Modified Diets and Medication in Dysphagia – The effect of thickener on drug bioavailability: A systematic review

Modified Diets and Medication in Dysphagia – The effect of thickener on drug bioavailability: A systematic review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Modified Diets and Medication in Dysphagia – The effect of thickener on drug bioavailability: A systematic review Jayne Atkin, Christopher Devaney, Yuki Yoshimatsu, David Smithard This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3199117/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Introduction Dysphagia is associated with long-term conditions including strokes, dementia, Parkinson’s disease and frailty. Dysphagia affects 30-40% of the population aged over 65-years-old. Adults with dysphagia are likely to experience long-term conditions requiring multiple medications (often >5) to manage this. The thickening of liquids is a common compensatory strategy in dysphagia management. Studies suggest that immersion in thickened liquids affects medicines’ solubility in vitro. Clinicians and pharmacists are unaware of the pharmacokinetic/therapeutic effects of thickened liquids on oral medicines. We conducted a systematic review of existing literature on thickeners’ effects on drug bioavailability. Methodology We performed a literature search of MEDLINE and EMBASE. Search terms included: dysphagia/thickened diet (EMBASE only)/ bioavailability or absorption of medicines or pharmacokinetics; excluded: NG feeds/animal studies. Studies included: all genders, countries, >18 years, community and hospital settings. PRISMA guidance was followed. Results 526 results were found and 15 articles identified following reference list review. Following abstract review, 508 were rejected. 33 received a full text review, 18 were rejected, and the remaining 15 included. Most articles evaluated the effect of thickeners on dissolution profiles of medications in-vitro. Few studies assessed bioavailability or used clinical outcome measures. Often these were small studies on limited numbers of medications. Conclusion Despite dysphagia and polypharmacy being common in older adults, little is known about the effects of altering liquid viscosity on the pharmacokinetics and therapeutic effect of most medications. Small single-centre studies suggest that immersion in thickener may negatively affect drug pharmacokinetics and therapeutic outcomes. dysphagia swallowing thickener modified-diets thickened-liquids bioavailability Figures Figure 1 Key Summary Points Aim: to understand further the effect of thickener on medications and their pharmacokinetic and therapeutic profiles, using a literature search. Findings: Despite dysphagia and polypharmacy being common in older adults, little is known about the effects of altering liquid viscosity on the pharmacokinetics and therapeutic effect of most medications. Message: further work must be undertaken to support clinicians, pharmacists and patients in understanding the effects of thickener. Introduction In England more than 1 in 10 people over 65 years take at least eight different prescribed medications each week. This increases as people get older – to nearly 1 in 4 in the over 85’s [1]. Dysphagia is a geriatric syndrome associated with many common long-term clinical conditions including stroke, dementia, Parkinson’s disease and frailty. Clave et al report that oropharyngeal dysphagia may affect 30 to 40% of the population aged 65 years or more. They also report that dysphagia affects more than 50% of people living in nursing homes [2]. Castellanos et al found that 8.3% of residents in nursing home facilities received thickened fluids [3]. Thickening fluids is an increasingly used strategy to reduce the risk of aspiration. The increased viscosity of fluids compensates for a swallowing deficit by slowing down the flow of the fluid from the mouth to the oropharynx – allowing time for glottis closure [4]. Steele et al performed a systematic review on the effect of food texture and liquid consistency modification on swallowing physiology and function, they concluded that there is a clear reduction in the risk of aspiration as liquids progress from thin to very thick (studies involving barium swallow under video fluoroscopy in adults with dysphagia) [5]. Given the overlapping profiles of those patients prescribed multiple medications and those receiving thickened fluids, understanding the interactions between thickened fluids and medications and how this may affect medication bioavailability and therapeutic effect is essential. Thickening agents can be broadly classified into 3 groups: starch based, guar gum based and xanthan gum based, often chosen based on their cost, availability, consistency and flavour. There is variability in how thick fluids are that patients receive. In 2012 the international dysphagia diet standardisation initiative was founded and the characteristics of fluids, thickened fluids and foods were described. The level of viscosity of fluids ranges from 0 (thin) to 4 (extremely thick) [6]. There have been a few studies reporting the effect of thickeners on drugs, but no systematic review has been performed. We have conducted a systematic review to answer the question of whether thickened fluids affect the bioavailability of oral medications. Furthermore, whether the level of thickness of fluids, the type of thickener used and the duration of emersion in thickened fluid affects bioavailability of medications. Additionally, we have reviewed evidence as to whether the bioavailability and therapeutic effect of various medications are differentially affected by thickener. Methodology PRISMA methodology was followed to structure the review [7] (see Fig. 1). An experienced librarian performed a literature search of MEDLINE and EMBASE. Search terms included: dysphagia AND bioavailability OR absorption of medicines OR pharmacokinetics AND (with either) Parkinson’s / antibiotic / epilepsy / antiviral / thickened diet (EMBASE only). Two of the authors screened search results (titles and abstracts, duplicates were removed at this stage). No software was used in this process. The terms ‘Parkinson’s’, ‘antibiotic’ ‘epilepsy’ and ‘antiviral’ were included so that we could focus our search on time critical medications and medications that have a critical impact on clinical outcomes. However, when evaluating search results, we have included all medications due to the small number of studies in this field. We excluded unrelated articles, review articles and conference abstracts. We also excluded animal studies and articles relating to nasogastric / percutaneous endoscopic gastrostomy feeds. All articles included were peer reviewed published articles. All ages over 18 years were included in both community and hospital settings. No articles were excluded based on type of medication. Articles describing in vitro experiments were also included. Articles selected for a full review were selected independently and then agreed by both authors. Reference lists from these articles were reviewed and further relevant articles were identified. There was no discrepancy in selected articles. All relevant articles were then summarised according to study design, number of participants, method and main conclusions. Results 526 results were found on the initial search. A further 15 articles were identified by the authors following reviews of reference lists. Following review of the abstracts (performed independently by 2 of the authors) 508 publications were rejected. 33 received a full text review and a further 18 were rejected, with the remaining 15 articles included in the review. All studies reviewed were small single centre studies. The rationale for rejecting studies included study design (e.g., animal studies), study type (e.g., review articles and conference abstracts). Fifteen papers published between 1984 and 2021 were reviewed (outlined in table 1). Five studies were in vivo and the remaining 10 studies were in vitro. Table 1: Summary of articles included for review Author, Year Title Study Design Participants Method Main Conclusions Huupponen et al 1984 Effect of Guar Gum, a Fibre Preparation, on Digoxin and Penicillin Absorption in Man Double blind study N = 10 Volunteers received either digoxin or penicillin, medication was taken with either guar gum or a placebo preparation (wheat germ) mixed with 200mls of water. Serum and urine concentrations of digoxin were measured by radioimmunoassay. Serum penicillin concentrations were measured microbiologically according to Reeves et at (1978) Mean peak digoxin concentration was lower after guar gum than after placebo granules (0.05<p<0.1) but similar amounts of digoxin were recovered by 24 hours in urine samples. A significantly lower mean peak penicillin concentration (p<0.01) was obtained on guar gum compared to placebo. There was no difference in time to reach peak penicillin concentration. 24 hour urine samples were not available for penicillin. Watanabe et al 1992 (17) Factors affecting prednisolone release from hydrogels prepared with water soluable dietary fibers, xanthan and locust bean gums Single centre prospective study n/a Assessed the release behavior of prednisolone from hydrogels prepared with xanthan and locust bean gums. Release behavior was analyzed spectrophtometrically using 5mls of hydrogel to quantify amount of prednisolone Solubility and viscosity of the hydrogels were also measured. The amount of released prednisolone decreased with increasing gum concentration. Manrique et al 2014 Crushed Tablets: Does the Administration of Food Vehicles and Thickened Fluids to Aid Medication Swallowing Alter Drug Release? Single centre prospective study Compared 5 commercial thickening agents at 3 thicknesses (mild level - 150, moderate level - 400, extremely thick level - 900) by assessing their effect on the dissolution of atenolol in 900mls of pH 1.2 simulated gastric fluid without enzymes (USP dissolution test apparatus II was used). (Also tested other crushed medicines and whole tablets with various different drinks they may be taken with) At thickness level 150 non-significant delay in the dissolution of atenolol was observed At 400 there was variability in brands in the dissolution At 900 all thickened fluids retarded dissolution when compared to whole or crushed tablets in water (even at 3 hours – total duration of experiment). Tomita et al 2015 Effect of food thickener on disintegration and dissolution of magnesium oxide tablets Single centre prospective study Patients who were admitted in hospital wards during 1-15 October 2014 and were taking magnesium oxide (n=147) In vitro experiment – rate of dissolution of magnesium oxide tablet was compared in two different thickeners (xanthan gum and guar gum) each at three different concentrations. Tablets were immersed for 30 minutes and dissolution rate was compared to control. 21 patients were observed to be using thickening agents. Whether they disintegrated it in a small amount of water prior to thickener was observed (15/21). The dose taken was observed. Whether they took an additional laxative was observed. The dissolution rates for immersed tablets were lower than for non-immersed tablets. Concentration of thickener differentially affects dissolution rate. Composition of thickener differentially affects dissolution rate. The mean magnesium dosage was 1705mg/day in those who took it with a thickened fluid without disintegrating it first, 1122mg/day in those who disintegrated then took it with thickened fluid, and 1380 mg/day in those who took it with thin fluids. 