Toward the Optimal Choice of Gelled Vehicles for Oral Drug Administration in Dysphagic Patients

Abstract

Background/Objectives: Thickened waters are commonly used for dysphagic patients to ensure hydration, facilitate safer swallowing, and administer oral therapies, yet their impact on drug dissolution remains unclear. This study aims to investigate how thickening agents, viscosity, and solid oral dosage form (SODF) formulations influence drug release in gelled vehicles.

Methods: Twelve commercially available thickened waters, including both ready-to-use products and powders for extemporaneous preparation, were used to disperse crushed sodium pravastatin tablets. The resulting preparations were evaluated for their rheological properties and dissolution performance.

Results: Thickened water products vary in consistency, with starch-based thickeners providing more consistent results than gum-based ones. Pravastatin release profiles closely matched the original tablets with starch thickeners, while gum-based thickeners showed greater variability, primarily influenced by viscosity.

Conclusions: These findings emphasize the importance of selecting the appropriate thickening agent for controlling drug release in thickened water products, highlighting the need to balance patient compliance with the potential impact on drug release during product development.

Introduction

Thickened waters (also referred to as gelled waters or, more generally, thickened beverages) are water or other liquids (sometimes juices) that were modified by the addition of thickening agents to achieve a specific viscosity. From a regulatory perspective, thickened waters may be classified as food for special medical purposes (FSMPs) under EU Regulation No. 609/2013 [1], provided they are intended to meet the specific nutritional requirements of patients with impaired capacity to consume ordinary foodstuffs.

The modification of beverage consistency makes liquids easier and safer to swallow for individuals with swallowing difficulties, such as those suffering from dysphagia, who often struggle with certain consistencies, particularly solid foods and thin liquids [2,3]. For these individuals, thickened waters help ensure proper hydration while reducing the risk of aspiration and choking by providing a controlled consistency [4,5]. Several associations involved in the management, therapy, and support of dysphagic patients provided recommendations on using liquids with appropriate viscosity or consistency to reduce the risk of aspiration pneumonia [6].

Currently, the proper consistency of thickened waters is ensured by adherence to the NDD (National Dysphagia Diet) guidelines established by the American Dietetic Association and the National Dysphagia Diet Task Force [7], or to the IDDSI (International Dysphagia Diet Standardisation Initiative) recommendations, developed by an international multidisciplinary group (IDDSI Committee) supported by numerous International Reference Groups [8]. The market currently offers various thickened waters available in two forms: ready-to-use thickened liquids (RU_TL) and formulated powders designed for the extemporaneous preparation of thickened liquids (EP_TL).

In both cases, the desired consistency is achieved through the use of thickening agents, which are polysaccharides belonging to the group of modified starches or gums. Among the starches, pregelatinized starches are commonly used for preparing thickened beverages, typically derived from corn starch, although alternatives, such as those sourced from potatoes, are also commercially available. On the other hand, the most commonly used gums include xanthan gum, guar gum, and other gum-like polysaccharides, such as carrageenan and pectin. In gum-based products, these agents are typically used in combination to achieve optimal consistency and functionality [9,10]. The use of liquids with appropriate consistency is the most suitable approach for dysphagic patients, except for those unable to swallow or in cases where oral nutrition does not ensure proper hydration. In such situations, an enteral nutrition strategy, such as administration via a nasogastric tube or percutaneous endoscopic gastrostomy, is required [11].

Thickened waters are used not only for hydration but also for administering the oral therapies when alternative dosage forms suitable for dysphagic, such as suppositories or transdermal patches, are not commercially available. A common practice in dysphagic patients is to crush tablets or open capsules, then disperse or dissolve their contents in modified-consistency beverages [10,12]. This practice can modify drug bioavailability by influencing the drug release process, due both to the manipulation of the solid oral dosage form (SODF) and the interaction of the dispersed powder with the thickened vehicle. While the effects of manipulating the SODF were extensively studied in the literature [12,13,14,15], the latter aspect requires further investigation and clarification.

Currently, there are few studies focusing on this aspect. Manrique et al. reported a reduction in the release rate of several drugs when crushed tablets were dispersed in gum-based and starch-gum-based vehicles, hypothesizing that the effect was due to the consistency and/or structure of the carrier vehicles [16,17]. Similar findings was reported by Ilgaz et al., which demonstrated that the gelling vehicles significantly influences the drug’s dissolution rate, especially in thickened samples prepared with xanthan gum [18]. These studies highlight that the gelled vehicles affect the dissolution rate of the drugs. However, several aspects remain to be clarified. First, although all the studies suggest a relationship between the reduction in dissolution rate and viscosity, this correlation has never been conclusively proven.

Additionally, the number of commercial thickened waters analyzed was limited, despite the wide variety of products available on the market. These include both ready-to-use thickened liquids (RU_TL), which may come in a single consistency or in multiple consistency grades, and formulated powders designed for the extemporaneous preparation of thickened liquids (EP_TL). Moreover, most commercial products are gum-based, containing thickening agents such as guar gum, xanthan gum, carrageenan, and pectin, typically used in blends. However, starch-based products are also available. The effect of the type of thickening agent (gum-based or starch-based) remains unclear, although some authors suggest that starch-based products have a lesser impact on the drug release rate. Finally, it remains to be clarified whether the reduction in the drug release rate is exclusively due to the gelled vehicles or if it can also be partially attributed to the amount of SODF added or their formulation (the presence of specific excipients).

This study aims to address existing knowledge gaps by clarifying how thickening agents (gum-based vs. starch-based), viscosity, and SODF formulation (including excipients) influence drug dissolution in gelled vehicles. To achieve this aim, four ready-to-use thickened liquids (one available in three different consistencies) and two formulated powders for extemporaneous preparation of thickened liquids (gum- and starch-based) were selected, for a total of twelve different gelled vehicles. Tablets of sodium pravastatin (PraNa) were chosen as the model drug, given their frequent use among the elderly population, who are most likely to experience swallowing difficulties or disorders. The selection was also motivated by the drug’s high water solubility and its availability as immediate-release tablets. Additionally, the availability of several equivalent medicinal products allows testing across different formulations, including both coated and uncoated tablets.

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Table 1. General information and abbreviations of all thickened water products used in manuscript.

Logrippo, S.; Ganzetti, R.; Sestili, M.; Perinelli, D.R.; Cespi, M.; Bonacucina, G. Toward the Optimal Choice of Gelled Vehicles for Oral Drug Administration in Dysphagic Patients. Pharmaceutics 2025, 17, 251. https://doi.org/10.3390/pharmaceutics17020251

Read also our introduction article on Gellan Gum here: