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dc.contributor.advisorGerogiorgis, Dimitrios
dc.contributor.advisorFriedrich, Daniel
dc.contributor.authorJolliffe, Hikaru Graeme
dc.date.accessioned2019-03-15T16:41:17Z
dc.date.available2019-03-15T16:41:17Z
dc.date.issued2018-07-04
dc.identifier.urihttp://hdl.handle.net/1842/35579
dc.description.abstractContinuous Pharmaceutical Manufacturing (CPM) is a recent field of research that shows promise towards overcoming some of the technical and economic difficulties faced by a batch-production-dominated pharmaceutical sector. This PhD Thesis explores potential benefits of CPM by bringing together and comprehensively studying kinetic data analysis, process modelling and simulation, and technoeconomic evaluation via nonlinear optimisation. The CPM of two Active Pharmaceutical Ingredients (APIs) are studied in this Thesis: ibuprofen (a widely used over-the-counter analgaesic) and artemisinin (a key antimalarial substance). The continuous synthesis routes of these APIs have been published in the literature, and the kinetic data is analysed to allow the creation of process models. These are simulated with the aid of a variety of software packages (Excel, MATLAB). Continuous separation technologies, key to realising the full potential of CPM, are also studied. These include continuous liquid-liquid-extraction (LLE) operations and continuous crystallisation. Published performance data for these operations allows continuous API recovery to be simulated. Where necessary, solubility estimation methods (UNIFAC, NRTL) are employed for APIs in single, binary and ternary solutions. Established cost estimation methods are used to evaluate the economic merit of the processes and process options. These include capacity-cost correlations, cost factors to account for equipment design options, and widely used, reliable assumptions for a working plant. Material and equipment prices are drawn from a wide range of sources. The technical and economic aspects of the work are also brought together in nonlinear optimisation formulations to comprehensively explore the design spaces and determine optimal total costs. The MATLAB software package with the OPTI Toolbox plugin is used, which allows the use of a great variety of nonlinear optimisation algorithms, including both local and global solvers, and those for derivative-free optimisation. The CPM models are given multiple decision variables (such as cooling temperature, quantity of antisolvent use, number of separation unit operations) and are optimised for minimum total cost. The work in this PhD represents the first time that open-source kinetic and economic data is combined with explicit thermodynamic property modelling in a nonlinear optimisation framework to determine optimum design solutions, toward showing firstly how CPM can be beneficial and secondly how Process Systems Engineering and optimisation tools can be used in this regard. The use of systematic frameworks and design methods will be of paramount importance in continuing to build the case for CPM.en
dc.contributor.sponsorEngineering and Physical Sciences Research Council (EPSRC)en
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.relation.hasversionPlantwide technoeconomic analysis and separation solvent selection for continuous pharmaceutical manufacturing: Ibuprofen, artemisinin, and diphenhydramine Diab, S., Jolliffe, H. & Gerogiorgis, D. 10 Mar 2018 Computer Aided Chemical Engineering. Elsevier B.V., Vol. 41, p. 85-120 36 p.en
dc.relation.hasversionPlantwide design and economic evaluation of two Continuous Pharmaceutical Manufacturing (CPM) Cases: ibuprofen and artemisinin Jolliffe, H. G. & Gerogiorgis, D. 1 Aug 2016 In : Computers and Chemical Engineering.en
dc.relation.hasversionNonlinear optimisation via explicit NRTL model solubility prediction for antisolvent mixture selection in artemisinin crystallisation Jolliffe, H., Diab, S. & Gerogiorgis, D. 28 Nov 2017 In : Organic Process Research & Development.en
dc.relation.hasversionTechnoeconomic Optimization of a Conceptual Flowsheet for Continuous Separation of an Analgaesic Active Pharmaceutical Ingredient (API) Jolliffe, H. G. & Gerogiorgis, D. I. 19 Apr 2017 In : Industrial and Engineering Chemistry Research. 56, 15, p. 4357-4376 20 p.en
dc.relation.hasversionProcess modelling and simulation for continuous pharmaceutical manufacturing of artemisinin Jolliffe, H. G. & Gerogiorgis, D. 1 Aug 2016 In : Chemical Engineering Research and Design.en
dc.relation.hasversionPlantwide design and economic evaluation of two Continuous Pharmaceutical Manufacturing (CPM) cases: Ibuprofen and Artemisinin Jolliffe, H. G. & Gerogiorgis, D. 2015 12th International Symposium on Process Systems Engineering and 25th European Symposium on Computer Aided Process Engineering. Gernaey, K. V., Huusom, J. K. & Gani, R. (eds.). AMSTERDAM: Elsevier B.V., Vol. 9780444634290, p. 2213-2218 6 p. (Computer-Aided Chemical Engineering)en
dc.relation.hasversionContinuous pharmaceutical process engineering and economics: Investigating technical efficiency, environmental impact and economic viability Gerogiorgis, D. & Jolliffe, H. G. 30 Dec 2015 In : Chemistry Today. 33, 6, p. 29-32 4 p.en
dc.relation.hasversionProcess modelling and simulation for continuous pharmaceutical manufacturing of ibuprofen Jolliffe, H. G. & Gerogiorgis, D. 1 May 2015 In : Chemical Engineering Research and Design. 97, p. 175-191en
dc.subjectContinuous Pharmaceutical Manufacturingen
dc.subjectkinetic data analysisen
dc.subjectprocess modellingen
dc.subjecttechnoeconomic evaluationen
dc.subjectcontinuous separation technologiesen
dc.subjectcost factorsen
dc.titleContinuous pharmaceutical manufacturing (CPM): process modelling and economic optimisationen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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