31 out of 126 (25%) patients who didn't use thickeners used an additional laxative, while 2 out of 6 (33%) who took magnesium with thickened fluids without disintegration, and 9 out of 15 (60%) of those who took magnesium with thickened fluids after disintegration used another laxative in addition to magnesium. [5] Manrique et al 2016 (18) Oral medication delivery in impaired swallowing: thickening liquid medications for safe swallowing alters dissolution characteristics Single centre prospective study n/a Assesses the effect of thickener on the dissolution of paracetamol using Hitachi U-1900 spectrometer Rheology of thickened samples was assessed including viscosity and yield stress Thickener significantly impacts dissolution of paracetamol The weak gel nature, viscoelasticity and high yield stress impact drug release Tomita et al 2016 Effects of food thickeners on the inhibitory effect of voglibose oral-disintegrating tablets on post-prandial elevation of blood sugar levels Single centre prospective cross over design study N=9 Participants were fasted for 10 hours. Control and study drugs were given 7 days apart. Study drug was volgibose tablet that had been immersed in 3% thickening agent for 10 minutes (the control drug was not immersed). Participants were administered 100g sucrose. Blood glucose levels were checked between 0 and 120 minutes. There was a significant difference in blood glucose levels (p0.01) between taking the immersed tablet Vs control. The difference was highest at 105 minutes after taking the sucrose solution. The blood glucose tablets after taking the immersed tablet were 106.2mg/dL Vs 90.8mg/dL for control. Tomita et al 2017 Effect of food thickener on the inhibitory effect of mitiglinide tablets on post-prandial elevation of blood glucose levels Single centre prospective study. Cross over study design. N = 5 Xanthan gum as thickening agent. Compared disintegration rates with / without emersion in thickener for 1 / 10 minutes. Compared effect of mitiglinide tab / mitiglinide tab emersed in xanthan gum thickening agent on blood glucose levels after digestion of 75g glucose. Significant difference in blood glucose levels from administration to 90 minutes. The greatest difference in blood glucose levels is at 60 minutes (123mg/dL for emersed tablets Vs 82mg/dL for non-emersed tablets. P<0.01). Tomita et al 2018 Effect of xanthan gum as a thickener in widely-used food thickeners on the disintegration of rapidly-disintegrating tablets Single centre prospective study. Four different concentrations of xanthine gums aqueous solutions (0.2% w/v, 0.4% w/v, 0.6% w/v. 0.8% w/v). Magnesium oxide tablets were immersed in four different %w/v xanthan gum aqueous solutions for up to 1, 5 and 10 minutes. Following this their disintegration rates were tested in purified water (In accordance with the described method in Japanese Pharmacopoeia). Magnesium Oxide tablets that had been immersed in higher concentrations (0.6 or 0.8% w/v) of thickener took longer to disintegrate in water. Tomita et al 2019 Effect of food thickener and jelly water on the pharmacokinetics of levofloxacin orally disintegrated tablets Single centre prospective study. Cross over study design N = 4 Disintegration rates after emersion in thickener / jelly water were compared to control. Dissolution rates (after emersion in thickener / jelly water Vs control) in various fluids (at different pH) were compared Compared time taken to reach maximum systemic levofloxacin concentration after emersion in thickener / jelly water (Vs control) Emersion in thickener significantly effects disintegration and dissolution rates No significant difference in time taken to maximum systemic concentration. No significant difference in maximum systemic concentration Takahashi et al 2020 Effect of xanthan gun based food thickeners on the dissolution profile of fluoroquinolones oral formulations Single centre prospective study 3 antibiotics were evaluated Compared the 15 minute dissolution rate with that of non-immersed formulations (control). Floroquinolone film coated tablets were mixed with starch based food thickeners, guar gum based food thickeners of xanthan gum based food thickeners to observe their appearance. The dissolution profile of levofloxacin film coated tablets was not affected by xanthan gum based food thickener (XG- FT). The dissolution of tosufloxacin and ciprofloxacin was delayed after emersion in XG-FT Ciprofloxacin film coated tablets, after emersion in XG-FT / guar gum FT produced a gel like precipitate Matsuo et al 2020 Appropriate usage of food thickening agents to prevent non-disintegration of magnesium oxide tablets Single centre prospective study 1 medication (magnesium oxide, 5 different brands). 2 thickeners (xanthan gum, guar gum) Tablets were immersed in food thickener for 1, 10 and 30 minutes. Tablets stored for different durations at the same temp and humidity Disintegration test performed according to the Japanese Pharacopia (17 edition) Duration immersed in thickener significantly affects disintegration time. Moisture absorbed by magnesium tablets caused a significant delay in their disintegration in water Matsuo et al 2020 Effects of thickened drinks on the disintegration of various oral tablets Single centre prospective study 40 tablets Tablets were immersed in thickener for 1 minute. The disintegration time for non-immersed tablets was used as the control. The disintegration time was defined as the time at which the contents of the tablets were released. Tablets were grouped into naked tablets, film coated tablets, orally disintegrating tablets and enteric and sugar coated tablets. The disintegration time of all orally disintegrating tablets was longer when immersed in thickener than that of non-immersed tablets (but it was less than 2 minutes for the majority of tablets) The disintegration time for several other tablets was shorter or unchanged. Ruis-Picazo et al 2020 Effect of thickener on disintegration, dissolution and permeability of common drug products for elderly patients Single centre prospective study Six medicines (Aspirin, Atenolol, Candesartan, Ramipril, Acenocumarol, Valsartan). The six medicines had their disintegration rates tested (both with and without thickener) The dissolution rates of three medications were tested in fluid at various pH levels (both with and without thickener) – those where thickener had the most marked effect on disintegration time (atenolol, candesartan and valsartan). Permeability through rate intestine was also investigated however animal studies are not being reviewed in this article The disintegration rate increases for all medications with the addition of thickener Thickener did not impact the dissolution rate of atenolol at acidic pH but marked affect on dissolution was observed at pH 4.5 and 6.8. In the case of candesartan thickener slowed dissolution rates at all pH levels tested. Similar results were observed for valsartan with the exception of pH 1.2. Note only minor effects of thickener were observed on dissolution rates at all pH levels when valsartan tablets were crushed. Matsuo et al 2021 Comparison of the effects on tablet disintegration of solvents used to dissolve food thickeners Single centre prospective study 4 medications were assessed (magnesium, senna, furosemide and aspirin) in 12 different solvents (including water, tea, juice and coffee) Xanthan gum-based food thickener was added to each solvent and mixed. Line spread test and the pH of the different solvent thickener mixes were taken. Additionally, tablets were immersed in thickener for one minute and disintegration times were recorded. The disintegration time for magnesium tablets immersed in thickener for 30 minutes was also recorded. Disintegration times of the tablets immersed in thickener for one minute were similar. Magnesium tablets immersed in thickener for 30 minutes had delayed disintegration times. In coffee the disintegration time was 30 minutes, in all other solvents it was over 60 minutes. Different solvents did not differentially affect disintegration rates Bravo-Jose et al 2022 Combining Liquid Oral Drugs with Thickener: Compatibility and Changes in Viscosity Single centre prospective study 45 medicines. The solubility of 45 medicines in thickened fluid were assessed. The amount of thickener added to drugs to achieve various different thickness consistencies was also evaluated. 3 drugs (almagate, ibuprofen and macrogol) were physically incompatible with thickener. Viscosity measurements indicated that different amounts of thickener needed to be added to different drugs. The in vitro studies mostly evaluated the disintegration and dissolution times of various medicines, comparing control medicines to medicines that had been immersed in thickened fluid for various periods of time. The number of medicines studies ranged from 1 to 45. End points in the in vivo experiments included serum / urine concentrations of medication and therapeutic effect (e.g., serum blood glucose levels when evaluating the effect of thickener on diabetic medications). The differential effects of type of thickener in vitro In 2014 Manrique et al [8] compared 5 commercial thickening agents at 3 thicknesses (mild level, moderate level and extremely thick level) by assessing their effect on the dissolution of atenolol. At ‘mild’ thickness level no significant delay in the dissolution of atenolol was observed compared to control. At ‘moderate thickness’ there was variability between brands on dissolution rate and products based on xanthan gum were noted to delay dissolution. Extremely thickened fluids retarded dissolution rates [8]. In 2020 Takahashi compared fluoroquinolone film coated tablets mixed with starch-based food thickener and xanthan gum-based food thickener – finding that starch-based thickener resulted in a more ‘evenly dispersed’ product [9]. Matsuo’s study in 2020 (ref) also bore out the differential between thickeners by comparing guar gum to xanthan gum finding that emersion in guar gum increased disintegration time of magnesium oxide tablets although the study was powered to compare thickeners to the control making the significance unclear. Furthermore, this difference was only noted in some, but not all brands, of magnesium oxide tablets [10]. The differential effects of thickened fluid viscosity In 2018 Tomita found that magnesium oxide tablets that had been immersed in higher concentrations (0.6 or 0.8% w/v) of xanthan gum thickener took longer to disintegrate in water compared to tablets immersed in 0.2 and 0.4% w/v [11]. The effect of thickener concentration was also demonstrated in Manrique’s study in 2014 (as noted above) [8]. The effect of the duration of time emersed in thickened fluid Tomita’s study in 2017 demonstrated that Glufast tablets immersed in xanthan-gum thickener for 1 minute had a shorter disintegration time compared to tablets immersed in thickener for 10 minutes however the significance of this was unclear as the study was powered to compare both groups to the control (i.e., not immersed in thickener) [12]. In 2018 the same group once again demonstrated this principle, this time with magnesium oxide tablets. They found that tablets immersed in 0.6% thickener for 10 minutes had a significantly longer dissolution time than those immersed for 5 minutes. Similar results were born out for tablets immersed in 0.8% thickener [11]. In 2020 Matsuo’s group noted that immersion of magnesium oxide tablets for 10 and 30 minutes in xanthan and guar-gum based food thickening agents caused disintegration delay and non-disintegration, however tablets immersed for 1 minute only quickly disintegrated [10]. In 2021 when the group were comparing the effect of different solvents, they found that magnesium tablets immersed in thickener for 30 minutes had delayed disintegration times compared to 1 minute [13]. The differential effect of thickening different types of liquids Ruis-Picazo’s study in 2020 compared the dissolution rates of medications including atenolol, candesartan and valsartan. They investigated whether the pH of thickened fluid affected the dissolution rate. They found that thickener did not impact the dissolution rate of atenolol at pH1.2 but had a marked effect on dissolution rate observed at pH 4.5 and 6.8 compared to control. In the case of candesartan, thickener slowed dissolution rates at all pH levels tested. Similar results were observed for valsartan with the exception of pH 1.2 [14]. Matsuo’s study in 2020 showed that sports drinks (pH 3.8) and apple flavoured thickened drinks (pH 3.5) had less of an effect on the disintegration time of tablets than roasted green tea (pH 6.5) and green tea flavoured thickened drinks (pH 6.6) [15]. Conversely in 2021 Matsuo compared the disintegration times of 4 medications (magnesium, senna, furosemide and aspirin) in 12 different solvents (including water, tea, juice and coffee) and concluded that different solvents did not differentially affect disintegration rates [13]. The differential effect of thickened fluid on various medications In 2020 Matsuo’s group investigated the disintegration time of 40 different tablets comparing non-immersed tablets to those immersed in 1% xanthan gum-based thickener, 3% xanthan gum-based thickener and a commercially available thickened drink for 1 minute. They found that the medication being tested did differentially impact the effect of thickener on the disintegration rate [11]. It was not clear whether a particular property of some tablets contributed to this. Brave-Jose’s observational study in 2022 bore out similar results. They investigated 45 medicinal products and used a starch-based thickener. They found that some drugs were incompatible with thickener and observed the formation of clumps that did not dissolve. Specifically, they noted this for almagate, ibuprofen and macrogol [16]. The effect of thickener on the therapeutic efficacy of some medications In the first study of its kind, in 1984, Huupponen et al conducted a double-blind study where by volunteers received either digoxin or penicillin medication taken with either guar gum or a placebo preparation (wheat germ) mixed with water [17]. Serum and urine concentrations of digoxin were measured by radioimmunoassay. Serum penicillin concentrations were measured microbiologically according to Reeves et al (1978). They found that the mean peak digoxin concentration was lower when the medication was taken with guar gum compared to placebo granules (0.05<p<0.1) but similar amounts of digoxin were recovered by 24 hours in urine samples. A significantly lower mean peak penicillin concentration (p<0.01) was obtained on guar gum compared to placebo. There was no difference in time to reach peak penicillin concentration. 24-hour urine samples were not available for penicillin. It should be noted, however, that in this study guar gum was not being considered for its properties as a thickening agent (moreover as a treatment for diabetes) and thus it is not clear if the viscosity of the guar gum is similar to what is used in clinical practice for thickening. Furthermore, this was a small study (n=10) only looking at two medications. In 2015 Tomita et al conducted an observational study on patients who were admitted in hospital wards during a 14-day period – who were all taking magnesium oxide (n=147). They found that 21 patients were observed to be using thickening agents. Whether they disintegrated magnesium oxide into a small amount of water prior to adding thickener was observed, and the dose taken was observed. Whether they took additional laxatives was also observed. The mean dose of magnesium was 1705mg/day in those who took a thickened fluid without disintegrating it first, 1122mg/day in those who disintegrated into water and then added thickener. The average dose in those who took it with thin fluids was 1380mg/day. 25% of patients who did not use thickener took an additional laxative. 33% who took magnesium with thickened fluids without disintegration, and 60% of those who took magnesium with thickened fluids after disintegration, used another laxative [18]. This study did not qualify whether thickener significantly affected the amount of magnesium used, or whether there was a statistically significant difference in the requirement for a second laxative. It is also not clear whether other clinical conditions that may have affected laxative use were accounted for. In 2017 Tomita et al performed a single centre prospective cross over study they compared the effect of immersion in xanthan gum Vs control on the therapeutic effect of mitglinide tablets (N=5). They found a significant difference in blood glucose levels from administration to 90 minutes. The greatest difference in blood glucose levels was at 60 minutes (123mg/dL for immersed tablets Vs 82g/dL for non-immersed tablets. P<0.01) [12]. This study corroborated findings from one the group did in 2016 assessing whether immersion in thickener impacted the therapeutic efficacy of another diabetic medication (voglibose) which once again demonstrated a significant difference in blood glucose levels between control and test group (immersed in 3% thickener for 10 minutes, N=9) [19]. Interestingly in 2019 Tomita’s group demonstrated, like in vitro, the in vivo effects of immersion in thickener may differentially affect the therapeutic efficacy of different medications. In a single centre cross over design study, they compared the time taken to reach maximum systemic concentration of levofloxacin after emersion of tablets in thickener, jelly water and control. They found no significant difference in time taken to maximum system concentration and no significant difference in maximum systemic concentration [20]. Discussion There is an expanding field of in-vitro and in-vivo studies evaluating the potential therapeutic impact of thickeners on the medications that they are taken with. Variables such as the type of thickener (starch based, xanthan gum based or guar gum based), the viscosity of the thickened fluid and the duration tablets are immersed in thickener seem relevant. Several in-vitro studies have demonstrated that these variables significantly affect outcome measures including disintegration and dissolution rates. Whether these variables would significantly impact therapeutic outcomes in-vivo remains to be seen, although two out of three single centre studies have demonstrated that the general concept of immersion in thickener does affect therapeutic outcomes [12, 19]. It should be noted however that all participants in these studies were healthy and so what the therapeutic impact on glycaemic control in a diabetic patient taking either mitglinide or voglibose with thickener in the long term remains to be seen. The type of liquid used with thickener has demonstrated differing significance in various studies in vitro. Given the variation of outcomes in these experiments, and the potential clinical relevance (noting changing pH through the digestive tract) further investigation in this field may prove relevant. It may aid understanding of both the significance of the type of liquid that thickener is added to and the relationship between in-vitro and in-vivo experiments – where pH of the liquid used is recorded and is comparable to that of the digestive tract. It may also be important to consider whether enzymes within the digestive tract are significant in terms of whether thickener effects therapeutic outcomes. Both in-vitro and in-vivo studies seem to show that medications (and their therapeutic effect) may be differently affected by the use of thickener. Two in-vitro studies each reviewing 40+ medications have shown that immersion in thickener differentially effects disintegration rates and that several medicines form clumps that do not dissolve when immersed in thickener [15, 16]. The differential effect of medication choice on whether therapeutic impact is likely to be affected by thickener in vivo is also borne out by comparing the studies of Tomita et al [12, 19 and 20]. They demonstrated in two small single centre studies that the therapeutic effect of two diabetes medications is impacted by immersion of tablets in thickener, whereas the systemic concentration of the antibiotic levofloxacin (and thus assumedly it’s therapeutic impact) is not affected. Analogous to the studies reviewed here Wright et al investigated the effect of a novel gel based swallowing aid on systemic salicylate levels and platelet function when delivered with 300mg aspirin tablets in a cross over study of twelve healthy volunteers. This gel formation had been developed to ease the administration of tablets to patients with dysphagia. They found that when aspirin tablets were administered with the gel formation systemic salicylate levels were reduced and platelet function was increased. They concluded that bioequivalence could not be assumed [24]. Although not the focus of this review, the shared properties between this gel based swallowing aid and thickener should be considered (e.g. viscosity). A limitation of this review is that the initial search used only two databases. Search terms included: dysphagia AND bioavailability OR absorption of medicines OR pharmacokinetics AND (with either) Parkinson’s / antibiotic / epilepsy / antiviral / thickened diet (EMBASE only). This was with a view to targeting our review to medicines where by bioavailability is critical to efficacy. During the initial screening of titles / abstracts it became apparent that research into the effect of thickener on the bioavailability of oral medications is a small field and as such we did not exclude any studies based on oral medications being tested. To conclude, these initial small single centre studies suggest that thickener may affect they therapeutic efficacy of at least some medications. The overall clinical relevance of this remains to be seen but may be of particular significance when considering medications such as warfarin, digoxin and some anti-epileptic medications and antibiotics (with narrow therapeutic drug levels). Further larger scale studies are required to evaluate what the therapeutic impact of thickener is on a much bigger range of medications, factoring in other variables that have been shown to be relevant in vitro including type of thickener, viscosity of thickener and duration of immersion. In the mean-time this review highlights the importance of doctors and speech and language therapists to consider carefully the necessity of oral thickener and the route of prescribed medications Declarations Statements and Declarations: The authors have no direct or indirect financial or non-financial interests relating to the submitted work. References More harm than good – Why more isn’t always better with older people’s medicines. Age UK. 2019. L. Petchey and T. Gentry Pathophysiology, Relevance and Natural History of Oropharyngeal Dysphagia among Older People. Nestle Nutrition Institute workshop series. 2012. 57-66 P .Clave, L. Rofes, S. Carrion, O. Ortegra, M. Cabre, M. Serra-Prat and V. Arreola Use of thickened liquids in skilled nursing facilities. Journal of the American Dietetic Association. 2004. 104 (8) 1222-6 V.Castellanos, E. Butler, L. Gluch and B. Burke Use of modified diets to prevent aspiration in oropharyngeal dysphagia: is current practice justified? BMC Geriatrics. O’Keeffee. 2018. 18: 167 The influence of food texture and liquid consistency modification on swallowing physiology and function: a systematic review. Dysphagia. 2015. 2-26. C. Steele, W. Alsanei, S. Ayanikalath, C. Barbon, J. Chen, J. Chichero, K. Coutts, R. Dantas, J. Duivestein, L. Giosa, B. Hanson, P. Lam, C. Lecko, C. Leigh, A. Nagy, A. Namasivayam, W. Nascimento, I. Odendaal, C. Smith and H. Wang Development of international terminology and definitions for texture modified foods and thickened fluids used in dysphagia management: the IDDSI frame work. Dysphagia. 2016. 293-314. J. Cichero, P. Lam, C. Steele, B. Hanson, J. Chen, R. Dantas, J. Duivestein, J. Kayashita, C. Lecko, J. Murray, M. Pillay, L. Riquelme and S. Sanschus Preferred reporting items for systematic review and meta-analysis protocols (PRIMA-P) 2015: elaboration and explanation. British Medical Journal. 2015 1-25 L.Shamseer, D. Moher, M. Clarke, D. Ghersi, A. Liberati, M. Petticrew, P. Shekelle, and L. Stewart Crushed Tablets: Does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release? Journal of pharmacology and pharmaceutical sciences. 2014. 17(2) 207-219 Y. Manrique, D. Lee, F. Islam, L. Nissen, J. Cichero, J. Stokes and K. Steadman Effect of xanthan gum-based food thickeners on the dissolution profile of fluoroquinolones oral formulations. Journal of pharmaceutical health-care and sciences 2020 30(6) N. Takahashi, Y. Fujita, N. Takahashi, A. Nakamura and T. Harada Appropriate usage of food thickening agents to prevent non-disintegration of magnesium oxide tablets. Nature scientific reports. 2020 10(16089) T. Matsuo, A. Sato, K. Kudo, Y. Sadzuka and T. Tomita Effect of xanthan gum as a thickener in widely-used food thickeners on the disintegration of rapidly disintegrating tablets. Japanese Journal of comprehensive rehabilitation science. 2018. (9) 22-28 T. Tomita, T. Fukui, S. Takanohahsi, H. Goto, T. Yoshida K. Sumiya, Y. Kohda and K. Kudo Effect of food thickener on the inhibitory effect of mitiglinide tablets on post-prandial elevation of blood glucose levels. Dysphagia. 2017. 32(3) 449-453 T. Tomita, H. Goto, K. Sumiya, T. Yoshida, K. Tanaka, K. Kudo and Y. Kohda Comparison of the effects on tablets disintegration of solvents used to dissolve food thickeners. Journal of texture studies. 2021 52(3) 380-388 T. Matsuo, H. Sasaki, T. Tomita and Y. Sadzuka Effect of thickener on disintegration, dissolution and permeability of common drug products for elderly patients. European journal of pharmaceutics and biopharmaceutics. 2020. 153. 168-176. A.Ruiz-Picazo, S. Colon-Useche, M. Gonzalez-Alvarez, I. Gonzalez-Alvarez, M. Bermejo and P. Langguth Effects of thickened drinks on the disintegration of various oral tablets. Heliyon. 2020. 6(12). T. Matsuo, C. Sato, T. Tomita and Y. Sadzuka Combining liquid oral drugs with thickener: compatibility and changes in viscosity. Dysphagia. 2022. 37 889-899 P. Bravo-Jose, C. Saez-Lleo and E. Moreno-Guillamont Effect of guar gum, a fibre preparation, on digoxin and penicillin absorption in man. European journal of clinical pharmacology. 1984. 26(2) 279-281. R. Huupponen, P. Seppala and E. Lisalo Effect of food thickener on disintegration and dissolution of magnesium oxide tablets. Journal of the pharmaceutical society of Japan. 2015. 135(6) 835-840. T. Tomita, H. Goto, Y. Yoshimura, Y. Tsubouchi, R. Nakanishi, C. Kojima, M. Yoneshima, T. Yoshida, K. Tanaka, K. Sumiya and Y. Kohda Effect of food thickeners on the inhibitory effect of voglibose oral-disintegrating tablets on post-prandial elevation of blood sugar levels. Journal of pharmaceutical society of Japan. 2016. 136(8) 1171-1176. T. Tomita, H. Goto, K. Sumiya, T. Yoshida, K. Tanaka and Y. Kohda Effect of food thickener and jelly water on the pharmacokinetics of levofloxacin orally disintegrating tablets. Heliyon. 2019. 26;5(11). T. Tomita, A. Yamaguchi, N. Nishimura, H. Goto, K. Sumiya, R. Arakawa, T. Yoshida, H. Tachiki, Y. Kohda and K. Kudo Factors affecting prednisolone release from hydrogels prepared with water soluble dietary fibres, xanthan and locust bean gums. Chemical and pharmaceutical bulletin. 1992. 40(2) 459-462. K. Watanabe, S. Yakou, K. Takayama, Y. Machida and T. Nagai Oral medication delivery in impaired swallowing: thickening liquid medications for safe swallowing alters dissolution characteristics. Drug development and industrial pharmacy. 2016. 42(9) 1537-1544. Y. Manrique, A. Sparkes, J. Chichero, J. Stokes, L. Nissen and K. Steadman Dysphagia in older adults. Mayo Clinic Proceedings. 2021. 96(2) 488 – 497 Administration of aspirin tablets using a novel gel-based swallowing aid: An open label randomised controlled cross over trial. BMJ innovations. 2019 113-119 D. Wright, J. Potter, A. Clark, A. Blyth, V. Maskrey, G. Mencarelli, S. Wicks and D. Craig Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Minor revisions 13 Sep, 2023 Reviewers agreed at journal 09 Aug, 2023 Reviewers invited by journal 01 Aug, 2023 Editor assigned by journal 31 Jul, 2023 First submitted to journal 30 Jul, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3199117","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":223159235,"identity":"5cdeba32-3be7-4c02-9f91-1dfa79586738","order_by":0,"name":"Jayne Atkin","email":"","orcid":"","institution":"King's College Hospital NHS Trust: King's College Hospital NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Jayne","middleName":"","lastName":"Atkin","suffix":""},{"id":223159236,"identity":"944f3175-d86b-49c9-ab72-fd4015ccc74a","order_by":1,"name":"Christopher Devaney","email":"data:image/png;base64,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","orcid":"https://orcid.org/0009-0002-6692-7290","institution":"Lewisham and Greenwich NHS Trust","correspondingAuthor":true,"prefix":"","firstName":"Christopher","middleName":"","lastName":"Devaney","suffix":""},{"id":223159237,"identity":"84f9cff6-4a84-40c4-9d60-60be86c1c9e5","order_by":2,"name":"Yuki Yoshimatsu","email":"","orcid":"","institution":"Lewisham and Greenwich NHS Trust","correspondingAuthor":false,"prefix":"","firstName":"Yuki","middleName":"","lastName":"Yoshimatsu","suffix":""},{"id":223159238,"identity":"93a84864-c0a1-48fa-a1d2-d9a6c8894bf5","order_by":3,"name":"David Smithard","email":"","orcid":"","institution":"Lewisham and Greenwich NHS Trust","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Smithard","suffix":""}],"badges":[],"createdAt":"2023-07-24 11:04:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3199117/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3199117/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":41191655,"identity":"a20988e4-3913-4cf5-ad13-6ac5d778b5a7","added_by":"auto","created_at":"2023-08-07 15:59:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":50552,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow diagram outlining research methodology\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3199117/v1/5b8ffb8084779188ba515765.png"},{"id":41191689,"identity":"a3e5d9fc-569a-4cab-b2ed-63468589065f","added_by":"auto","created_at":"2023-08-07 15:59:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":335422,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3199117/v1/177766a7-e054-42b8-8b93-a4fca40b4b11.pdf"}],"financialInterests":"","formattedTitle":"Modified Diets and Medication in Dysphagia – The effect of thickener on drug bioavailability: A systematic review","fulltext":[{"header":"Key Summary Points","content":"\u003cp\u003eAim: to understand further the effect of thickener on medications and their pharmacokinetic and therapeutic profiles, using a literature search.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFindings:\u0026nbsp;Despite dysphagia and polypharmacy being common in older adults, little is known about the effects of altering liquid viscosity on the pharmacokinetics and therapeutic effect of most medications.\u003c/p\u003e\n\u003cp\u003eMessage: further work must be undertaken to support clinicians, pharmacists and patients in understanding the effects of thickener.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eIn England more than 1 in 10 people over 65 years take at least eight different prescribed medications each week. This increases as people get older \u0026ndash; to nearly 1 in 4 in the over 85\u0026rsquo;s [1].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDysphagia is a geriatric syndrome associated with many common long-term clinical conditions including stroke, dementia, Parkinson\u0026rsquo;s disease and frailty. Clave et al report that oropharyngeal dysphagia may affect 30 to 40% of the population aged 65 years or more. They also report that dysphagia affects more than 50% of people living in nursing homes [2]. Castellanos et al found that 8.3% of residents in nursing home facilities received thickened fluids [3]. Thickening fluids is an increasingly used strategy to reduce the risk of aspiration. The increased viscosity of fluids compensates for a swallowing deficit by slowing down the flow of the fluid from the mouth to the oropharynx \u0026ndash; allowing time for glottis closure [4]. Steele et al performed a systematic review on the effect of food texture and liquid consistency modification on swallowing physiology and function, they concluded that there is a clear reduction in the risk of aspiration as liquids progress from thin to very thick (studies involving barium swallow under video fluoroscopy in adults with dysphagia) [5].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGiven the overlapping profiles of those patients prescribed multiple medications and those receiving thickened fluids, understanding the interactions between thickened fluids and medications and how this may affect medication bioavailability and therapeutic effect is essential.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThickening agents can be broadly classified into 3 groups: starch based, guar gum based and xanthan gum based, often chosen based on their cost, availability, consistency and flavour. There is variability in how thick fluids are that patients receive. In 2012 the international dysphagia diet standardisation initiative was founded and the characteristics of fluids, thickened fluids and foods were described. The level of viscosity of fluids ranges from 0 (thin) to 4 (extremely thick) [6].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere have been a few studies reporting the effect of thickeners on drugs, but no systematic review has been performed. We have conducted a systematic review to answer the question of whether thickened fluids affect the bioavailability of oral medications. Furthermore, whether the level of thickness of fluids, the type of thickener used and the duration of emersion in thickened fluid affects bioavailability of medications. Additionally, we have reviewed evidence as to whether the bioavailability and therapeutic effect of various medications are differentially affected by thickener.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003ePRISMA methodology was followed to structure the review [7] (see Fig.\u0026nbsp;1). An experienced librarian performed a literature search of MEDLINE and EMBASE. Search terms included: dysphagia AND bioavailability OR absorption of medicines OR pharmacokinetics AND (with either) Parkinson\u0026rsquo;s / antibiotic / epilepsy / antiviral / thickened diet (EMBASE only). Two of the authors screened search results (titles and abstracts, duplicates were removed at this stage). No software was used in this process. The terms \u0026lsquo;Parkinson\u0026rsquo;s\u0026rsquo;, \u0026lsquo;antibiotic\u0026rsquo; \u0026lsquo;epilepsy\u0026rsquo; and \u0026lsquo;antiviral\u0026rsquo; were included so that we could focus our search on time critical medications and medications that have a critical impact on clinical outcomes. However, when evaluating search results, we have included all medications due to the small number of studies in this field. We excluded unrelated articles, review articles and conference abstracts. We also excluded animal studies and articles relating to nasogastric / percutaneous endoscopic gastrostomy feeds. All articles included were peer reviewed published articles. All ages over 18 years were included in both community and hospital settings. No articles were excluded based on type of medication. Articles describing in vitro experiments were also included. Articles selected for a full review were selected independently and then agreed by both authors. Reference lists from these articles were reviewed and further relevant articles were identified. There was no discrepancy in selected articles. All relevant articles were then summarised according to study design, number of participants, method and main conclusions.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e526 results were found on the initial search. A further 15 articles were identified by the authors following reviews of reference lists. Following review of the abstracts (performed independently by 2 of the authors) 508 publications were rejected. 33 received a full text review and a further 18 were rejected, with the remaining 15 articles included in the review. All studies reviewed were small single centre studies. The rationale for rejecting studies included study design (e.g., animal studies), study type (e.g., review articles and conference abstracts).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFifteen papers published between 1984 and 2021 were reviewed (outlined in table 1). Five studies were in vivo and the remaining 10 studies were in vitro.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 1: Summary of articles included for review\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cdiv align=\"right\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eAuthor, Year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eTitle\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eStudy Design\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eParticipants\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eMethod\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eMain Conclusions\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHuupponen et al 1984\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eEffect of Guar Gum, a Fibre Preparation, on Digoxin and Penicillin Absorption in Man\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eDouble blind study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eN = 10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eVolunteers received either digoxin or penicillin, medication was taken with either guar gum or a placebo preparation (wheat germ) mixed with 200mls of water.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSerum and urine concentrations of digoxin were measured by radioimmunoassay.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSerum penicillin concentrations were measured microbiologically according to Reeves et at (1978)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eMean peak digoxin concentration was lower after guar gum than after placebo granules (0.05\u0026lt;p\u0026lt;0.1) but similar amounts of digoxin were recovered by 24 hours in urine samples.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eA significantly lower mean peak penicillin concentration (p\u0026lt;0.01) was obtained on guar gum compared to placebo. There was no difference in time to reach peak penicillin concentration. 24 hour urine samples were not available for penicillin.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eWatanabe et al 1992 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eFactors affecting prednisolone release from hydrogels prepared with water soluable dietary fibers, xanthan and locust bean gums\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Single centre prospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eAssessed the release behavior of prednisolone from hydrogels prepared with xanthan and locust bean gums.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRelease behavior was analyzed spectrophtometrically using 5mls of hydrogel to quantify amount of prednisolone\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSolubility and viscosity of the hydrogels were also measured.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eThe amount of released prednisolone decreased with increasing gum concentration.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eManrique et al 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eCrushed Tablets: Does the Administration of Food Vehicles and Thickened Fluids to Aid Medication Swallowing Alter Drug Release?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eCompared 5 commercial thickening agents at 3 thicknesses (mild level - 150, moderate level - 400, extremely thick level - 900) by assessing their effect on the dissolution of atenolol in 900mls of pH 1.2 simulated gastric fluid without enzymes (USP dissolution test apparatus II was used).\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(Also tested other crushed medicines and whole tablets with various different drinks they may be taken with)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;At thickness level 150 non-significant delay in the dissolution of atenolol was observed\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAt 400 there was variability in brands in the dissolution\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAt 900 all thickened fluids retarded dissolution when compared to whole or crushed tablets in water (even at 3 hours \u0026ndash; total duration of experiment).\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eTomita et al 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eEffect of food thickener on disintegration and dissolution of magnesium oxide tablets\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective study\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003ePatients who were admitted in hospital wards during 1-15 October 2014 and were taking magnesium oxide (n=147)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eIn vitro experiment \u0026ndash; rate of dissolution of magnesium oxide tablet was compared in two different thickeners (xanthan gum and guar gum) each at three different concentrations. Tablets were immersed for 30 minutes and dissolution rate was compared to control.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 patients were observed to be using thickening agents. Whether they disintegrated it in a small amount of water prior to thickener was observed (15/21). The dose taken was observed. Whether they took an additional laxative was observed.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eThe dissolution rates for immersed tablets were lower than for non-immersed tablets. Concentration of thickener differentially affects dissolution rate. Composition of thickener differentially affects dissolution rate.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe mean magnesium dosage was 1705mg/day in those who took it with a thickened fluid without disintegrating it first, 1122mg/day in those who disintegrated then took it with thickened fluid, and 1380 mg/day in those who took it with thin fluids. 31 out of 126 (25%) patients who didn\u0026apos;t use thickeners used an additional laxative, while 2 out of 6 (33%) who took magnesium with thickened fluids without disintegration, and 9 out of 15 (60%) of those who took magnesium with thickened fluids after disintegration used another laxative in addition to magnesium.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e[5] Manrique et al 2016 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eOral medication delivery in impaired swallowing: thickening liquid medications for safe swallowing alters dissolution characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Single centre prospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eAssesses the effect of thickener on the dissolution of paracetamol using Hitachi U-1900 spectrometer\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRheology of thickened samples was assessed including viscosity and yield stress\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eThickener significantly impacts dissolution of paracetamol\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe weak gel nature, viscoelasticity and high yield stress impact drug release\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eTomita et al 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eEffects of food thickeners on the inhibitory effect of voglibose oral-disintegrating tablets on post-prandial elevation of blood sugar levels\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective cross over design study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eN=9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eParticipants were fasted for 10 hours. Control and study drugs were given 7 days apart. Study drug was volgibose tablet that had been immersed in 3% thickening agent for 10 minutes (the control drug was not immersed). Participants were administered 100g sucrose. Blood glucose levels were checked between 0 and 120 minutes.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eThere was a significant difference in blood glucose levels (p0.01) between taking the immersed tablet Vs control. The difference was highest at 105 minutes after taking the sucrose solution. The blood glucose tablets after taking the immersed tablet were 106.2mg/dL Vs 90.8mg/dL for control.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eTomita et al\u003c/p\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eEffect of food thickener on the inhibitory effect of mitiglinide tablets on post-prandial elevation of blood glucose levels\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective study. Cross over study design.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eN = 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eXanthan gum as thickening agent. Compared disintegration rates with / without emersion in thickener for 1 / 10 minutes.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCompared effect of mitiglinide tab / mitiglinide tab emersed in xanthan gum thickening agent on blood glucose levels after digestion of 75g glucose.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eSignificant difference in blood glucose levels from administration to 90 minutes.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe greatest difference in blood glucose levels is at 60 minutes (123mg/dL for emersed tablets Vs 82mg/dL for non-emersed tablets. P\u0026lt;0.01).\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eTomita et al 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eEffect of xanthan gum as a thickener in widely-used food thickeners on the disintegration of rapidly-disintegrating tablets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective study.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eFour different concentrations of xanthine gums aqueous solutions (0.2% w/v, 0.4% w/v, 0.6% w/v. 0.8% w/v).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eMagnesium oxide tablets were immersed in four different %w/v xanthan gum aqueous solutions for up to 1, 5 and 10 minutes.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFollowing this their disintegration rates were tested in purified water (In accordance with the described method in\u0026nbsp;Japanese Pharmacopoeia).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eMagnesium Oxide tablets that had been immersed in higher concentrations (0.6 or 0.8% w/v) of thickener took longer to disintegrate in water.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eTomita et al 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eEffect of food thickener and jelly water on the pharmacokinetics of levofloxacin orally disintegrated tablets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective study. Cross over study design\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;N = 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eDisintegration rates after emersion in thickener / jelly water were compared to control.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDissolution rates (after emersion in thickener / jelly water Vs control) in various fluids (at different pH) were compared\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCompared time taken to reach maximum systemic levofloxacin concentration after emersion in thickener / jelly water (Vs control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eEmersion in thickener significantly effects disintegration and dissolution rates\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo significant difference in time taken to maximum systemic concentration.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo significant difference in maximum systemic concentration\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eTakahashi et al 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eEffect of xanthan gun based food thickeners on the dissolution profile of fluoroquinolones oral formulations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e3 antibiotics were evaluated\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eCompared the 15 minute dissolution rate with that of non-immersed formulations (control).\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFloroquinolone film coated tablets were mixed with starch based food thickeners, guar gum based food thickeners of xanthan gum based food thickeners to observe their appearance.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eThe dissolution profile of levofloxacin film coated tablets was not affected by xanthan gum based food thickener (XG- FT).\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;The dissolution of tosufloxacin and ciprofloxacin was delayed after emersion in XG-FT\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCiprofloxacin film coated tablets, after emersion in XG-FT / guar gum FT produced a gel like precipitate\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eMatsuo et al 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eAppropriate usage of food thickening agents to prevent non-disintegration of magnesium oxide tablets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e1 medication (magnesium oxide, 5 different brands). 2 thickeners (xanthan gum, guar gum)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eTablets were immersed in food thickener for 1, 10 and 30 minutes.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eTablets stored for different durations at the same temp and humidity\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDisintegration test performed according to the Japanese Pharacopia (17 edition)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eDuration immersed in thickener significantly affects disintegration time.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMoisture absorbed by magnesium tablets caused a significant delay in their disintegration in water\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eMatsuo et al 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eEffects of thickened drinks on the disintegration of various oral tablets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e40 tablets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eTablets were immersed in thickener for 1 minute. The disintegration time for non-immersed tablets was used as the control. The disintegration time was defined as the time at which the contents of the tablets were released.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eTablets were grouped into naked tablets, film coated tablets, orally disintegrating tablets and enteric and sugar coated tablets.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eThe disintegration time of all orally disintegrating tablets was longer when immersed in thickener than that of non-immersed tablets (but it was less than 2 minutes for the majority of tablets)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe disintegration time for several other tablets was shorter or unchanged.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eRuis-Picazo et al 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eEffect of thickener on disintegration, dissolution and permeability of common drug products for elderly patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eSix medicines (Aspirin, Atenolol, Candesartan, Ramipril, Acenocumarol, Valsartan).\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eThe six medicines had their disintegration rates tested (both with and without thickener)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe dissolution rates of three medications were tested in fluid at various pH levels (both with and without thickener) \u0026ndash; those where thickener had the most marked effect on disintegration time (atenolol, candesartan and valsartan). \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ePermeability through rate intestine was also investigated however animal studies are not being reviewed in this article\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eThe disintegration rate increases for all medications with the addition of thickener\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThickener did not impact the dissolution rate of atenolol at acidic pH but marked affect on dissolution was observed at pH 4.5 and 6.8.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eIn the case of candesartan thickener slowed dissolution rates at all pH levels tested. Similar results were observed for valsartan with the exception of pH 1.2.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNote only minor effects of thickener were observed on dissolution rates at all pH levels when valsartan tablets were crushed.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003eMatsuo et al 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eComparison of the effects on tablet disintegration of solvents used to dissolve food thickeners\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003eSingle centre prospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e4 medications were assessed (magnesium, senna, furosemide and aspirin) in 12 different solvents (including water, tea, juice and coffee)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eXanthan gum-based food thickener was added to each solvent and mixed. Line spread test and the pH of the different solvent thickener mixes were taken.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAdditionally, tablets were immersed in thickener for one minute and disintegration times were recorded.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe disintegration time for magnesium tablets immersed in thickener for 30 minutes was also recorded.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003eDisintegration times of the tablets immersed in thickener for one minute were similar.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMagnesium tablets immersed in thickener for 30 minutes had delayed disintegration times. In coffee the disintegration time was 30 minutes, in all other solvents it was over 60 minutes.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDifferent solvents did not differentially affect disintegration rates\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eBravo-Jose et al 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eCombining Liquid Oral Drugs with Thickener: Compatibility and Changes in Viscosity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Single centre prospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e45 medicines.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eThe solubility of 45 medicines in thickened fluid were assessed.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe amount of thickener added to drugs to achieve various different thickness consistencies was also evaluated.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.742268041237114%\" valign=\"top\"\u003e\n \u003cp\u003e3 drugs (almagate, ibuprofen and macrogol) were physically incompatible with thickener.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eViscosity measurements indicated that different amounts of thickener needed to be added to different drugs.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe in vitro studies mostly evaluated the disintegration and dissolution times of various medicines, comparing control medicines to medicines that had been immersed in thickened fluid for various periods of time. The number of medicines studies ranged from 1 to 45. End points in the in vivo experiments included serum / urine concentrations of medication and therapeutic effect (e.g., serum blood glucose levels when evaluating the effect of thickener on diabetic medications).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe differential effects of type of thickener in vitro\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn 2014 Manrique et al [8] compared 5 commercial thickening agents at 3 thicknesses (mild level, moderate level and extremely thick level) by assessing their effect on the dissolution of atenolol. At \u0026lsquo;mild\u0026rsquo; thickness level no significant delay in the dissolution of atenolol was observed compared to control. At \u0026lsquo;moderate thickness\u0026rsquo; there was variability between brands on dissolution rate and products based on xanthan gum were noted to delay dissolution. Extremely thickened fluids retarded dissolution rates [8]. In 2020 Takahashi compared fluoroquinolone film coated tablets mixed with starch-based food thickener and xanthan gum-based food thickener \u0026ndash; finding that starch-based thickener resulted in a more \u0026lsquo;evenly dispersed\u0026rsquo; product [9]. Matsuo\u0026rsquo;s study in 2020 (ref) also bore out the differential between thickeners by comparing guar gum to xanthan gum finding that emersion in guar gum increased disintegration time of magnesium oxide tablets although the study was powered to compare thickeners to the control making the significance unclear. Furthermore, this difference was only noted in some, but not all brands, of magnesium oxide tablets [10].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe differential effects of thickened fluid viscosity\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn 2018 Tomita found that magnesium oxide tablets that had been immersed in higher concentrations (0.6 or 0.8% w/v) of xanthan gum thickener took longer to disintegrate in water compared to tablets immersed in 0.2 and 0.4% w/v [11]. The effect of thickener concentration was also demonstrated in Manrique\u0026rsquo;s study in 2014 (as noted above) [8].