Thesis

Spatially resolved spectroscopy for monitoring the solvent content in pharmaceutical drying

Downloadable Content

Download PDF
Creator
Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2024
Thesis identifier
  • T17081
Person Identifier (Local)
  • 202093993
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • The pharmaceutical drying process is critical to the quality of the active pharmaceutical ingredient or the drug product as it is often the final unit operation. The non-uniformity of drying is particularly challenging as it renders inaccurate the determined solvent content and drying endpoint, which is a critical quality attribute. As process analytical technology further develops, novel techniques are implemented to address process and product challenges. Spatially resolved spectroscopy is a technique in which spectra are collected from spatially resolved distances from the incident light. This technique is used for the characterisation of non-uniform media. In this thesis, the use of spatially resolved spectroscopy for the monitoring of the drying of an active pharmaceutical ingredient is reported. Pharmaceutical drying of model systems was monitored using spatially resolved spectroscopy. In this work, three bespoke probes were used for the collection of spatially resolved spectra. One probe allows the collection of spatially and angularly resolved diffuse reflectance near-infrared measurements (SAR-DRM), while the other was developed for the collection of spatially offset Raman spectroscopy (SORS) measurements. The third probe combines both techniques and was developed for the collection of both spatially resolved near-infrared spectra and spatially offset Raman spectra and is termed the combined probe. This thesis details the in-line and at-line application for industrial process monitoring using these techniques, which to our knowledge were not applied in this setting. The drying of two grades of paracetamol, granular and powder, in the solvents n-heptane and methyl tert-butyl ether was monitored using SAR-DRM. The drying of granular and powder paracetamol in the solvents anisole and methyl tert-butyl ether was monitored using SORS. Partial least squares regression (PLSR) analysis was used for the estimation of the solvent content using spectra from the individual signal collection configurations, in addition to a combination of the configurations. Results from both techniques suggest that PLSR models of spectra collected from larger distances lead to more accurate vii estimations of the solvent content. This was attributed to the larger volume of the drying powder cake probed by those techniques. Since the drying of paracetamol in methyl tert-butyl ether could be monitored using both techniques, the combined probe was used for monitoring this system, and multi-block PLSR analysis was conducted using both near-infrared and Raman spectra of combinations of the configurations. The multi-block PLSR model performance was similar to that of the individual SORS spectra, which was attributed to the stronger signals and spectral features of the Raman signal compared to the near-infrared measurements. Since the application of SORS for the monitoring of pharmaceutical drying was demonstrated and showed improvement in PLSR model performance and solvent content estimation, SORS was further used for the monitoring of the washing with methyl tert-butyl ether a paracetamol filter cake wet with anisole. The results similarly showed improved estimations of the content of both solvents in the filter cake from spectra from larger offset distances. The outcomes of the studies in this thesis demonstrate the advantage of the application of spatially resolved spectroscopy for monitoring the solvent content in pharmaceutical drying. The use of such novel process analytical technology offers potential for improved process monitoring and accurate prediction of the process end point.
Advisor / supervisor
  • Chen, Yi-chieh
  • Price, Chris
Resource Type
DOI

Relations

Items

Thumbnail Title Date Uploaded Visibility Actions
file details PDF of thesis T17081 2024-11-19 Public Download