Thesis

Process analytical technologies for particle characterisation and solid form analysis in continuous secondary pharmaceutical manufacturing

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Awarding institution
  • University of Strathclyde
Date of award
  • 2023
Thesis identifier
  • T16647
Person Identifier (Local)
  • 201363095
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • A placebo formulation of granules produced during continuous twin screw granulation were studied on-line using a new dynamic image particle size analyser. A DoE approach was carried out in order to evaluate the image analysers ability to study granules produced in a way that represented a continuous manufacturing environment, something not yet reported in the literature. This study proved to be challenging due to fouling issues, however once these were addressed and eliminated, the process analysis technology (PAT) proved to be a useful tool for real time analysis of granules. A low frequency Raman spectrometer (LFRS), was introduced to in-line and off-line analysis of amorphous solid dispersions (ASD) produced by hot melt extrusion (HME). The study looked at the solubility of Affinisol and paracetamol in polymer matrices directly during HME. Structural phase transitions were observed during HME processes and were successful in determining crystalline and amorphous material in-line and real time. Stability and homogeneity studies of varying concentrations of PCMAFF ASDs were studied. PCA was used to compare and validate LFRS to XRPD analysis. LFR results were also compared to DSC and Raman Spectroscopy. ASD’s with high concentrations of ASD were more unstable showing crystallisation over time. LFRS proved to be a good alternative to DSC and XRPD for solid state analysis. LFR was then applied to resolve a HME industrial issue. Different solid forms of Slaframine (SMZ) were produced using milling, cryo-milling, bulk material of Form II SMZ was then produced by crystallisation of FI to FII. The different solid states were then analysed using LFR. Classical least squares regression analysis was applied to mixtures of Form I, Form II and the Amorphous form of Sulfamerazine to look at the phase changes with time. LFRS studies determine the presence of unstable amorphous material produced during cryo-milling, something that XRPD was unable to do due to long analysis times and the amorphous SMZ instability.
Advisor / supervisor
  • Nordon, Alison
Resource Type
DOI
Date Created
  • 2022

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