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Title: In vitro models for the formulation of easy-to-swallow products
Author: Marconati, Marco
ISNI:       0000 0004 7967 3098
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2019
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Cerebrovascular and neurodegenerative diseases are clinical conditions increasingly observed in geriatric populations. A common symptom of these pathologies is represented by the increased difficulty with food manipulation and intake. Developing food products, dietary supplements and oral medications for this set of patients requires an improved understanding of the interplay between bolus rheology, tongue coordination and lubrication of the oral cavity and their effect on the resulting ease of swallowing. This study employs an in vitro model experiment to elucidate the role of bolus rheology and to describe the oral swallowing dynamics in presence of suspended particles, to mimic swallowing of solid oral dosage forms. The model was first used to test viscoelastic liquids to validate the hypothesis that elasticity can contribute to a smoother bolus flow in the transition between the oral and the pharyngeal phase of swallowing. In this respect, the experimental results confirmed the effectiveness of thin viscoelastic liquids. These consistently led to a measurable reduction in bolus fragmentation at the ejection from the in vitro oral cavity without however significantly delaying the overall oral transit time. Conversely, model thick elastic liquids noticeably increased the measured oral transit times and led to an increased quantity of post-swallow residues. These results suggests the existence of an optimum range of rheological properties in vitro to secure the best balance between bolus fragmentation and bolus velocity. This finding, if confirmed in vivo could help designing novel products with elastic properties for a better management of swallowing disorders. Attention was then dedicated to the study of the alterations to the in vitro swallowing dynamics resulting from the presence of suspended tablets and multiparticulates. This topic was developed in relation to the peculiar needs of paediatric and geriatric populations that require a high dose flexibility and often show a reduced acceptance towards large solid oral dosage forms. Based on the theoretical results reported for simpler peristaltic flow, the study aimed at quantifying the additional pumping effort required for swallowing single and multiple tablets as a function of their physical attributes. in vitro tests confirmed that model-tablets with a larger cross section in the direction of swallowing consistently delayed the bolus flow. The viscosity of the suspending vehicle was also an important factor: thicker liquid media were able to ensure a smoother flow in vitro, even for large solid oral dosage forms. This finding confirms the effectiveness of thickened liquids as suspending vehicles for the oral administration of tablets and capsules. The importance of the suspending vehicle rheology was further highlighted with a combined in vitro and sensory study that considered the swallow-ability of placebo multiparticulates. The in vitro model provided a higher discrimination ability among the different formulations. This helped to clarify the results obtained from the 30 untrained healthy volunteers recruited for the sensory tests. Whilst confirming its utility, the study also pointed out some of the limitations of the in vitro model that consistently over-predicted the viscosity for smooth swallowing, compared to the in vivo data. This led to the development of a novel experimental setup, inspired by the functionality of the tongue, and capable of tackling a significant number of the limitations observed for previous in vitro studies of swallowing. This three dimensional model, can handle liquid boli spanning a wide range of consistencies and the soft robotic actuation can also be tailored to provide insights on the role of poor tongue coordination. The availability of this model allows to greatly extend the kinematic and dynamic comparison with clinical data and can allow for a more in-depth investigation of the role of oral lubrication in the bolus transport.
Supervisor: Ramaioli, Marco Sponsor: Nestlé Health Science
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral