Thesis
An alternative way of drying : supercritical CO2 extraction/drying for fast and effective removal of organic solvents from an active pharmaceutical ingredient
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2024
- Thesis identifier
- T17041
- Person Identifier (Local)
- 201665812
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- This research investigates supercritical carbon dioxide (scCO2) technology as an alternative way of efficiently drying active pharmaceutical ingredients (APis). Potential benefits of this green process technology include the minimisation of the solvent residues in the drug substance to a degree not achievable by conventional methods, milder process conditions and shorter drying times, which might lead to more energy-effective process. Another benefit for pharmaceutical materials processed in organic solvents is that using supercritical CO2 offers a possible route to a sterile product. -- This study conducts a comparative experimental analysis between supercritical CO2 extraction/ drying and conventional drying using an agitated filter dryer (AFD). The focus of this research is the removal of a challenging organic solvent, named dodecane, from paracetamol cakes. Apart from the drying performance, the study also evaluates the final product properties and energy consumption associated with each method. To conduct this experimental analysis, a Design of Experiments (DOE) methodology is employed to optimise both the conventional drying and supercritical CO2 treatment. In conventional drying, critical parameters such as temperature (50-70 °C), N2 flow rate (0.2-0.8 L/min), solid loading (60-150 g), and drying mode (static or agitated) are systematically studied, while maintaining a fixed pressure of 500 mbar. In the case of supercritical CO2 treatment, the study focuses on optimising temperature (50-70 °C), pressure (80-200 bar), CO2 flow rate (10-30 g/min) and solid loading (60- 150 g). -- The findings revealed that, in the case of the AFD, the solid loading significantly influenced the drying performance. Dodecane residues were successfully reduced down to 8 · 10-:³ mg/ g within a drying period of 3 hours using a 60 g cake sample. In contrast, 150 g cakes failed to meet the defined criteria (> 12.5 mg/ g) even after an extended drying period of 5 hours. Supercritical CO2 treatment consistently minimised the solvent concentrations (2 · 10-:3 to 25 · 10-:3 mg/ g) across various cake sizes, demonstrating faster (2 to 4 hours) and more complete drying than the conventional method. Particle size changes in particular agglomeration were observed in both drying techniques, but scCO2 resulted in softer agglomerates with a higher brittleness index. The best combination of factors in the case of the AFD was 60 g cake, 70 °C, 0.8 L/min N2 flow rate and intermittent agitation. For the scCO2 extraction/ drying, the optimal conditions were 150 g cake, 200 bar, 60 °C, and 20 g/min CO2 flow rate. Finally, the energy analysis showed that scCO2 technology was substantially more energy-efficient than AFD. At the optimal conditions, the normalised energy consumption for scCO2 was around 21 kWh/kg solids/kg solvent, whereas AFD required a considerably higher energy input of 147 kWh/kg solids/kg solvent.
- Advisor / supervisor
- Robertson, John
- Price, Chris J.
- Resource Type
- DOI
关系
项目
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PDF of thesis T17041 | 2024-08-19 | 公开 | 下载 |