Innovative, Sugar-Free Oral Hydrogel as a Co-administrative Vehicle for Pediatrics: a Strategy to Enhance Patient Compliance.

Palatability and swallowability in the pediatric population are perceived as true challenges in the oral administration of medication. Pediatric patients have high sensitivity to taste and reduced ability to take solid dosage forms, which can often lead to a poor therapeutic compliance. It is crucial to find new strategies to simplify the oral administration of drugs to children. The present paper reports the development of a new hydrogel vehicle adapted to the pediatric population. Several polymers with similar properties were selected and adjustments were made to obtain the desired characteristics of the final product. The developed formulations were studied for organoleptic properties, rheology, mucoadhesion properties, preservative efficacy, and stability. Physical and chemical compatibilities between the vehicle and several drugs/medicines, at the time of administration, were also studied. Six final formulations with different polymers, odor, and color were chosen, and no known interactions with medications were observed. The proposed new oral vehicles are the first sugar-free vehicle hydrogels designed to make the intake of oral solid forms a more pleasant and safer experience for pediatric patients.

Acceptability of oral liquid pharmaceutical products in older adults: palatability and swallowability issues.

BACKGROUND: In institutional care, oral liquid pharmaceutical products are widely prescribed for older patients, especially for those with swallowing disorders. As medicines acceptability is a key factor for compliance in the older population, this study investigated the acceptability of oral liquid pharmaceutical products in this targeted population. METHODS: An observational, multicenter, prospective study was conducted in eight geriatric hospitals and eight nursing homes in France. Observers reported several behaviours/events describing the many aspects of acceptability for various pharmaceutical products' uses in patients aged 65 and older. Acceptability scores of oral liquid pharmaceutical products were obtained using an acceptability reference framework (CAST - ClinSearch Acceptability Score Test®): a 3D-map summarizing the different users' behaviors, with two clusters defining the positively and negatively accepted profiles materialized by the green and red zones, respectively. RESULTS: Among 1288 patients included in the core study and supporting the acceptability reference framework, 340 assessments were related to the administration of an oral liquid pharmaceutical product. The mean age of these patients was 87 (Range [66-104y]; SD = 6.7), 68% were women and 16% had swallowing disorders. Globally, the oral liquid pharmaceutical products were classified as "positively accepted," the barycenter of the 340 assessments, along with the entire confidence ellipses surrounding it, were positioned on the green zone of the map. Sub-populations presenting a different acceptability profile have also been identified. For patients with swallowing disorders, the oral liquid pharmaceutical products were classified as "negatively accepted," the barycenter of the 53 assessments along with 87% of its confidence ellipses were associated with this profile. A gender difference was observed for unflavored oral liquids. In women, they were classified "negatively accepted," the barycenter of the 68 assessments with 75% of its confidence ellipses were located in the red zone, while they were classified "positively accepted" in men. CONCLUSION: This study showed that oral liquid pharmaceutical products are a suboptimal alternative to solid oral dosage forms in patients with swallowing disorders. To ensure an optimal acceptability, prescribers should also consider the presence of a taste-masker in these oral liquids. As highlighted herein, palatability remains crucial in older populations, especially for women.

Acceptability of Multiple Uncoated Minitablets in Infants and Toddlers: A Randomized Controlled Trial.

OBJECTIVES: To assess the acceptability and swallowability of several minitablets when administered as a unit dose compared with an equivalent dose of syrup in children aged 6 months to 5 years. STUDY DESIGN: The acceptability and swallowability of multiple drug-free minitablets in comparison with glucose syrup was assessed in 372 children of 2 age groups (186 in age group 1 [6-23 months of age] and 186 in age group 2 [2-5 years of age]) in a randomized, 3-way, single administration cross-over study. Age group 1 received 25 minitablets, 100 minitablets, and 5 mL syrup. Age group 2 received 100 minitablets, 400 minitablets, and 10 mL syrup. RESULTS: Superiority was demonstrated in age group 1 for acceptability (25 minitablets, P < .017; 100 minitablets, P < .0001) and swallowability (25 minitablets and 100 minitablets, both P < .0001) compared with syrup. In age group 2, noninferiority of acceptability was found only for 400 minitablets (P < .0003), not for 100 minitablets. Subgroup analysis revealed a strong sequential effect. For swallowability, noninferiority could be demonstrated for 100 minitablets (P < .01) but not for 400 minitablets. CONCLUSIONS: Administration of ≥25 minitablets is well-tolerated, feasible, and safe in children aged from 6 months, and was superior to the equivalent dose of syrup. Children aged >1 year accept ≤400 minitablets even better than the equivalent dose of syrup. Minitablets open the perspective for introducing small-sized solid drug formulations for all children, thus, further shifting the paradigm from liquid toward small-sized solid drug formulations. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00008843.

A Decision Support Tool Facilitating Medicine Design for Optimal Acceptability in The Older Population.

PURPOSE: Medicine acceptability, which is of the utmost importance for vulnerable patients' adherence, is driven by both user and product characteristics. Herein, a novel multivariate approach integrating the many aspects of acceptability is used to discriminate positively and negatively accepted medicines in the older population. METHODS: An observational study was carried out in eight hospitals and eight nursing homes to collect a large set of real-life data on medicines uses in older patients (≥65 years). Mapping and clustering explored these multiple observational measures and summarised the main information into an intelligible reference framework. Resampling statistics were used to validate the model's reliability. RESULTS: A three-dimensional map and two clusters defining acceptability profiles, as positive or negative, emerged from the 1079 evaluations. Factors of interest (medicines, user features…) were positioned on the map at the barycentre of their evaluations and assigned to an acceptability profile. Focusing on patients' ability to swallow, we have highlighted the tool's efficacy in demonstrating the impact of user features on medicine acceptability. CONCLUSIONS: This multivariate approach provides a relevant judgement criterion for this multi-dimensional concept. Facilitating the choice of the most appropriate dosage form to achieve optimal acceptability in a targeted population, this tool is of real potential to improve clinical decisions.

Acceptability of Mini-Tablets in Young Children: Results from Three Prospective Cross-over Studies.

To ensure optimal, reliable treatment, it is necessary to investigate the efficacy, safety and the optimal dose of drug substances and to develop suitable age-specific pharmaceutical formulations for the different paediatric age groups due to a lack of evidence-based therapeutic options for children. While WHO recommends the use of solid dosage forms in general, European Medicines Agency (EMA) requires evidence for the suitability of these dosage forms in the targeted age group. This review aims to summarize and discuss the data obtained in acceptability studies on the suitability of coated and uncoated mini-tablets in children of different ages in comparison to a sweet syrup considered as gold standard. The predefined outcome parameters 'acceptability' and 'capability to swallow' of the two different mini-tablet formulations (uncoated and film-coated) were statistically significantly higher than that of the syrup.

Validating a composite endpoint for acceptability evaluation of oral drug formulations in the pediatric population: a randomized, open-label, single dose, cross-over study.

Objective: This study aimed to validate the newly developed composite acceptability endpoint to investigate acceptability of oral pediatric drug formulations that integrates swallowability and palatability assessments. Methods: In this open-label study acceptability of oral formulations was tested in three age groups (1-<6 months, 6-<12 years, and 12-<18 years) with a 2-way cross-over design in children aged 1-<6 months (syrup and mini-tablets), and with an incomplete block design of four sequences with three out of four formulations (syrup, mini-tablets, oblong tablet, and round tablet) each in children aged 6-<18 years. The primary endpoint was acceptability derived from the composite acceptability endpoint. Secondary endpoints were palatability and acceptability derived from swallowability. Results: A total of 320 children were stratified into three age groups (80 children aged 1-<6 months, 120 children aged 6-<12 years, and 120 children aged 12-<18 years). All participants completed the study. Age-specific differences were observed in acceptability derived from the composite acceptability endpoint. Mini-tablets had the highest acceptability in participants aged 1-<6 months and 6-<12 years while the oblong tablet was leading in adolescent participants (12-<18 years). Conclusion: This study demonstrated that the composite acceptability endpoint method integrating both swallowability and palatability assessments is a sensitive method to assess acceptability of drug formulations in children of different age. Clinical Trial Registration: https://drks.de/search/de, identifier DRKS00027948.

Designs of clinical swallowability assessments of solid oral dosage forms in regulatory submissions.

