Effect of salivary fluid characteristics on the physical features of in vitro bread bolus: From the absence of saliva to artificially simulated hypersalivation.

Saliva facilitates food oral processing, bolus formation, swallowing, and sensory perception, in addition to contributing to oral health and phonation. Ageing, health affections, and polymedication are among many causes altering salivary production, modifying the mastication process, the food impregnation ratio, and in turn altering the characteristics of the bolus, swallowing, and digestion. In this in vitro work, using the AM2 masticator apparatus, which replicates the mechanical actions taking place while chewing solid foods and produces realistic food bolus in various oral conditions, we investigated the effect of salivary fluid characteristics, i.e., composition, quantity (from absence to hypersalivation), temperature, and enzymatic action, on the physical characteristics (i.e., particle size distribution (PSD), bolus mass, salivary fluid content) of in vitro boluses of Traditional French baguette. A ready-to-swallow bolus of baguette displayed on average a d50 value (median particle size by mass) of 4.1 ± 0.4 mm, with saliva fluid constituting âˆ¼ 35 % of the final bolus mass. The absence of saliva in mouth led to a deficient oral processing, forming bread boluses constituted by extremely big particles (ca. 80 % of particles had a size > 7.1 mm) that likely cannot be swallowed safely. On the contrary, an excess of saliva favoured an excessive breaking down of bread, leading to bread boluses constituted by smaller particles than those formed under healthy salivary conditions (d50 decreased from 4.1 mm to 3.1 mm), having a higher salivary fluid content (+10 %). On the other hand, the salivary fluid temperature did not affect PSD, d50, bolus mass, or salivary fluid content of in vitro bread boluses, however, the addition of human salivary α-amylase did, favouring particle size reduction (d50 decreased to 2.6 mm). Therefore, beyond the correlation between bolus hydration by saliva and food properties such as hardness and moisture content, our findings indicate that the quantity of salivary fluid present in the oral cavity and the enzymatic activity of salivary α-amylase during bread mastication significantly influence both the particle size distribution and the fluid content of bread boluses, ultimately determining the physical properties of the bolus and, therefore, potentially impacting the subsequent swallowing process.

Benchmarking of a microgel-reinforced hydrogel-based aqueous lubricant against commercial saliva substitutes.

Xerostomia, the subjective sensation of 'dry mouth' affecting at least 1 in 10 adults, predominantly elders, increases life-threatening infections, adversely impacting nutritional status and quality of life. A patented, microgel-reinforced hydrogel-based aqueous lubricant, prepared using either dairy or plant-based proteins, has been demonstrated to offer substantially enhanced lubricity comparable to real human saliva in in vitro experiments. Herein, we present the benchmarking of in vitro lubrication performance of this aqueous lubricant, both in its dairy and vegan formulation against a range of widely available and employed commercial saliva substitutes, latter classified based on their shear rheology into "liquids", "viscous liquids" and "gels", and also had varying extensional properties. Strikingly, the fabricated dairy-based aqueous lubricant offers up to 41-99% more effective boundary lubrication against liquids and viscous liquids, irrespective of topography of the tested dry mouth-mimicking tribological surfaces. Such high lubricity of the fabricated lubricants might be attributed to their limited real-time desorption (7%) from a dry-mouth mimicking hydrophobic surface unlike the tested commercial products including gels (23-58% desorption). This comprehensive benchmarking study therefore paves the way for employing these microgel-based aqueous lubricant formulations as a novel topical platform for dry mouth therapy.

Paediatric solid oral dosage forms for combination products: Improving in vitro swallowability of minitablets using binary mixtures with pellets.

There is a growing interest in enhancing the acceptability of paediatric pharmaceutical formulations. Solid oral dosage forms (SODF), especially multiparticulates, are being considered as an alternative to liquid formulations, but they may compromise palatability when large volumes are required for dosing. We hypothesised that a binary mixture of multiparticulates for paediatric use, designed to increase the formulation maximum packing fraction, could reduce the viscosity of the mixture in soft food and facilitate swallowing. Using the Paediatric Soft Robotic Tongue (PSRT) - an in vitro device inspired by the anatomy and physiology of 2-year-old children - we investigated the oral phase of swallowing for multi-particulate formulations, i.e., pellets (350 and 700 µm particles), minitablets (MTs, 1.8 mm), and their binary mixtures (BM), by evaluating oral swallowing time, the percentage of particles swallowed, and post-swallow residues. We also conducted a systematic analysis of the effect of the administration method, bolus volume, carrier type, particle size, and particle volume fraction on pellets swallowability. The results demonstrated that the introduction of pellets affected the flowing ability of the carriers, increasing shear viscosity. The size of the pellets did not appear to influence particle swallowability but raising the particle volume fraction (v.f.) above 10% resulted in a decrease in the percentage of particles swallowed. At v.f. 0.4, pellets were easier to swallow (+ 13.1%) than MTs, being the administration method used highly dependent on the characteristics of the multi-particulate formulation under consideration. Finally, mixing MTs with only 24% of pellets improved particle swallowability, achieving swallowing levels similar to those of pellets alone. Thus, combining SODF, i.e., MTs and pellets, improves MT swallowability, and offers new possibilities for adjusting product palatability, being particularly attractive for combination products.

A novel soft robotic pediatric in vitro swallowing device to gain insights into the swallowability of mini-tablets.

Soft robotics could help providing a better understanding of the mechanisms underpinning the swallowability of solid oral dosage forms (SODF), especially by vulnerable populations such as the elderly or children. In this study a novel soft robotic in vitro device is presented, the Pediatric Soft Robotic Tongue (PSRT), inspired by the literature data on the anatomy and physiology of a 2-year-old child. Multi-particulate oral formulations (i.e., mini-tablets (MT)) were considered, including different scenarios such as SODF carrier (i.e., soft-food, liquid), administration methods, SODF size and volume fraction. In vitro results showed that semi-solid foods like yoghurt and apple puree (shear viscosity above âˆ¼ 150 mPa.s at γ̇ = 50 s-1, and its yield stress up to âˆ¼ 5 Pa) may be considered more suitable than thin liquids (i.e., xanthan gum 0.25 %) for swallowing MT. However, the reduction of MT size did not bring any benefit in terms of swallowability in the range studied. Regarding the administration method, spreading MT on top of a teaspoon full of carrier should be preferred over mixing MT with the carrier or placing MT on the tongue first to favour their swallowability. Finally, and under the in vitro conditions studied using yoghurt as carrier, it would be possible to increase the volume fraction of SODF up to 0.20 without influencing swallowability according to the three parameters evaluated (% of MT swallowed, bolus velocity, and post-swallow residues). These results should help to design more focused sensory and/or clinical tests to improve product formulation and patient acceptability.

Effect of Macroscopic Surface Heterogeneities on an Advancing Contact Line.

The shape of a liquid-air interface advancing on a heterogeneous surface was studied experimentally, together with the force induced by the pinning of the contact line to surface defects. Different surfaces were considered with circular defects introduced as arrays of cocoa butter patches or small circular holes. These heterogeneous surfaces were submerged in aqueous ethanol solutions while measuring the additional force arising from the deformation of the advancing contact line and characterizing the interface shape and its pinning on the defects. Initially, the submersion force is linear with submerged depth, suggesting a constant defect-induced stiffness. This regime ends when the contact line depins from the defects. A simple scaling is proposed to describe the depinning force and the depinning energy. As the defect separation increases, the interface stiffness is found to increase too, with a weak dependency on the defect radius. This interaction between defects cannot be captured by simple scaling but can be well predicted by a theory considering the interface deformation in the presence of a periodic arrays of holes. Creating a four-phase contact line by including solid defects (cocoa butter) reduced pinning forces. The radius of the defect had a nonlinear effect on the depinning depth. The four-phase contact line resulted in depinning before the defects were fully submerged. These experimental results and the associated theory help to understand quantitatively the extent to which surface heterogeneities can slow down wetting. This in turn paves the way to tailoring the design of heterogeneous surfaces toward desired wetting performances.

