Spatially and angularly resolved diffuse reflectance measurement for in-line analysis of particle suspensions, a multi-sensor approach

  • Carla Sofia Ferreira

Student thesis: Doctoral Thesis


Particle size and shape are critical quality attributes for active pharmaceutical ingredients (API) as they have direct impact on downstream processing, as well as on the performance behaviour of the finished product. None of the current process analytical technologies (PAT), although capable of providing an indication on these key attributes, measures particle size directly. Obtaining a reliable and robust quantitative information of these particle attributes in real-time remains a great challenge across the multiple manufacturing steps and cannot be achieved by just using a single sensor. A Spatially and Angularly-Resolved Diffuse Reflectance Measurement (SAR-DRM) technology is for the first time applied to monitor micron size particles. SAR-DRM relies on multiple scattering of particles and collects multi-wavelength (UV-visibleNIR) diffuse reflectance spectra from optical fibres of multi-angle multi-space arrangements. Each SAR-DRM spectrum yields differences which correspond to the light travelling differently in the sample and to being differently affected by scattering and absorption effects. This technique is used alongside with Focus Beam Reflectance Measurement (FBRM) and Particle Vision and Measurement (PVM) which have been widely applied for in-line monitoring of particle attributes in crystallisation processes, in order to examine the SAR-DRM performance and investigate the possibility to broadening the size and concentration ranges of the applications.;The investigation was carried out on two model systems: polystyrene beads suspensions in water and alpha lactose monohydrate suspensions in acetone, for size (
Date of Award4 Jun 2020
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorYi-Chieh Chen (Supervisor) & Jan Sefcik (Supervisor)

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