University of Cambridge
Investigating the Hydration and Disintegration Mechanisms of Film-Coated Pharmaceutical Tablets
Abstract
dc:description.abstractThe pharmaceutical tablet is the most common solid oral dosage form to administer drug or active pharmaceutical ingredient (API) to patients. Tablets are often film-coated with a layer of polymeric material to protect the drug from environmental degradation, facilitate the packaging process, and enhance patient compliance. However, the mechanisms of hydration, disintegration and subsequent drug release and dissolution of a film-coated tablet are not fundamentally understood. To investigate the mechanisms, flat-faced tablets with a diameter of 13 mm and a thickness between 1.5 mm and 1.6 mm were directly compressed, and an immediate release film coating layer with a thickness between 80 μm and 160 μm was applied to one face of these tablets. This tablet geometry and film coating were chosen as a model system to understand how water interacts with the film coating and the tablet core. Microcrystalline cellulose, anhydrous lactose, monohydrate lactose, mannitol, and/or magnesium stearate at specified mass fractions were used as the components of the tablet core. The film coating system was either a ready-to-use polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC) based immediate release formulation or a sustained release formulation based on ethylcellulose. Each of these film coating systems contains various polymers. The film-coated tablet hydration and disintegration processes were studied using terahertz pulsed imaging (TPI), while optical coherence tomography (OCT) was used to capture further details on the swelling process of the polymer and the interfacial changes during the hydration of film-coated tablet. To generalise the methodology, tablets with a different geometry (e.g., 10 mm diameter, convex shape, surface with debossing) were also studied via TPI, while the TPI-OCT methodology using the flat-faced model system was briefly generalised to investigate the hydration of sustained release film-coated tablets. The TPI and OCT techniques principally investigated two aspects: the film coating polymer dissolution process and the subsequent water transport process in the tablet core following coating dissolution. The film coating was found to act as a temporary mass transport barrier that prevented capillary water transport before the barrier becomes more water-permeable due to coating polymer solubilisation. A three-parameter correlation between the film coating dissolution time, coating thickness and coating density was established to quantify this barrier effect. During the coating dissolution process, the anhydrous-to-hydrate transformation was discovered in the tablet core for the first time, which can potentially alter the crystalline structure in the tablet core and directly affect the subsequent tablet disintegration. Moreover, the role of film coating formulation, tablet core formulation, tablet shape/diameter, and dissolution medium temperature were assessed to develop the film-coated tablet hydration and disintegration mechanisms. These findings demonstrate that the TPI and OCT are robust process analytical technologies to examine the film-coated tablet disintegration process. Results can not only help predict the dissolution of film coating within the typical range of thickness (30 μm and 40 μm) and potentially be extended to understand modified release formulations, but also enhance fundamental understanding between water and the film-coated tablet matrix in order to assist the predictive modelling and digital manufacturing of pharmaceutical tablets.
Degree
thesis:*- Name dc:type.qualificationname
- Doctor of Philosophy (PhD)
- Level dc:type.qualificationlevel
- Doctoral
- Grantor dc:publisher.institution
- University of Cambridge
- Year dc:date.issued
- 2025
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Ma, Mingrui
- Advisor dc:contributor.advisor
-
- Zeitler, J Axel
Subjects
dc:subject × 9Rights
dc:rightsIdentifiers
dc:identifier.*- Author Identifier
- 0000-0003-4373-9596
- OAI identifier oai:identifier
- oai:www.repository.cam.ac.uk:1810/391732