Effect of α-amylase and pH on the rheological properties of thickened liquids containing starch in in vitro conditions relevant to oral processing and swallowing.

The objective of this study was to investigate quantitatively the impact of saliva on the rheological properties of thickened drinks (IDDSI level 3) with different pH. Oral digestion was simulated and followed using a rheometer. An insalivation ratio measured from spitted boli, was used in the in vitro oral digestion experiments, comparing unstimulated human saliva to artificial saliva. The initial viscosity of thickened water samples (pH 5.3 and 7.4) was reduced by 80% after only 5 s of in vitro oral digestion. A similar viscosity decay was observed with the artificial saliva. This decrease in viscosity was attributed to the breakdown of the starch granule structure by α-amylase and in a lesser extent to a dilution effect. In contrast, the rheological properties of thickened lemon drink (pH = 2.7) and thickened orange juice (pH = 4.0) were not influenced significantly by human salivary amylase. These results suggest that at these pHs, starch-based thickened drinks can maintain their initial IDDSI level, despite a strong dilution with saliva, which could help in the management of dysphagia. Clinical trials should be performed to confirm this hypothesis. Only human salivary α-amylase should be used to study products between pH 3 and 5 to imitate the structural and rheological breakdown happening before swallowing, while α-amylase from Bacillus sp. could also be used outside this range. The method developed in this study can be used to quantify the impact of food oral processing and evaluate rheological properties relevant for swallowing in the presence of saliva.

Effect of the rheological properties of the liquid carrier on the in vitro swallowing of solid oral dosage forms.

Solid oral dosage forms (SODF) are the most popular oral drug delivery forms, but they can be difficult to swallow, especially for patients suffering from swallowing disorders. This study investigated the dynamics of different combinations of liquid carriers and SODF during the oral phase of swallowing using an in vitro model. The rheological properties of the carriers were characterized using shear and extensional rheometry, and their effect on bolus velocity, bolus shape, post-swallow residues, and SODF position within the bolus was evaluated. The latter has been identified as a novel and promising variable to discriminate between alternative formulations. When swallowed with water, capsules and tablets did not impact significantly the velocity of the bolus, but they lagged behind the liquid bolus, suggesting that low viscosity Newtonian fluids are not efficient carriers for SODF. Increasing the viscosity of the carrier at high shear rates improved the ability of the liquid to transport the SODF but also increased the amount of post-swallow residues. At equivalent shear viscosity, elastic and extensional properties of carriers influenced positively the position of the SODF in the bolus. Capsules and tablets were transported toward the front of these boluses, during the oral phase of swallowing, which is considered beneficial to avoid SODF sticking to the mucosa in the following stages of swallowing. Thin elastic liquids appear as an interesting option to promote safe swallowing of capsules and tablets. Clinical studies are, however, necessary to confirm this positive effect in healthy and dysphagic patients.

The role of extensional rheology in the oral phase of swallowing: an in vitro study.

Swallowing disorders deteriorate significantly the quality of life and can be life-threatening. Texture modification using shear thinning food thickeners has been proven to be effective in the management of dysphagia. Some studies have recently considered the positive role of cohesiveness, but there is still an insufficient understanding of the effect of the rheological properties of the liquid bolus on the dynamics of bolus transport, particularly when elasticity and extensional properties are combined with a shear thinning behaviour. This study combines steady shear, SAOS and capillary breakage extensional rheometry with an in vitro method to characterize the oral transport of viscoelastic liquids. Bolus velocity and bolus length were measured from exit in vitro experiments using image analysis and related to shear and extensional properties. A theory describing the bolus dynamics shows that the elastic and extensional properties do not influence significantly the oral transit dynamics. Conversely, in vitro results suggest that the extensional properties can affect the transition from the oral to the pharyngeal phase of swallowing, where thin, viscoelastic liquids lead to a fast transit, lower oral post-swallow residues and more compact bolus with a smoother surface, which may suggest a lower risk of fragmentation. This mechanistic explanation suggests that the benefit of the extensional properties of thin viscoelastic liquids in the management of dysphagia should be further evaluated in clinical trials.