The swallowability of solid oral dosage forms (SODFs) is crucial for medication safety and adherence. Both regulatory agencies and sponsors are concerned with bringing swallowable SODFs to patients. However, no best practices are available for assessing swallowability. Therefore, we conducted a comparative analysis of clinical swallowability assessments (CSAs) for SODFs in regulatory submissions to identify current study design practices. CSAs were identified from a "swallowability" keyword search of a Food and Drug Administration database. Notable design trends among the 17 CSAs were not assessing swallowability as a primary endpoint (76 %); enrolling pediatric patients (76 %); administering assessments post-screening (76 %); and utilizing questionnaires (100 %). A design trend with near equal frequency (∼50 %) was single- or multiple-doses of product administration. Study subjects were the primary questionnaire respondents (82 %), usually using a Likert scale (92 %, 12/13). CSAs generally dichotomized the responses for analysis (65 %) without pre-specified threshold values (59 %). Overall, while study designs exhibited trends, methodology variations may impact swallowability measurements affecting the interpretation of results. Thus, developing robust and valid assessment tools for swallowability is imperative to produce clinically relevant data and inform regulatory decision-making. Collaboration between regulatory agencies and sponsors is warranted to create best practices and ensure high quality swallowability data.

Preference for a Novel Oral Alternative to Parenterally Administered Medications.

Background: Rani Therapeutics is developing a robotic pill (RP), an oral drug delivery platform called RaniPill™ that can deliver a number of biotherapeutics with high bioavailability; eliminating the need for injections. While patients in general prefer oral to injectable therapies, preference for a more frequent oral regimen compared to a less frequent injectable regimen is unknown. Two marketing surveys were conducted to gather data on preference for oral versus injectable therapies. A clinical study gathered data on participant preference for oral pills vs injections before and after swallowing a Mock-RP capsule. Methods: A total of 1689 adults taking injections (mean duration 3-7 years) to treat endocrine or inflammatory conditions were anonymously surveyed online for their preference to administer/prescribe medications orally via the RP. In the clinical study, 150 participants currently taking injections for chronic conditions evaluated the swallowability of a Mock-RP and completed a questionnaire regarding their preferences. Results: Majority of respondents surveyed stated they would be willing to convert to an oral alternative over their current parenteral therapy regardless of drug or disease. In the clinical study, all participants were able to swallow the Mock-RP and 91% indicated their preference for the oral route versus their current parenteral route of drug administration. Survey respondents and those in the clinical study using frequent injections were more willing to select a once-daily capsule compared to those injecting infrequently. Even study participants who inject infrequently (≥monthly: 80%) would prefer a once-daily pill over their injection regimen. Conclusion: Patients taking injections and prescribing physicians strongly prefer oral dosing to parenteral administration of biologics even if dosing frequency with the oral option, such as the RP, is increased.

Assessment of swallowability and acceptability of scored darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) tablets in HIV-1-infected children aged ≥6 to <12 years, using matching placebo tablets: A randomized study.

BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) was developed as a once-daily, complete antiretroviral (ARV) regimen therapy to address the need for simplified protease inhibitor-based ARV regimens. This study assessed the swallowability and acceptability for long-term use of scored placebo tablets matching the D/C/F/TAF FDC tablets in children living with HIV-1. METHODS: This study (NCT04006704) was a Phase 1, open-label, randomized, single-dose, 2-period, 2-sequence crossover study in children living with HIV-1, aged ≥6 to <12 years and weighing ≥25 to <40 kg, on a stable ARV regimen for ≥3 months. Participants were asked to swallow whole (size, 21 × 11 × 7 mm) and split matching placebo D/C/F/TAF tablets. Swallowability of the matching placebo D/C/F/TAF tablets (primary endpoint) was assessed by observers. Acceptability of taking matching placebo D/C/F/TAF tablets and current ARVs was evaluated by participants using a 3-point questionnaire. Participants rated the acceptability for long-term daily use of the placebo D/C/F/TAF tablets, and observers assessed how easily caregivers could split a scored tablet by hand, using 3-point questionnaires. RESULTS: Among the 24 participants who enrolled and completed the study, 95.8% (23/24) were able to swallow the whole and split matching placebo D/C/F/TAF tablets after 1 or 2 attempts. Most participants (>70%) rated the acceptability of tablets for long-term daily use as acceptable or good to take. Breaking the tablets was considered easy or OK by 79.2% (19/24) of caregivers. CONCLUSION: Scored D/C/F/TAF FDC tablets are swallowable - with whole favoured over split - and considered at least acceptable for long-term daily intake in children living with HIV-1 aged ≥6 to <12 years. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04006704.

Minitablets current use and future opportunities - An APV course on manufacturing, packaging, characterization and use of minitablets.

