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peer-reviewed Solution crystallization processes are widely treated as binary systems consisting of a solute and a solvent. For real systems, additional components such as additives and impurities may significantly impact crystallization processes even when present in very small amounts. An understanding of the mechanistic role of additives and impurities is therefore essential to design and control crystallization processes. This thesis first describes the solubility and crystallization of pure active pharmaceutical ingredients (API’s) from solution. Subsequently, it discusses the thermodynamic, kinetic and crystallization effects, caused by impurities. Eventually, these knowledge were applied to optimize impurity removal processes by using a combined experimental-modelling approach to investigate a mother-liquor recycle operation and improve properties on the processability of API. The gravimetric solubility method and how solubility models cope with industrially-relevant complex products belonging to the α-Thio-β-chloroacrylamide family which is a class of highly versatile synthetic intermediates was examined. One of the drawbacks of the gravimetric method is the evaporation of solvents which is due to elevated operating temperature or the volatile nature of the solvent itself. Solubility data at higher temperatures, beyond the atmospheric boiling point of solvents, allows for an increase in crystallization yield. A pressurized-synthetic methodology was presented as a new technique for determining high-temperature solubility data even beyond the atmospheric boiling point. With the gravimetric method in combination with HPLC analysis, the effect of impurities (4-nitrophenol and 4’-chloroacetanilide) on the solubility of paracetamol has been determined and modelled. To study the effect of volume on the nucleation kinetics of paracetamol, an automated FBRM-method was applied to record induction times. The shear rate was rationalized to be the part of the kinetic parameter that changes most significantly when changing the crystallizer type, up to a specific volume beyond which the effect becomes negligible. Induction time experiments were used in combination with the classical nucleation theory and demonstrated that the impurities employed reduced the nucleation rate. The impurities did not affect the solid−liquid interfacial energy but significantly reduced the kinetic factor. The poor compression ability of paracetamol is well known. The crystal habit of paracetamol was altered in the present of structurally similar impurity (4’-chloroacetanilide) to improve the compaction behaviour of the paracetamol crystals. An experimental design space was developed and utilized to select the most important process parameters for impurity incorporation. As a result, it was feasible to accurately control the compressibility and the amount of 4’-chloroacetanilide in the solid phase of paracetamol by simply choosing the required alcohol as the solvent for crystallization. In crystallization process, recycle of mother liquor allows for reduced waste and increased yield with complete control of the impurity concentration. A sequence of batch-cooling crystallization experiments was demonstrated to investigate how a mother liquor recycle operation affects the crystallization of paracetamol as a result of the gradual build-up of the impurity 4-nitrophenol. The results can be used as a guide to estimate the optimum mother liquor recycle conditions that would lead to reduced product and solvent waste and improved process efficiency. The result of this thesis addresses a number of challenges in the crystallization of API’s and impurities and leads to improved impurity removal processes. To obtain high yield as well as specific crystal quality attributes while maintaining a control on impurities, techniques strategies including continuous crystallization with recycle and pressurized methods were developed. Furthermore, rational process control over the incorporation of impurities and additives allows for advanced manufacturing of products with tailored specifications.

Understanding the behavior of a mooring line that is connected to a Suezmax vessel is a crucial requirement for our industry. Thus, we should model and analyze such a mooring line under a variety of environmental conditions. The output of modeling and analysis are useful to determine if the given mooring line is suitable for that environment or not. In the first part of this project a brief description about floating production platforms and mooring systems has been given and different material used for mooring systems has been discussed. All loads acts on mooring systems have been described and design methods used for mooring system analyses with relevant equation have been summarized. Brief descriptions about standards and guidelines used for mooring analysis have been given. Since we will use RIFLEX software for mooring line analysis, a brief introduction about the concept of the software will be provided. A single mooring line is studied that consists of two material compositions and is connected to Suezmax vessel. In the last part of this thesis, static and dynamic analysis in two regular wave cases will be performed for given mooring lines. We will do the analyses under three tensions 15%, 30% and 45% MBL (Minimum Breaking Load) in two vessel conditions (i.e. ballasted and loaded). The main focus is on effective tension and line displacement determination, that a given mooring line experiences. The results have been discussed.