Thesis
Understanding and mitigating agglomeration and attrition during the drying of Paracetamol
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2023
- Thesis identifier
- T16738
- Person Identifier (Local)
- 201876271
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Oral dose formulation is quite common for most commercial pharmaceutical products. The performance of a drug product is mainly dependent on the physical properties of the active pharmaceutical ingredient (API). As such, great care is taken during the production of the API to achieve a target particle size distribution. Control of the API particle‐size distribution is traditionally achieved via the crystallization process. A significant amount of effort goes into designing crystallization processes that consistently produce the desired API properties on scale‐up. The isolation (filtration, washing, and drying) process is needed to separate the pure product crystals from the impure mother liquor to produce dry, free-flowing particles while preserving the particle size distribution achieved by crystallization. Drying is the last and critical processing step in the isolation and purification of API crystals which is performed to remove the residual solvent remaining after filtration and washing. The effectiveness of the drying process affects the quality attributes of the final drug product. Traces of residual solvent may also affect the stability of the formulated product. Any API dissolved in the residual solvent left during drying tends to create "sticky" points at the contacts between particles, promoting solid bridges and being responsible for particle agglomeration. The residual moisture content and composition, solvent polarity, surface tension, and viscosity significantly impact agglomeration. The drying process can also impact the particle‐size distribution of the API, which affects the stability, bioavailability, dissolution rate and content uniformity of the drug product and the reproducibility of the manufacturing process. The main aim of this work was to explore the role of residual solvent during drying by quantifying the threshold limit of the residual moisture content and the dissolved material to form a robust agglomerate. Based on using a model API, paracetamol, the results indicating the minimum API mass that can cause agglomeration is helpful information to support the design of filter cake-washing processes to avoid agglomeration. This research also addresses the work done for developing a convenient method for quantifying agglomerate brittleness based on experimental validation. Further objectives include the work done to analyze the interaction and transport of residual solvent with API during drying by evaluating the role of contact angles and capillary forces to understand the transport of residual moisture and the dissolved material during drying. The final component was the development of a semi-empirical approach based on the correlation of material properties and breakage assessment tests to provide a corresponding scale-down concept/apparatus for mimicking particle breakage in agitated dryers at various scales.
- Advisor / supervisor
- Price, C. J. (Christopher John)
- Mulheran, Paul
- Resource Type
- DOI
- Date Created
- 2022
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