Thesis
From particle to tablet : understanding long-term physical stability of immediate-release tablets
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2026
- Thesis identifier
- T17569
- Person Identifier (Local)
- 202283051
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Understanding how excipient properties evolve under storage conditions and how these changes impact tablet performance is crucial for designing physically stable oral solid dosage forms (OSDFs). However, the relationship between stability rate processes at the particle and tablet scales remains insufficiently understood, limiting predictive capabilities of how early particle-level changes translate to long-term tablet properties such as mechanical integrity, moisture uptake, and disintegration performance. This thesis presents a multi-scale investigation into how excipient-level changes, particularly moisture sorption and swelling, determine the stability of directly compressed immediate-release (IR) tablets over time. At the particle level, dynamic vapour sorption (DVS) was used to characterise excipient responses to controlled humidity exposure across eight materials. Sorption kinetics and equilibrium moisture contents were quantified under varying temperature and humidity conditions. Particle imaging revealed irreversible swelling for disintegrants such as croscarmellose sodium (CCS) and sodium starch glycolate (SSG), and partial reversibility for microcrystalline cellulose (MCC), establishing the mechanistic basis for particle-level storage responses. The study then scaled these insights to the tablet level using MCC and MCC-CCS binary formulations prepared at different porosities by direct compression. By combining DVS data with real-time storage, scaling factors were established that link early DVS data to long-term uptake behaviour, allowing prediction of both equilibrium and kinetic parameters at the tablet level. Structural consequences, including rapid losses in tensile strength and porosity, most pronounced on the first day of storage, were captured within this framework, demonstrating its ability to connect accelerated particle-level data with tablet-scale stability. Finally, formulation complexity was introduced through the addition of magnesium stearate and lactose. These excipients generated new interactions that markedly altered disintegration behaviour, extending beyond the influence of porosity and mechanical strength. The results demonstrated that liquid absorption and wetting kinetics are more reliable predictors of post-storage disintegration than tensile strength. In parallel, applying the predictive framework for time-scale translation of moisture uptake to these multi-component systems provided a robustness test, confirming its applicability beyond simple binary formulations. These investigations enabled the tracking of the timeline upon which storage-driven physical changes occurred, distinguishing between effects triggered by early moisture exposure and those emerging during prolonged storage. The rate of tensile strength loss was also estimated and shown to correlate with the kinetics of moisture uptake, further reinforcing the predictive basis of the framework. Together, this work establishes a particle-to-tablet approach for understanding the physical stability of IR tablets. By bridging DVS-derived sorption dynamics with real storage ones, validating this time-scale translation across both simple and complex formulations, and identifying early versus prolonged moisture exposure-driven changes, the thesis provides a practical foundation for rational excipient selection, predictive modelling and accelerated formulation development.
- Advisor / supervisor
- Markl, Daniel
- Resource Type
- DOI
- Date Created
- 2025
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