Recently, APV organized in collaboration with Fette Compacting GmbH a course on current use and future opportunities of minitablets. The course including a workshop was attended by 30 participants and focused on the manufacturing, packaging, characterization and medical use of minitablets. It took place at the Headquarter of Fette Compacting GmbH in Schwarzenbek. This article provides an overview on the topics presented and discussed during the course.

Evaluating the Acceptability, Swallowability, and Palatability of Film-Coated Mini-Tablet Formulation in Young Children: Results from an Open-Label, Single-Dose, Cross-Over Study.

Mini-tablets are advantageous over liquid formulations in overcoming challenges related to stability, taste, and dosage. This open-label, single-dose, cross-over study investigated the acceptability and safety of drug-free, film-coated mini-tablets in children aged 1 month-6 years (stratified: 4-6 years, 2-<4 years, 1-<2 years, 6-<12 months, and 1-<6 months), and their preference for swallowing either a high quantity of 2.0 mm or a low quantity of 2.5 mm diameter mini-tablets. The primary endpoint was acceptability derived from swallowability. The secondary endpoints were investigator-observed palatability, acceptability as a composite endpoint derived from both swallowability and palatability, and safety. Of 320 children randomized, 319 completed the study. Across all tablet sizes, quantities and age groups, acceptability rates based on swallowability were high (at least 87%). Palatability was rated as "pleasant/neutral" in 96.6% of children. The acceptability rates as per the composite endpoint were at least 77% and 86% for the 2.0 mm and 2.5 mm film-coated mini-tablets, respectively. No adverse events or deaths were reported. Recruitment in the 1-<6-months group was stopped early due to coughing-evaluated as "choked on" in three children. Both 2.0 mm and 2.5 mm film-coated mini-tablets are suitable formulations for young children.

Impact of Tablet Size and Shape on the Swallowability in Older Adults.

Older adults represent the major target population for oral medications, due to the high prevalence of multimorbidity. To allow for successful pharmacological treatments, patients need to adhere to their medication and, thus, patient-centric drug products with a high level of acceptability by the end users are needed. However, knowledge on the appropriate size and shape of solid oral dosage forms, as the most commonly used dosage forms in older adults, is still scarce. A randomized intervention study was performed including 52 older adults (65 to 94 years) and 52 young adults (19 to 36 years). Each participant swallowed four coated placebo tablets differing in weight (250 to 1000 mg) and shape (oval, round, oblong) in a blinded manner on three study days. The choice of tablet dimensions allowed for a systematic comparison between different tablet sizes of the same shape, as well as between different tablet shapes. Swallowability was assessed using a questionnaire-based method. All tested tablets were swallowed by ≥80% of adults, independent of age. However, only the 250 mg oval tablet was classified as well swallowable by ≥80% of old participants. The same was true for young participants; however, they also considered the 250 mg round and the 500 mg oval tablet as well swallowable. Furthermore, swallowability was seen to influence the willingness to take a tablet on a daily basis, especially for an intake over longer time periods.

Acceptability, Swallowability, Palatability, and Safety of Multiple Film-Coated Mini-Tablets in Children Aged ≥2-<7 Years: Results of an Open-Label Randomised Study.

This single-centre, open-label, randomised, parallel-group study assessed the acceptability, swallowability, palatability, and safety of film-coated, 3 mm diameter mini-tablets in children aged ≥2-<7 years. In total, 300 participants were randomised (2:2:1:1) to receive a single oral administration of 16 (group A) or 32 (group B) mini-tablets with soft food or 16 (group C) or 32 (group D) mini-tablets with water. Children in each group were stratified by age group (2-<3 years; 3-<4 years; 4-<5 years; 5-<6 years; and 6-<7 years). Groups C and D were pooled for statistical analyses. The rates of acceptability (swallowed ≥80% of the mini-tablets with or without chewing), swallowability (swallowed all mini-tablets without chewing or any leftover), and palatability (positive/neutral responses) were ≥80.0%, ≥42.0%, and ≥82.0%, respectively, across the study groups. No marked differences were observed between groups or across age groups. No adverse events or issues of clinical relevance with deglutition were reported. Mini-tablets taken with soft food or water provide a suitable method for administering medicines to children aged ≥2-<7 years. This study was registered in the German Clinical Trial Register (No. DRKS00024617).

Dosage Forms Suitability in Pediatrics: Acceptability of Antibiotics in a German Hospital.