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe effect of the duration of time emersed in thickened fluid\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTomita\u0026rsquo;s study in 2017 demonstrated that Glufast tablets immersed in xanthan-gum thickener for 1 minute had a shorter disintegration time compared to tablets immersed in thickener for 10 minutes however the significance of this was unclear as the study was powered to compare both groups to the control (i.e., not immersed in thickener) [12]. In 2018 the same group once again demonstrated this principle, this time with magnesium oxide tablets. They found that tablets immersed in 0.6% thickener for 10 minutes had a significantly longer dissolution time than those immersed for 5 minutes. Similar results were born out for tablets immersed in 0.8% thickener [11].\u003c/p\u003e\n\u003cp\u003eIn 2020 Matsuo\u0026rsquo;s group noted that immersion of magnesium oxide tablets for 10 and 30 minutes in xanthan and guar-gum based food thickening agents caused disintegration delay and non-disintegration, however tablets immersed for 1 minute only quickly disintegrated [10]. In 2021 when the group were comparing the effect of different solvents, they found that magnesium tablets immersed in thickener for 30 minutes had delayed disintegration times compared to 1 minute [13].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe differential effect of thickening different types of liquids\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRuis-Picazo\u0026rsquo;s study in 2020 compared the dissolution rates of medications including atenolol, candesartan and valsartan. They investigated whether the pH of thickened fluid affected the dissolution rate. They found that thickener did not impact the dissolution rate of atenolol at pH1.2 but had a marked effect on dissolution rate observed at pH 4.5 and 6.8 compared to control. In the case of candesartan, thickener slowed dissolution rates at all pH levels tested. Similar results were observed for valsartan with the exception of pH 1.2 [14]. Matsuo\u0026rsquo;s study in 2020 showed that sports drinks (pH 3.8) and apple flavoured thickened drinks (pH 3.5) had less of an effect on the disintegration time of tablets than roasted green tea (pH 6.5) and green tea flavoured thickened drinks (pH 6.6) [15]. Conversely in 2021 Matsuo compared the disintegration times of 4 medications (magnesium, senna, furosemide and aspirin) in 12 different solvents (including water, tea, juice and coffee) and concluded that different solvents did not differentially affect disintegration rates [13].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe differential effect of thickened fluid on various medications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn 2020 Matsuo\u0026rsquo;s group investigated the disintegration time of 40 different tablets comparing non-immersed tablets to those immersed in 1% xanthan gum-based thickener, 3% xanthan gum-based thickener and a commercially available thickened drink for 1 minute. They found that the medication being tested did differentially impact the effect of thickener on the disintegration rate [11]. It was not clear whether a particular property of some tablets contributed to this. Brave-Jose\u0026rsquo;s observational study in 2022 bore out similar results. They investigated 45 medicinal products and used a starch-based thickener. They found that some drugs were incompatible with thickener and observed the formation of clumps that did not dissolve. Specifically, they noted this for almagate, ibuprofen and macrogol [16].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe effect of thickener on the therapeutic efficacy of some medications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the first study of its kind, in 1984, Huupponen et al conducted a double-blind study where by volunteers received either digoxin or penicillin medication taken with either guar gum or a placebo preparation (wheat germ) mixed with water [17]. Serum and urine concentrations of digoxin were measured by radioimmunoassay. Serum penicillin concentrations were measured microbiologically according to Reeves et al (1978). They found that the mean peak digoxin concentration was lower when the medication was taken with guar gum compared to placebo granules (0.05\u0026lt;p\u0026lt;0.1) but similar amounts of digoxin were recovered by 24 hours in urine samples. A significantly lower mean peak penicillin concentration (p\u0026lt;0.01) was obtained on guar gum compared to placebo. There was no difference in time to reach peak penicillin concentration. 24-hour urine samples were not available for penicillin. It should be noted, however, that in this study guar gum was not being considered for its properties as a thickening agent (moreover as a treatment for diabetes) and thus it is not clear if the viscosity of the guar gum is similar to what is used in clinical practice for thickening. Furthermore, this was a small study (n=10) only looking at two medications.\u003c/p\u003e\n\u003cp\u003eIn 2015 Tomita et al conducted an observational study on patients who were admitted in hospital wards during a 14-day period \u0026ndash; who were all taking magnesium oxide (n=147). They found that 21 patients were observed to be using thickening agents. Whether they disintegrated magnesium oxide into a small amount of water prior to adding thickener was observed, and the dose taken was observed. Whether they took additional laxatives was also observed. The mean dose of magnesium was 1705mg/day in those who took a thickened fluid without disintegrating it first, 1122mg/day in those who disintegrated into water and then added thickener. The average dose in those who took it with thin fluids was 1380mg/day. 25% of patients who did not use thickener took an additional laxative. 33% who took magnesium with thickened fluids without disintegration, and 60% of those who took magnesium with thickened fluids after disintegration, used another laxative [18]. This study did not qualify whether thickener significantly affected the amount of magnesium used, or whether there was a statistically significant difference in the requirement for a second laxative. It is also not clear whether other clinical conditions that may have affected laxative use were accounted for.\u003c/p\u003e\n\u003cp\u003eIn 2017 Tomita et al performed a single centre prospective cross over study they compared the effect of immersion in xanthan gum Vs control on the therapeutic effect of mitglinide tablets (N=5). They found a significant difference in blood glucose levels from administration to 90 minutes. The greatest difference in blood glucose levels was at 60 minutes (123mg/dL for immersed tablets Vs 82g/dL for non-immersed tablets. P\u0026lt;0.01) [12]. This study corroborated findings from one the group did in 2016 assessing whether immersion in thickener impacted the therapeutic efficacy of another diabetic medication (voglibose) which once again demonstrated a significant difference in blood glucose levels between control and test group (immersed in 3% thickener for 10 minutes, N=9) [19].\u003c/p\u003e\n\u003cp\u003eInterestingly in 2019 Tomita\u0026rsquo;s group demonstrated, like in vitro, the in vivo effects of immersion in thickener may differentially affect the therapeutic efficacy of different medications. In a single centre cross over design study, they compared the time taken to reach maximum systemic concentration of levofloxacin after emersion of tablets in thickener, jelly water and control. They found no significant difference in time taken to maximum system concentration and no significant difference in maximum systemic concentration [20].\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThere is an expanding field of in-vitro and in-vivo studies evaluating the potential therapeutic impact of thickeners on the medications that they are taken with. Variables such as the type of thickener (starch based, xanthan gum based or guar gum based), the viscosity of the thickened fluid and the duration tablets are immersed in thickener seem relevant. Several in-vitro studies have demonstrated that these variables significantly affect outcome measures including disintegration and dissolution rates. Whether these variables would significantly impact therapeutic outcomes in-vivo remains to be seen, although two out of three single centre studies have demonstrated that the general concept of immersion in thickener does affect therapeutic outcomes [12, 19]. It should be noted however that all participants in these studies were healthy and so what the therapeutic impact on glycaemic control in a diabetic patient taking either mitglinide or voglibose with thickener in the long term remains to be seen.\u003c/p\u003e\n\u003cp\u003eThe type of liquid used with thickener has demonstrated differing significance in various studies in vitro. Given the variation of outcomes in these experiments, and the potential clinical relevance (noting changing pH through the digestive tract) further investigation in this field may prove relevant. It may aid understanding of both the significance of the type of liquid that thickener is added to and the relationship between in-vitro and in-vivo experiments \u0026ndash; where pH of the liquid used is recorded and is comparable to that of the digestive tract. It may also be important to consider whether enzymes within the digestive tract are significant in terms of whether thickener effects therapeutic outcomes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBoth in-vitro and in-vivo studies seem to show that medications (and their therapeutic effect) may be differently affected by the use of thickener. Two in-vitro studies each reviewing 40+ medications have shown that immersion in thickener differentially effects disintegration rates and that several medicines form clumps that do not dissolve when immersed in thickener [15, 16]. The differential effect of medication choice on whether therapeutic impact is likely to be affected by thickener in vivo is also borne out by comparing the studies of Tomita et al [12, 19 and 20]. They demonstrated in two small single centre studies that the therapeutic effect of two diabetes medications is impacted by immersion of tablets in thickener, whereas the systemic concentration of the antibiotic levofloxacin (and thus assumedly it\u0026rsquo;s therapeutic impact) is not affected.\u003c/p\u003e\n\u003cp\u003eAnalogous to the studies reviewed here Wright et al investigated the effect of a novel gel based swallowing aid on systemic salicylate levels and platelet function when delivered with 300mg aspirin tablets in a cross over study of twelve healthy volunteers. This gel formation had been developed to ease the administration of tablets to patients with dysphagia. They found that when aspirin tablets were administered with the gel formation systemic salicylate levels were reduced and platelet function was increased. They concluded that bioequivalence could not be assumed [24]. Although not the focus of this review, the shared properties between this gel based swallowing aid and thickener should be considered (e.g. viscosity).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA limitation of this review is that the initial search used only two databases. Search terms included: dysphagia AND bioavailability OR absorption of medicines OR pharmacokinetics AND (with either) Parkinson\u0026rsquo;s / antibiotic / epilepsy / antiviral / thickened diet (EMBASE only). This was with a view to targeting our review to medicines where by bioavailability is critical to efficacy. During the initial screening of titles / abstracts it became apparent that research into the effect of thickener on the bioavailability of oral medications is a small field and as such we did not exclude any studies based on oral medications being tested.