Pouring of Grains onto Liquid Surfaces: Dispersion or Lump Formation?

This study considers the consequences of adding grains to an air-liquid interface from a funnel. Depending on the grain contact angle and liquid surface tension, the interface is found to support a single or multiple layers of grains, forming a granular stack. By continuing to add grains, the stacks grow until either the lower grains disperse in the liquid, or the complete stack breaks free from the surface and sinks as a dry powder lump. Herein, the effects of grain contact angle, density, and size on these processes are studied experimentally, and a theoretical analysis is given. The maximum number of grains contained in a floating stack and its critical depth are observed to increase as the grain size decreases. The maximum number of grains scales with the bond number (Bo) as Bo-1.82 when stack detachment is observed and with an exponent  -2.0 when grains disperse into the liquid. As a result of these different scaling exponents, a critical bond number above which grains wet and disperse can be identified. Favorable conditions for dispersion are achieved with larger grains and, to a lesser extent, by lower surface tension and contact angle. The critical bond number separating grain dispersion from lump formation increases with an increasing grain contact angle, thus providing a physical justification for increasing grain size with common processes such as granulation or agglomeration. Conversely, a quantitative framework to interpret the limitations in dispersing small grains is proposed, justifying the need for low contact angle or liquids with low surface tensions, both favored by the use of surfactants. The present findings have identified conditions under which lump formation occurs, and hence how these undesired phenomena can be avoided in applications requiring the efficient dispersion of grains across a liquid interface.

In vitro and sensory tests to design easy-to-swallow multi-particulate formulations.

Flexible dosing and ease of swallowing are key factors when designing oral drug delivery systems for paediatric and geriatric populations. Multi-particulate oral dosage forms can offer significant benefits over conventional capsules and tablets. This study proposes the use of an in vitro model to quantitatively investigate the swallowing dynamics in presence of multi-particulates. In vitro results were compared against sensory tests that considered the attributes of ease of swallowing and post-swallow residues. Water and hydrocolloids were considered as suspending vehicles, while the suspended phase consisted of cellulose pellets of two different average sizes. Both in vivo and in vitro tests reported easier swallow for smaller multi-particulates. Besides, water thin liquids appeared not optimal for complete oral clearance of the solids. The sensory study did not highlight significant differences between the levels of thickness of the hydrocolloids. Conversely, more discriminant results were obtained from in vitro tests, suggesting that a minimum critical viscosity is necessary to enable a smooth swallow, but increasing too much the carrier concentration affects swallowing negatively. These results highlight the important interplay of particle size and suspending vehicle rheology and the meaningful contribution that in vitro methods can provide to pre-screening multi-particulate oral drug delivery systems before sensory evaluation.

Modelling the microbial dynamics and antimicrobial resistance development of Listeria in viscoelastic food model systems of various structural complexities.

