An in vitro experiment to simulate how easy tablets are to swallow.

The compliance of patients to solid oral dosage forms is strongly conditioned by the perceived ease of swallowing, especially in geriatric and pediatric populations. This study proposes a method, based on an in vitro model of the human oropharyngeal cavity, to study quantitatively the oral phase of human swallowing in presence of single or multiple tablets. The dynamics of swallowing was investigated varying the size and shape of model tablets and adjusting the force applied to the mechanical setup to simulate tongue pressure variations among individuals. The evolution of the velocity of the bolus, the oral transit time, and the relative position of the solid oral dosage form within the liquid bolus were measured quantitatively from high speed camera recordings. Whenever the solid dosage forms were big enough to interact with the walls of the in vitro oral cavity, a strong effect of the volume of the medication in respect of its swallowing velocity was observed, with elongated tablets flowing faster than spherical tablets. Conversely, the geometrical properties of the solid oral dosage forms did not significantly affect the bolus dynamics when the cross section of the tablet was lower than 40% of that of the bolus. The oral phase of swallowing multiple tablets was also considered in the study by comparing different sizes while maintaining a constant total mass. The predictive power of different theories was also evaluated against the experimental results, providing a mechanistic interpretation of the dynamics of the in vitro oral phase of swallowing. These findings and this approach could pave the way for a better design of solid oral medications to address the special needs of children or patients with swallowing disorders and could help designing more successful sensory evaluations and clinical studies.

In vivo observations and in vitro experiments on the oral phase of swallowing of Newtonian and shear-thinning liquids.

In this study, an in vitro device that mimics the oral phase of swallowing is calibrated using in vivo measurements. The oral flow behavior of different Newtonian and non-Newtonian solutions is then investigated in vitro, revealing that shear-thinning thickeners used in the treatment of dysphagia behave very similar to low-viscosity Newtonian liquids during active swallowing, but provide better control of the bolus before the swallow is initiated. A theoretical model is used to interpret the experimental results and enables the identification of two dynamical regimes for the flow of the bolus: first, an inertial regime of constant acceleration dependent on the applied force and system inertia, possibly followed by a viscous regime in which the viscosity governs the constant velocity of the bolus. This mechanistic understanding provides a plausible explanation for similarities and differences in swallowing performance of shear-thinning and Newtonian liquids. Finally, the physiological implications of the model and experimental results are discussed. In vitro and theoretical results suggest that individuals with poor tongue strength are more sensitive to overly thickened boluses. The model also suggests that while the effects of system inertia are significant, the density of the bolus itself plays a negligible role in its dynamics. This is confirmed by experiments on a high density contrast agent used for videofluoroscopy, revealing that rheologically matched contrast agents and thickener solutions flow very similarly. In vitro experiments and theoretical insights can help designing novel thickener formulations before clinical evaluations.

Impact of gastric pH profiles on the proteolytic digestion of mixed ßlg-Xanthan biopolymer gels.

The understanding of how foods are digested and metabolised is essential to enable the design/selection of foods as part of a balanced diet. Essential to this endeavour is the development of appropriate biorelevant in vitro digestion tools. In this work, the influence of gastric pH profile on the in vitro digestion of mixtures of ß-lactoglobulin (ßlg) and xanthan gum prior to and after heat induced gelation was investigated. A conventional highly acidic (pH 1.9) gastric pH profile was compared to two dynamic gastric pH profiles (initial pH of 6.0 vs. 5.2 and H(+) secretion rates of 60 vs. 36 mmol h(-1)) designed to mimic the changes in gastric pH observed during clinical trials with high protein meals. In moving away from the pH 1.9 model, to a pH profile reflecting in vivo conditions, the initial rate and degree of protein digestion halved during the first 45 minutes. After 90 minutes of gastric digestion, all three pH profiles caused similar extents of protein digestion. Given that 50% gastric emptying times of (test) meals are in range of 30-90 min, it would seem highly relevant to use a dynamic pH gastric model rather than a pH 1.9 (USP) or pH 3 model (INFOGEST) in assessing the impact of food structuring approaches on protein digestion. The impact that heat induced gelation had on the degree of gel digestion by pepsin was also investigated. Surprisingly, it was found that heat induced gelation of ßlg-xanthan mixtures at 70-90 °C for 20 minutes lead to a considerable decrease in the rate of proteolysis, which contrasts many studies of dispersed aggregates and gels of ßlg alone whose heating accelerates pepsin activity due to unfolding. In the present case, the formation of a dense protein network created a fine pore structure which restricted pepsin access into the gel thereby slowing proteolysis. This work not only has implications for the in vitro assessment of protein digestion, but also highlights how protein digestion might be slowed, learnings that might have an influence on the design of foods as part of a satisfying balanced diet.

A model experiment to understand the oral phase of swallowing of Newtonian liquids.

A model experiment to understand the oral phase of swallowing is presented and used to explain some of the mechanisms controlling the swallowing of Newtonian liquids. The extent to which the flow is slowed down by increasing the viscosity of the liquid or the volume is quantitatively studied. The effect of the force used to swallow and of the gap between the palate and the roller used to represent the contracted tongue are also quantified. The residual mass of liquid left after the model swallow rises strongly when increasing the gap and is independent of bolus volume and applied force. An excessively high viscosity results in higher residues, besides succeeding in slowing down the bolus flow. A realistic theory is developed and used to interpret the experimental observations, highlighting the existence of an initial transient regime, at constant acceleration, that can be followed by a steady viscous regime, at constant velocity. The effect of the liquid viscosity on the total oral transit time is lower when the constant acceleration regime dominates bolus flow. Our theory suggests also that tongue inertia is the cause of the higher pressure observed at the back of the tongue in previous studies. The approach presented in this study paves the way toward a mechanical model of human swallowing that would facilitate the design of novel, physically sound, dysphagia treatments and their preliminary screening before in vivo evaluations and clinical trials.

Matching the rheological properties of videofluoroscopic contrast agents and thickened liquid prescriptions.

In the treatment of oropharyngeal dysphagia, the link between diagnosis and prescription of thickened liquids that are safe to swallow is not always straightforward. Frequently, the capacity to objectively assess and quantify the rheological properties of diagnostic test fluids and to select "rheologically equivalent" dietary products is missing. Perhaps sometimes the importance of an objective comparison is not fully appreciated because two liquids seem reasonably similar in a subjective comparison (e.g., flow from a spoon). The present study deals with some of these issues. Shear viscosity measurements were used to characterize the flow behavior of videofluoroscopic contrast agents and of thickened fluids prepared with commercial thickening agents. Effects of time and composition of the different fluids were analyzed regarding shear-rate-dependent viscosity. Nearly all materials tested showed a pronounced dependence of viscosity with shear rate ("shear thinning"). Results confirm that it is feasible (but not always straightforward) to "match" the viscosities of diagnostic fluids and thickened beverages if certain precautions are taken. For example, the time required to reach final viscosity levels can be significant for some thickeners, particularly when used with liquids containing contrast agents. It is recommend to use only diagnostic materials and thickening agents for which reliable viscosity data are available.