Process intensification through electric field enhanced crystallisation and particle separation

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2020
Thesis identifier
  • T15813
Person Identifier (Local)
  • 201672247
Qualification Level
Qualification Name
Department, School or Faculty
  • Crystallisation is a fundamental unit operation in purification and separation process. It has been amply adopted in the pharmaceutical and fine chemical industry as a product of high purity can be obtained in a particulate solid form. This unit operation allows for tailoring product characteristics, providing extensive benefits to industries that operate in highly regulated environments. In particular, the pharmaceutical industry must abide with a complex set of regulations and laws imposed on drug products intended to protect the health of the public. Thus, in order to gain a competitive edge, pharmaceutical industries invest significant time and resources to optimize the manufacturing process. In this context, increasing research is focused on the optimization of crystallisation. One of the major issues that may occur during the purification process is the concomitant crystallisation of other substances together with the Active Pharmaceutical Ingredient (API), which may reduce the purity of the product below the compliance level. This thesis explores the effects of an externally applied electric field on suspended crystals and on crystallisation, aiming at the understanding of the fundamental principles of the interaction of the electric field with suspensions of particles and solutions of small organic molecules such as pharmaceutical compounds. Then, electric fields can be exploited as a process intensification tool to aid purification processes. For instance, rather than alleviating a concomitant crystallisation problem, the use of an externally applied field could make use of a concomitantly crystallising system to purify and separate two crystalline products in a single process step. The manipulation of suspended particles driven by electric field requires elevated electric fields which might result in the generation of electric current into the fluid system, inducing undesired chemical reactions that may affect the final product. To minimize electric current, non-polar solvents constitute of small molecules such as dioxane can be used. In Chapter 3, the solution behaviour of a number of APIs in non-polar solvents are studied in order to define suitable systems that resist electrolysis under strong electric fields, and therefore allow for the design of crystallisation processes under such conditions. From a number of thermodynamic models, the van ’t Hoff equations presented good correlation values to the experimental data, and therefore it can be used to extrapolate and interpolate solubility data at any given temperature. In addition, solution behaviour was studied from determined activity coefficients, which showed that all the studied systems positively or negative ly deviated from ideality. The Wilson activity coefficient model was used to predict these deviations. From well-defined systems, particle and solution properties can then be related to the electric field phenomena, leading to the identification of the scientific principles behind the interactions between the particles and the electric field. Suspensions of APIs of small organic molecules in different apolar solvent were studied under the presence of non-uniform and uniform electric fields in Chapter 4, which enabled to assess the electrokinetic phenomena associated to the motion of the suspended crystalline particles. Under an electric field, suspended particles travelled to and accumulated on a particular electrode. The greater dielectric properties of the organic compounds compared to that of the apolar solvents induce s a motion of particles towards an electrode by positive dielectrophoresis. The collection of particles on an electrode of a particular charge is due to electrophoretic forces acting on the surface charge of the particle. The collection on a specific electrode was anticipated by the sign of the zeta-potential of the solid phase. Other phenomena such as electro-osmosis and electrorheological fluids were observed in the studied systems in the presence of a strong electric field. The investigation of equilibrated suspensions in an electric field raises the question of the effects of the energy input in metastable systems. Chapter 5 explores the effect of strong electric fields in crystallisation processes of solutions of a small organic compound (isonicotinamide) in a non-polar solvent (dioxane). An electric field directly applied to a supersaturated solution of isonicotinamide in 1,4-dioxane enhances the nucleation kinetics of the small organic molecules. Thus, in the presence of an electric field, nucleation occurs at higher temperatures and shorter induction times for a given solution composition compared to crystallisation processes in the absence of an externally applied field. A plausible explanation is the accumulation of monomers of the crystalline compound in the vicinity of the electrodes due to electrokinetic forces. This phenomenon could increase the local supersaturation, resulting in an effective increase of the frequency of successful attachment of building units. Then, the combined action of the electric field effects on suspended particles and crystallisation from solution can be applied to developing means to exploit the electric field phenomena for the separation of heterogeneous suspensions. In Chapter 6, a number of multicomponent mixtures have been successfully separated in-situ by the use of inhomogeneous electric fields. The separation of two crystallising compounds that collect on opposite electrodes under the electric field was achieved with high purity values by cooling crystallisation in the presence of the field. In addition, the separation of compounds that collect on counter electrodes was carried out by a two-step seeding/cooling crystallisation method driven by electric fields. Thus, the separation method can potential be implemented as a tool to aid separation and purification processes. This thesis investigated the scientific principles behind the interaction of the electric field with both particle suspensions and crystallising solutions. By relating particle and solution properties to the observed phenomena, we were able to anticipate the behaviour of particles and solutions in an electric field, and then exploit the phenomena to separate complex mixtures of two crystallising compounds in situ. The gained knowledge can be applied as an intensification tool to aid purification and separation processes.
Advisor / supervisor
  • Roy, Sudipta.
  • Ter Horst, Joop H.
Resource Type
  • Strathclyde theses - ask staff. Thesis no. : T15813
  • Previously held under moratorium from 18th February 2020 until 18th February 2023
Date Created
  • 2020
Former identifier
  • 9912955092502996