Minimal processing for microbial decontamination, such as the use of natural antimicrobials, is gaining interest in the food industry as these methods are generally milder than conventional processing, therefore better maintaining the nutritional content and sensory characteristics of food products. The aim of this study was to quantify the impact of (i) structural composition and complexity, (ii) growth location and morphology, and (iii) the natural antimicrobial nisin, on the microbial dynamics of Listeria innocua. More specifically, viscoelastic food model systems of various compositions and internal structure were developed and characterised, i.e. monophasic Xanthan gum-based and biphasic Xanthan gum/Whey protein-based viscoelastic systems. The microbial dynamics of L. innocua at 10 °C, 30 °C and 37 °C were monitored and compared for planktonic growth in liquid, or in/on (immersed or surface colony growth) the developed viscoelastic systems, with or without a sublethal concentration of nisin. Microscopy imaging was used to determine the bacterial colony size and spatial organisation in/on the viscoelastic systems. Selective growth of L. innocua on the protein phase of the developed biphasic system was observed for the first time. Additionally, significant differences were observed in the colony size and distribution in the monophasic Xanthan gum-based systems depending on (i) the type of growth (surface/immersed) and (ii) the Xanthan gum concentration. Furthermore, the system viscosity in monophasic Xanthan gum-based systems had a protective role against the effects of nisin for immersed growth, and a further inhibitory effect for surface growth at a suboptimal temperature (10 °C). These findings give a systematic quantitative insight on the impact of nisin as an environmental challenge on the growth and spatial organisation of L. innocua, in viscoelastic food model systems of various structural compositions/complexities. This study highlights the importance of accounting for system structural composition/complexity when designing minimal food processing methods with natural antimicrobials.

Powder wettability at a static air-water interface.

The reconstitution of a beverage from a dehydrated powder involves several physical mechanisms that determine the practical difficulty to obtain a homogeneous drink in a convenient way and within an acceptable time for the preparation of a beverage. When pouring powder onto static water, the first hurdle to overcome is the air-water interface. We propose a model to predict the percentage of powder crossing the interface in 45 s, namely the duration relevant for this application. We highlight theoretically the determinant role of the contact angle and of the particle size distribution. We validate experimentally the model for single spheres and use it to predict the wettability performance of commercial food powders for different contact angles and particles sizes. A good agreement is obtained when comparing the predictions and the wettability of the tested powders.

Glass transition accelerates the spreading of polar solvents on a soluble polymer.

We study the wetting of polymer layers by polar solvents. As previously observed, when a droplet of solvent spreads, both its contact angle and velocity decrease with time as a result of solvent transfers from the droplet to the substrate. We show that, when the polymer is initially glassy, the angle decreases steeply for a given value of the velocity, Ug. We demonstrate that those variations result from a plasticization, i.e., a glass transition, undergone by the polymer layer during spreading, owing to the increase of its solvent content. By analyzing previous predictions on the wetting of rigid and soft viscoelastic substrates, we relate Ug to the viscosity of the polymer gel close to the glass transition. Finally, we derive an analytical prediction for Ug based on existing predictions for the water transfer from the droplet to the substrate. Using polar solvents of different natures, we show that the experimental data compare well to the predicted expression for Ug.

Dynamic wetting on a thin film of soluble polymer: effects of nonlinearities in the sorption isotherm.

The wetting dynamics of a solvent on a soluble substrate interestingly results from the rates of the solvent transfers into the substrate. When a supported film of a hydrosoluble polymer with thickness e is wet by a spreading droplet of water with instantaneous velocity U, the contact angle is measured to be inversely proportionate to the product of thickness and velocity, eU, over two decades. As for many hydrosoluble polymers, the polymer we used (a polysaccharide) has a strongly nonlinear sorption isotherm φ(a(w)), where φ is the volume fraction of water in the polymer and aw is the activity of water. For the first time, this nonlinearity is accounted for in the dynamics of water uptake by the substrate. Indeed, by measuring the water content in the polymer around the droplet φ at distances as small as 5 µm, we find that the hydration profile exhibits (i) a strongly distorted shape that results directly from the nonlinearities of the sorption isotherm and (ii) a cutoff length ξ below which the water content in the substrate varies very slowly. The nonlinearities in the sorption isotherm and the hydration at small distances from the line were not accounted for by Tay et al., Soft Matter 2011, 7, 6953. Here, we develop a comprehensive description of the hydration of the substrate ahead of the contact line that encompasses the two water transfers at stake: (i) the evaporation-condensation process by which water transfers into the substrate through the atmosphere by the condensation of the vapor phase, which is fed by the evaporation from the droplet itself, and (ii) the diffusion of liquid water along the polymer film. We find that the eU rescaling of the contact angle arises from the evaporation-condensation process at small distances. We demonstrate why it is not modified by the second process.