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo conclude, these initial small single centre studies suggest that thickener may affect they therapeutic efficacy of at least some medications. The overall clinical relevance of this remains to be seen but may be of particular significance when considering medications such as warfarin, digoxin and some anti-epileptic medications and antibiotics (with narrow therapeutic drug levels). Further larger scale studies are required to evaluate what the therapeutic impact of thickener is on a much bigger range of medications, factoring in other variables that have been shown to be relevant in vitro including type of thickener, viscosity of thickener and duration of immersion. In the mean-time this review highlights the importance of doctors and speech and language therapists to consider carefully the necessity of oral thickener and the route of prescribed medications\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatements and Declarations:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no direct or indirect financial or non-financial interests relating to the submitted work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eMore harm than good \u0026ndash; Why more isn\u0026rsquo;t always better with older people\u0026rsquo;s medicines. Age UK. 2019. L. Petchey and T. Gentry\u003c/li\u003e\n \u003cli\u003ePathophysiology, Relevance and Natural History of Oropharyngeal Dysphagia among Older People. Nestle Nutrition Institute workshop series. 2012. 57-66 P .Clave, L. Rofes, S. Carrion, O. Ortegra, M. Cabre, M. Serra-Prat and V. Arreola\u003c/li\u003e\n \u003cli\u003eUse of thickened liquids in skilled nursing facilities. Journal of the American Dietetic Association. 2004. 104 (8) 1222-6 V.Castellanos, E. Butler, L. Gluch and B. Burke\u003c/li\u003e\n \u003cli\u003eUse of modified diets to prevent aspiration in oropharyngeal dysphagia: is current practice justified? BMC Geriatrics. O\u0026rsquo;Keeffee. 2018. 18: 167\u003c/li\u003e\n \u003cli\u003eThe influence of food texture and liquid consistency modification on swallowing physiology and function: a systematic review. Dysphagia. 2015. 2-26. C. Steele, W. Alsanei, S. Ayanikalath, C. Barbon, J. Chen, J. Chichero, K. Coutts, R. Dantas, J. Duivestein, L. Giosa, B. Hanson, P. Lam, C. Lecko, C. Leigh, A. Nagy, A. Namasivayam, W. Nascimento, I. Odendaal, C. Smith and H. Wang\u003c/li\u003e\n \u003cli\u003eDevelopment of international terminology and definitions for texture modified foods and thickened fluids used in dysphagia management: the IDDSI frame work. Dysphagia. 2016. 293-314. J. Cichero, P. Lam, C. Steele, B. Hanson, J. Chen, R. Dantas, J. Duivestein, J. Kayashita, C. Lecko, J. Murray, M. Pillay, L. Riquelme and S. Sanschus\u003c/li\u003e\n \u003cli\u003ePreferred reporting items for systematic review and meta-analysis protocols (PRIMA-P) 2015: elaboration and explanation. British Medical Journal. 2015 1-25 L.Shamseer, D. Moher, M. Clarke, D. Ghersi, A. Liberati, M. Petticrew, P. Shekelle, and L. Stewart \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCrushed Tablets: Does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release? Journal of pharmacology and pharmaceutical sciences. 2014. 17(2) 207-219 Y. Manrique, D. Lee, F. Islam, L. Nissen, J. Cichero, J. Stokes and K. Steadman\u003c/li\u003e\n \u003cli\u003eEffect of xanthan gum-based food thickeners on the dissolution profile of fluoroquinolones oral formulations. Journal of pharmaceutical health-care and sciences 2020 30(6) N. Takahashi, Y. Fujita, N. Takahashi, A. Nakamura and T. Harada\u003c/li\u003e\n \u003cli\u003eAppropriate usage of food thickening agents to prevent non-disintegration of magnesium oxide tablets. Nature scientific reports. 2020 10(16089) T. Matsuo, A. Sato, K. Kudo, Y. Sadzuka and T. Tomita\u003c/li\u003e\n \u003cli\u003eEffect of xanthan gum as a thickener in widely-used food thickeners on the disintegration of rapidly disintegrating tablets. Japanese Journal of comprehensive rehabilitation science. 2018. (9) 22-28 T. Tomita, T. Fukui, S. Takanohahsi, H. Goto, T. Yoshida K. Sumiya, Y. Kohda and K. Kudo\u003c/li\u003e\n \u003cli\u003eEffect of food thickener on the inhibitory effect of mitiglinide tablets on post-prandial elevation of blood glucose levels. Dysphagia. 2017. 32(3) 449-453 T. Tomita, H. Goto, K. Sumiya, T. Yoshida, K. Tanaka, K. Kudo and Y. Kohda\u003c/li\u003e\n \u003cli\u003eComparison of the effects on tablets disintegration of solvents used to dissolve food thickeners. Journal of texture studies. 2021 52(3) 380-388 T. Matsuo, H. Sasaki, T. Tomita and Y. Sadzuka\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eEffect of thickener on disintegration, dissolution and permeability of common drug products for elderly patients. European journal of pharmaceutics and biopharmaceutics. 2020. 153. 168-176. A.Ruiz-Picazo, S. Colon-Useche, M. Gonzalez-Alvarez, I. Gonzalez-Alvarez, M. Bermejo and P. Langguth\u003c/li\u003e\n \u003cli\u003eEffects of thickened drinks on the disintegration of various oral tablets. Heliyon. 2020. 6(12). T. Matsuo, C. Sato, T. Tomita and Y. Sadzuka\u003c/li\u003e\n \u003cli\u003eCombining liquid oral drugs with thickener: compatibility and changes in viscosity. Dysphagia. 2022. 37 889-899 P. Bravo-Jose, C. Saez-Lleo and E. Moreno-Guillamont\u003c/li\u003e\n \u003cli\u003eEffect of guar gum, a fibre preparation, on digoxin and penicillin absorption in man. European journal of clinical pharmacology. 1984. 26(2) 279-281. R. Huupponen, P. Seppala and E. Lisalo\u003c/li\u003e\n \u003cli\u003eEffect of food thickener on disintegration and dissolution of magnesium oxide tablets. Journal of the pharmaceutical society of Japan. 2015. 135(6) 835-840. T. Tomita, H. Goto, Y. Yoshimura, Y. Tsubouchi, R. Nakanishi, C. Kojima, M. Yoneshima, T. Yoshida, K. Tanaka, K. Sumiya and Y. Kohda\u003c/li\u003e\n \u003cli\u003eEffect of food thickeners on the inhibitory effect of voglibose oral-disintegrating tablets on post-prandial elevation of blood sugar levels. Journal of pharmaceutical society of Japan. 2016. 136(8) 1171-1176. T. Tomita, H. Goto, K. Sumiya, T. Yoshida, K. Tanaka and Y. Kohda\u003c/li\u003e\n \u003cli\u003eEffect of food thickener and jelly water on the pharmacokinetics of levofloxacin orally disintegrating tablets. Heliyon. 2019. 26;5(11). T. Tomita, A. Yamaguchi, N. Nishimura, H. Goto, K. Sumiya, R. Arakawa, T. Yoshida, H. Tachiki, Y. Kohda and K. Kudo\u003c/li\u003e\n \u003cli\u003eFactors affecting prednisolone release from hydrogels prepared with water soluble dietary fibres, xanthan and locust bean gums. Chemical and pharmaceutical bulletin. 1992. 40(2) 459-462. K. Watanabe, S. Yakou, K. Takayama, Y. Machida and T. Nagai\u003c/li\u003e\n \u003cli\u003eOral medication delivery in impaired swallowing: thickening liquid medications for safe swallowing alters dissolution characteristics. Drug development and industrial pharmacy. 2016. 42(9) 1537-1544. Y. Manrique, A. Sparkes, J. Chichero, J. Stokes, L. Nissen and K. Steadman\u003c/li\u003e\n \u003cli\u003eDysphagia in older adults. Mayo Clinic Proceedings. 2021. 96(2) 488 \u0026ndash; 497\u003c/li\u003e\n \u003cli\u003eAdministration of aspirin tablets using a novel gel-based swallowing aid: An open label randomised controlled cross over trial. BMJ innovations. 2019 113-119 D. Wright, J. Potter, A. Clark, A. Blyth, V. Maskrey, G. Mencarelli, S. Wicks and D. Craig\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-geriatric-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"EGEM","sideBox":"Learn more about [European Geriatric Medicine](https://www.springer.com/journal/41999)","snPcode":"41999","submissionUrl":"https://www.editorialmanager.com/egem/default2.aspx","title":"European Geriatric Medicine","twitterHandle":"","acdcEnabled":false,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"dysphagia, swallowing, thickener, modified-diets, thickened-liquids, bioavailability","lastPublishedDoi":"10.21203/rs.3.rs-3199117/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3199117/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDysphagia is associated with long-term conditions including strokes, dementia, Parkinson’s disease and frailty. Dysphagia affects 30-40% of the population aged over 65-years-old. Adults with dysphagia are likely to experience long-term conditions requiring multiple medications (often \u0026gt;5) to manage this. The thickening of liquids is a common compensatory strategy in dysphagia management. Studies suggest that immersion in thickened liquids affects medicines’ solubility in vitro. Clinicians and pharmacists are unaware of the pharmacokinetic/therapeutic effects of thickened liquids on oral medicines. We conducted a systematic review of existing literature on thickeners’ effects on drug bioavailability.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe performed a literature search of MEDLINE and EMBASE. Search terms included: dysphagia/thickened diet (EMBASE only)/ bioavailability or absorption of medicines or pharmacokinetics; excluded: NG feeds/animal studies. Studies included: all genders, countries, \u0026gt;18 years, community and hospital settings. PRISMA guidance was followed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e526 results were found and 15 articles identified following reference list review. Following abstract review, 508 were rejected. 33 received a full text review, 18 were rejected, and the remaining 15 included. Most articles evaluated the effect of thickeners on dissolution profiles of medications in-vitro. Few studies assessed bioavailability or used clinical outcome measures. Often these were small studies on limited numbers of medications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDespite dysphagia and polypharmacy being common in older adults, little is known about the effects of altering liquid viscosity on the pharmacokinetics and therapeutic effect of most medications. Small single-centre studies suggest that immersion in thickener may negatively affect drug pharmacokinetics and therapeutic outcomes.\u003c/p\u003e","manuscriptTitle":"Modified Diets and Medication in Dysphagia – The effect of thickener on drug bioavailability: A systematic review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-08-07 15:59:44","doi":"10.21203/rs.3.rs-3199117/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revisions","date":"2023-09-13T06:55:27+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2023-08-09T09:52:02+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-08-01T09:51:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-08-01T01:22:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Geriatric Medicine","date":"2023-07-30T12:00:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-geriatric-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"EGEM","sideBox":"Learn more about [European Geriatric Medicine](https://www.springer.com/journal/41999)","snPcode":"41999","submissionUrl":"https://www.editorialmanager.com/egem/default2.aspx","title":"European Geriatric Medicine","twitterHandle":"","acdcEnabled":false,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0255b5e2-8084-43a4-b5c7-428075702563","owner":[],"postedDate":"August 7th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2023-10-31T06:00:40+00:00","versionOfRecord":[],"versionCreatedAt":"2023-08-07 15:59:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3199117","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3199117","identity":"rs-3199117","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}