do not apply for aliphatic amines as opposed to the Zhu reaction [1] who used a different activation method (dual metallic catalysis). However, mild reaction conditions allow the incorporation of tert-Bu isocyanide, avoiding undesired elimination, as in Zhu conditions. Furthermore, the A3 reaction was successfully combined with the new reaction to obtain the imidazolium salts in a one pot process. We also explored the properties of the MCR adducts: As a proof of concept, an adduct was used as an NHC ligand for to catalyze a standard Suzuki coupling. Interestingly, some of the obtained compounds displayed potent antiparasitic activity against Trypanosoma brucei and T. cruzi at nanomolar level.
3. A TMSCl- catalyzed Reissert type MCR was studied. The process features insertion of isocyanide to N-Si bond as the mechanistical key step. Computational and experimental methods were applied to study this novel interaction of isocyanides and N-Si bonds. The reaction yields aminoimidazolium salts from the incorporation of two isocyanide units into azines. The new activation mode offers significantly wider scope. Regioselective incorporation of two distinct isocyanides was successfully performed. Furthermore, some obtained adducts demonstrated potent antiparasitic properties against Trypanosoma Brucei and Cruzi.
[1] S. Tong, Q. Wang, M.-X. Wang, J. Zhu, Angew. Chem. Int. Ed. 2015, 54, 1293–1297.
The paper of Zhu group was published when the project was in the course of manuscript writing.
4. The application of multiple Groebcke-Bienaymé-Blackburn reactions on di- and triaminoazines leads to the formation of a variety of new N-fused heterocyclic scaffolds (aminoimidazopyridines) with several diversity points. The selective reactivity mode of diaminopyrimidine provides controlled synthesis of non-symmetrical adducts. The scope of reaction was studied (analyzing the range of the aldehyde, isocyanide and aminoazine components) and post- modifications were applied to further diversify the rich structural outcome of the process. Adducts arising from melamine were structurally enlarged, exploiting cross-coupling reactions to achieve nanosized tripodal structures. The synthesized adducts displayed interesting pH and environment sensitive fluorescent properties. Interestingly, a novel borylated BODYPY-type adduct was successfully synthesized and used for staining lysosomes in mammal cells Moreover, some adducts demonstrated potent antiviral activity against Adenovirus. Furthermore, selected compounds they showed selective affinity to G-quadruplex DNA sequences, suggesting potential applications in medicinal and biological chemistry.• La interacción de iminas e isocianuros en presencia de un ácido de Lewis puede conducir a una variedad de tipos estructurales incluyendo diiminoazetidinas. La selección del alcance de la reacción dio lugar a una pequeña biblioteca de aductos de azetidina. También, se prepararon unos pocos aductos de espiro-azetidina usando isatinas. Se propuso un mecanismo unificado para explicar la diversidad estructural que ofrece el proceso. • La inserción de isonitrilos en el enlace N-H de propargilaminas N-sustituidas en presencia de HCl proporcionó sales de imidazolio 1,3,4,5-tetrasustituidas. Como las propargilaminas proceden de reacciones de A3, se estudió el alcance del procedimiento en términos de aldehídos, aminas, alquinos e isocianuros. La reacción de A3 se combinó con la nueva reacción para obtener las sales de imidazolio en un proceso de una sola etapa. También se exploraron las propiedades de los aductos MCR: Como una prueba de concepto, un aducto se utilizó como un ligando NHC para catalizar un acoplamiento estándar de Suzuki. Algunos de los compuestos obtenidos mostraron una potente actividad antiparasitaria contra T. brucei y T. cruzi a nivel nanomolar. • Se estudió una MCR de tipo Reissert catalizada por TMSCl. El procedimiento presenta la inserción de isocianuro en enlace N-Si como paso clave. Se aplicaron métodos computacionales y experimentales para estudiar esta nueva interacción de isocianuros y enlaces N-Si. La reacción produce sales de aminoimidazolio a partir de la incorporación de dos isocianuros en azinas. El nuevo modo de activación ofrece un alcance mucho más amplio. Se realizó incorporación regioselectiva de dos isocianuros distintos. Algunos aductos demostraron potentes propiedades antiparasitarias contra Trypanosoma Brucei y Cruzi. • La aplicación de múltiples reacciones de GBB sobre poliaminoazinas dio lugar a la formación de nuevos tipos estructurales heterocíclicos N-fusionados con varios puntos de diversidad. El modo regioselectivo sobre diaminopirimidinas proporciona una síntesis controlada de aductos no simétricos. Se estudió el alcance de la reacción y se aplicaron modificaciones posteriores para diversificar aún más el resultado estructural del proceso. Los aductos de melamina se aumentaron de tamaño, explotando reacciones de acoplamiento cruzado para conseguir estructuras tridimensionales nanométricas. Los aductos sintetizados mostraron interesantes propiedades fluorescentes sensibles al pH y al medio ambiente. Se sintetizó un nuevo aducto de tipo BODYPY borilado y se usó para teñir lisosomas en células de mamífero. Además, algunos aductos demostraron una potente actividad antiviral contra Adenovirus humanos. Los compuestos seleccionados mostraron afinidad selectiva a las secuencias de ADN de G- quadruplex, lo que sugiere aplicaciones potenciales en química medicinal y biológica.
47
Ravipati, Dhatri. "Activity of Analogs of Anticancer Drugs on the Serine Protease Enzymes Subtilisin and Chymotrypsin." TopSCHOLAR®, 2011. http://digitalcommons.wku.edu/theses/1134.
Full textAbstract:
The anticancer activity of several platinum compounds is due to the formation of complexes with DNA. We hypothesize that the size and shape of the platinum compounds would impact interaction with proteins, and these interactions may be partly responsible for the anticancer activity. Chymotrypsin and subtilisin are serine proteases that have a histidine residue in the active site. We are investigating the inhibition of the digestive enzymes chymotrypsin and subtilisin by analogs of the anticancer drug cisplatin and trying to discern trends in the inhibition as the active site residues vary. In our research, we found that the enzyme subtilisin did not show any significant inhibition with different platinum compounds we used, while chymotrypsin showed inhibition only with the potassium tetrachloroplatinate and this inhibition is concentration dependent
48
Jarray, Ahmed. "Mesoscopic modeling, experimental and thermodynamic approach for the prediction of agglomerates structures in granulation processes." Phd thesis, Toulouse, INPT, 2015. http://oatao.univ-toulouse.fr/15112/1/jarray.pdf.
Full textAbstract:
Wet granulation process requires the addition of a coating agent or binder, typically composed of surfactants, water, plasticizers and fillers. In dry granulation however, the coating agent is added to the system in the form of fine solid particles. Our goals are to investigate the particles behaviour and agglomeration mechanism in dry and aqueous systems at the micro and meso scales, and also, to develop predictive methodologies and theoretical tools of investigation allowing to choose the adequate binder and to formulate the right coating solution. In this study we chose materials widely used in food and pharmaceutical industries, including; coating agents such as Hydroxypropyl-methylcellulose (HPMC) and Ethyl cellulose (EC), binders such as Polyvinylpyrrolidone (PVP) and Microcrystalline cellulose (MCC), hydrophobic filler such as Stearic acid (SA) and plasticizer such as Polyethylene glycol (PEG). A successful granulation requires good affinity between host and guest particles. In this context, in the first part of this work, two approaches to predict the binder-substrate affinity in dry and in aqueous media were compared; one based on the work of adhesion and the other based on the ideal tensile strength. The concept of ideal tensile strength was extended to ternary systems and applied for granulation in aqueous media. The developed approaches were thereafter tested for various systems (composed of PVP, MCC, HPMC, SA, EC, PEG and water) and compared to experimental observations. Approaches yielded results in good agreement with the experimental observations, but the work of adhesion approach might give more accurate affinity predictions on the particles affinity than the ideal tensile strength approach. Both approaches predicted that HPMC is a good binder for MCC. Results also indicated that PEG has a good affinity with HPMC and SA. In a second part of our work, we used mesoscale simulations and experimental techniques to investigate the structure of agglomerates formed in aqueous colloidal formulations used in coating and granulation processes. For the simulations, dissipative particle dynamics (DPD) and a coarse-grained approach were used. In the DPD method, the compounds were described as a set of soft beads interacting according to the Flory-Huggins model. The repulsive interactions between the beads were evaluated using the solubility parameter (δ) as input, where, δ was calculated by all-atom molecular simulations. The mesoscale simulation results were compared to experimental results obtained by Cryogenic-SEM, particle size distribution analysis and DSC technique. According to the DPD simulations, HPMC polymer is a better stabilizing agent for SA than PVP and MCC. In addition, HPMC is able to cover the SA particle with a thick layer ant to adsorb in depth into its inner core, preventing SA agglomeration and crystal growth. But, for high amounts of SA (above 10% (w/w)), HPMC is unable to fully stabilize SA. We also found that PEG polymer diffuses inside HPMC chains thereby extending and softening the composite polymer. Experimental results presented similar trends; particle size distribution analysis showed that in the presence of HPMC, for low percentages of SA (below 10% (w/w)), the majority of SA particles are below 1 μm in diameter. SEM images revealed that HPMC surrounds SA crystals with a hatching textured film and anchors on their surface.
49
Junior, Michel Bichara Jemael. "Peletização : estudo de processos de incorporação de princípios ativos em péletes inertes." Universidade de Taubaté, 2011. http://www.bdtd.unitau.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=261.
Full textAbstract:
O segmento farmacêutico demonstra um crescente interesse no processo de peletização, o qual consiste na aglomeração por via úmida de pós finos compostos de ativos e excipientes em pequenas unidades esféricas, com excelentes vantagens tecnológicas e terapêuticas. O objetivo do presente trabalho envolve o estudo de processos de incorporação de suspensões em péletes inertes, compostas de ativos e excipientes, utilizando dois tipos de processos: 1. Drageadeira Modificada e 2. Leito Fluidizado nas configurações top spray e bottom spray. Os ativos utilizados foram besilato de anlodipino nas concentrações de 2.5% e 5% em massa, e cloridrato de benazepril em 15% em massa, presentes nas formulações das suspensões e aplicadas em quantidades iguais nos dois processos, em um total de 9 lotes. Os indicadores de desempenho de processo utilizados para incorporação do ativo nos péletes inertes foram tempo de aplicação da suspensão (min) e taxa de aplicação da suspensão (g/min). Os péletes finais obtidos foram avaliados por meio das análises das propriedades físico-químicas: teor de umidade (%), teor de princípio ativo (%), uniformidade de conteúdo (%) e dissolução (%). Dentre os lotes testados, os processos em drageadeira e leito pelo sistema bottom spray apresentaram o menor tempo de aplicação (120 min) para a suspensão com o ativo anlodipino na concentração de 2.5%, enquanto que pelo sistema top spray apresentou um tempo de aplicação de 300 min, uma vez que este sistema foi projetado originalmente para processo de granulação. O processo em drageadeira apresentou a maior taxa real de aplicação, igual a 6.24 g/min, seguida pelo sistema bottom spray com 4.91 g/min, e o sistema top spray com 1.62 g/min, para suspensão com o ativo benazepril na concentração de 15%. Para os processos em drageadeira e leito pelo sistema bottom spray, todas as propriedades físico-químicas dos péletes deste estudo se apresentaram dentro dos padrões recomendados pela indústria farmacêutica, o que não aconteceu para o sistema top spray com relação à propriedade teor de princípio ativo (benazepril), cujo valor apresentado ficou em 12.90%, abaixo do limite inferior de 13.50%; o que não garantirá a eficácia do fármaco de acordo com a ação esperada. Os resultados apresentados ratificam os processos de peletização em drageadeira e leito pelo sistema bottom spray como os ideais pela técnica de incorporação de princípio ativo em péletes inertes.The pharmaceutical industry has shown a growing interest in pelletization process, which consists of wet agglomeration of fine powders composed of active ingredients and excipients into small spherical unities, with excellent technological and therapeutic advantages. The objective of this work involves the study of processes of incorporation of suspensions in inert pellets, composed of active ingredients and excipients, using two types of processes: 1. Modified Coating Pan and 2. Fluid Bed in top spray and bottom spray systems. The active ingredients used were amlodipine besylate in concentrations of 2.5% and 5% by mass, and benazepril hydrochloride 15% by mass, included in the formulations of suspensions and applied in equal amounts in both processes, in a total of 9 batches. The process performance indicators used for incorporation of the active ingredient in inert pellets were time of application of the suspension (min) and rate of application of the suspension (g/min). The final pellets were evaluated by means of analyses of the physicochemical properties: water content (%), assay of active ingredient (%), uniformity content (%) and dissolution (%). Among the batches tested, the processes in coating pan and fluid bed by bottom spray system had the shortest application time (120 min) for the suspension with amlodipine besylate active with concentration of 2.5%, while the top spray system had an application time of 300 min, since this system was originally designed for granulation process. The process in coating pan showed the highest real rate of application, equal to 6.24 g/min, followed by the bottom spray system with 4.91 g/min, and the top spray system with 1.62 g/min to the suspension with benazepril hydrochloride with concentration of 15%. For the processes in coating pan and fluid bed by the bottom spray system, all physicochemical properties of the pellets of this study are presented within the standards recommended by the pharmaceutical industry, which has not happened for the top spray system with respect to property "assay of active ingredient (benazepril), whose value present was in 12.90%, below the lower limit of 13.50%, which does not guarantee the efficacy of the drug according to the expected action. The results presented confirm the processes of pelletization in coating pan and fluid bed by the bottom spray system as the ideal technique for incorporation of the active ingredient in inert pellets.
50
Souza, Fernanda Siqueira. "Degradação de poluentes emergentes por processos oxidativos avançados (O3, O3/UV, O3/Fe2+, O3/UV/Fe2+) visando o tratamento de efluentes hospitalares." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/150518.
Full textAbstract:
Compostos farmacêuticos são detectados em diversas matrizes ambientais. Estes compostos, quando não eliminados por técnicas avançadas de tratamento, contribuem para impactos ambientais negativos. Especificamente, efluentes hospitalares apresentam altas concentrações destes compostos principalmente pela excreção por pacientes. Neste contexto, o presente trabalho visa contribuir com a pesquisa científica em relação a efluentes hospitalares no Brasil, propondo alternativas de tratamento com ozônio para a remoção de fármacos. Para atingir o objetivo proposto, foi realizado um diagnóstico em um hospital visando identificar o consumo das principais classes farmacêuticas. A partir deste estudo, desenvolveu-se um planejamento de experimentos para avaliar os parâmetros mais adequados do processo de ozonização para a remoção de cafeína (CAF), amoxicilina (AMX) e ampicilina (AMP) em soluções aquosas. Foram avaliados experimentalmente os processos O3, O3/UV, O3/Fe2+, O3/UV/Fe2+. Investigou-se a influência da concentração inicial de fármaco, do pH, da potência de luz UV aplicada e da concentração inicial de Fe2+ utilizado como catalisador homogêneo. A variável de resposta foi a eficiência de mineralização. Os parâmetros obtidos pelo planejamento experimental foram aplicados para o Atenolol (ATE) e para soluções aquosas contendo a mistura de todos os compostos analisados (CAF, AMX, AMP e ATE). Um estudo cinético para determinação das constantes de reação foi realizado para a cafeína e atenolol. Para avaliar o tratamento com efluente hospitalar, uma caracterização (detecção de compostos farmacêuticos e parâmetros físico-químicos e toxicológicos) foi realizada antes e após o processo que apresentou a melhor eficiência de mineralização. Com o objetivo de extrapolar os estudos realizados e avaliar outros poluentes emergentes, além dos compostos farmacêuticos, realizaram-se experimentos com 90 compostos como drogas de abuso, hormônios e produtos de higiene pessoal que também podem estar presentes em efluentes hospitalares, avaliando a influência do pH e da dosagem de ozônio aplicada. Como principais resultados, os antibióticos e cardiovasculares foram as classes farmacêuticas mais consumidas no hospital. Pelo planejamento de experimentos, observou-se que todos os compostos avaliados foram rapidamente degradados (100% em menos de 15min) e as melhores eficiências de mineralização atingiram 70,8%, 60,4% e 63,6% para CAF, AMX e AMP, respectivamente. O sistema O3/UV/Fe2+ obteve a melhor eficiência de mineralização para o ATE (67,9%) e para a mistura dos compostos (69,5%). O estudo cinético possibilitou o cálculo das constantes cinéticas: kO3 =697,46 M-1 s-1 e kOH = 6,41x109 M-1 s-1 para a cafeína; e kO3 =146,56 M-1 s-1 e kOH = 15,29x109 M-1 s-1 para o atenolol. A eficiência de mineralização para os experimentos com efluente hospitalar atingiu 54,7% para o sistema O3/UV, sendo eficiente para a completa eliminação de diversos compostos farmacêuticos e remoção da toxicidade. Em relação à remoção dos 90 poluentes emergentes, observou-se que 53,3% dos compostos foram completamente degradados utilizando uma razão mMO3/mMC=0,3 em pH neutro. Os resultados encontrados indicam que o presente trabalho contribui para o avanço da pesquisa sobre efluentes hospitalares, pois apresenta uma alternativa de tratamento eficiente para a completa remoção de diversos compostos farmacêuticos, minimizando o impacto negativo destes no meio ambiente.Pharmaceutical compounds (PhCs) are detected in various environmental matrices. These compounds, whether not eliminated by advanced treatment techniques, contribute to bacterial resistance and negative environmental impacts on water resource. Specifically, hospital wastewaster exhibit high concentrations of these compounds mainly by the excretion by patients. In this context, this paper aims to contribute to scientific research regarding hospital wastewater in Brazil, proposing treatment alternatives by ozone to remove PhCs. To achieve this purpose, it conducted a diagnosis in a hospital to identify the consumption of major pharmaceutical classes. With this result, it developed an experimental design to evaluate the most appropriate parameters of the ozonation process for the removal of caffeine (CAF), amoxicillin (AMX) and ampicillin (AMP) in aqueous solutions. This study evaluated the following processes experimentally: O3, O3/UV, O3/Fe2+ O3/UV/Fe2+. The influence of ozone dose, initial PhCs concentration, pH, power UV light applied and Fe2+ initial concentration used as homogeneous catalyst were investigated. Mineralization efficiency was the response variable. Parameters obtained by the experimental design were applied for Atenolol (ATE) and aqueous solutions containing the mixture of all compounds analyzed (CAF, AMX, AMP and ATE). A kinetic study for the determination of reaction constants was carried out for caffeine and atenolol. To evaluate the hospital wastewater treatment, a characterization (detection of pharmaceutical compounds and physico-chemical and toxicological parameters) was performed before and after the process that showed the best mineralization efficiency. In order to extrapolate the studies and evaluate other emergent pollutants, in addition to pharmaceutical compounds, were conducted experiments with 90 compounds such as illicit drugs, hormones and personal care products, which also may be present in hospital wastewater, evaluating the influence of pH and ozone dosage. Main results showed that antibiotics and cardiovascular were the most consumed pharmaceutical classes in the hospital. For the design of experiments, it was observed that all the evaluated compounds were rapidly degraded (100% in less than 15 minutes) and the best mineralization efficiency reached 70.8%, 60.4% and 63.6% for CAF and AMX AMP, respectively. The system O3/UV/Fe2+ obtained the best mineralization efficiency for ATE (67.9%) and mixture of compounds (69.5%). The kinetic study allowed the determination of the kinetic constants: kO3 = 697.46 M-1 s-1 and kOH = 6.41x109 M-1 s-1 for caffeine; and kO3 = 146.56 M-1 s-1 and kOH = 15.29x109 M-1 s-1 for atenolol. Mineralization efficiency for hospital wastewater experiments reached 54.7% by the system O3/UV, being efficient for complete elimination of various PhCs and removal of toxicity. Regarding the removal of 90 emergent pollutants, it was observed that 53.3% of the compounds were completely degraded using a ratio mMO3/MMC = 0.3 at neutral pH. The results indicated that this work contributes to the advance of research on hospital wastewater, because it presents an effective alternative treatment for complete removal of various pharmaceutical compounds, minimizing the negative impact on the environment.