Although drug acceptability can have a significant impact on patient adherence in pediatric therapy, data are limited, even for common therapeutic areas. We present the second part of an acceptability study conducted at the University Children's Hospital Düsseldorf, Germany. The study investigated the acceptability of most commonly used antibiotics in a pediatric hospital setting. The researchers used the acceptability reference framework to score the acceptability of five antibiotics based on 150 real-life observer reports of medicine intake. Four antibiotics assessed in this study were formulated as preparations for injection (ampicillin, ampicillin/sulbactam, ceftriaxone, and gentamicin) and one as a powder for oral liquid suspension (co-amoxiclav). All the antibiotics formulated as preparations for injection were rated negatively due to high rates of negative reactions (80%), the use of restraint (51%), the use of extra devices (99%), and long preparation and administration times (100%). The antibiotic formulated as a powder was significantly more well accepted. The study concluded that there is a lack of appropriate formulations for antibiotics for use in children. These findings are important in improving knowledge on acceptability drivers and might help in formulating and prescribing better medicines for children. The study highlights the need for healthcare professionals to have knowledge about the acceptability of different products to select the best-adapted product for each patient.

Young patients' involvement in a composite endpoint method development on acceptability for paediatric oral dosage forms.

BACKGROUND: In line with the European Paediatric Regulation, the European Medicines Agency (EMA) asks for investigation of a medicine's acceptability in paediatric medicines development. A standardised acceptability testing method combining the outcome of "swallowability" and "palatability" assessments to a "composite endpoint on acceptability" was recently developed. Before this method's suitability for selection of the most acceptable drug formulation of a new medicine for children can be broadly recommended, the acceptance and relevance of such established acceptability needs the critical review and input from young patients with understanding of the medicines development methodology. The benefit of involving patients in drug product development, clinical research and innovation is well established. METHODS: During a focus group meeting with the KIDS Barcelona (young people advisory group, age 16-23 years) the suitability of the "composite endpoint on acceptability" methodology was assessed. Via electronic questionnaires the importance of involving patients in the medicines development and in the acceptability method development was investigated. Questions on how best to determine palatability and swallowability were asked. The relevance of all EMA-listed acceptability elements was assessed via coloured and numbered stickers and questionnaires. RESULTS: The results showed that the involvement of young people in the medicines and acceptability method development was rated high. The group worked out that a 5-point smiley Likert Scale is preferred for assessing acceptability by 6-11 year old patients, while a Visual Analogue Scale is preferred for collecting adolescents' opinion. The ranking of the EMA-listed acceptability elements showed that palatability and swallowability are the most relevant parameters, while colour of the medicine was rated as least relevant. These results, established face-to-face, were confirmed in a repeat of the ranking through an electronic questionnaire, completed by the participants individually and remotely, 5 weeks later. CONCLUSION: This work reinforced the need and value to involve young people in the medicines lifecycle, and specifically in this acceptability method development. As next step other focus group meetings with more young people from different European countries are planned.

Before a new medicine is authorized, its acceptability by children must be investigated according to law. An acceptability testing method combining the outcomes of "swallowability" and "palatability" assessments was recently developed. During a focus group meeting with KIDS Barcelona (young people advisory group, age 16­23 years) their opinion on the suitability of the method and the relevance of patient engagement in the medicines development process were assessed with paper-based and electronic questionnaires. Questions on how best to determine palatability and swallowability were asked. The importance of different elements that typically affect acceptability was rated. The order of relevance of those listed acceptability elements was assessed using coloured and numbered stickers and questionnaires. The results showed that the involvement of young people in the medicines and acceptability method development was rated high. The group worked out that a 5-point smiley Likert Scale that allows for marking a choice between total agreement and total disagreement is preferred for assessing acceptability by 6­11 year old patients. A Visual Analogue Scale (scale consisting of a 10 cm long line on which a mark has to be placed at the desired position, between total agreement and total rejection) is preferred for collecting adolescents' (12­18 years) opinion. The ranking of acceptability elements showed that palatability and swallowability of a new medicine are the most relevant parameters, and colour the least. The clarity of the outcome reinforced the benefit of involving young people in the development of medicines relevant for children.

Influence of Solid Oral Dosage Form Characteristics on Swallowability, Visual Perception, and Handling in Older Adults.

Swallowability, visual perception, and any handling to be conducted prior to use are all influence factors on the acceptability of an oral dosage form by the patient. Knowing the dosage form preferences of older adults, as the major group of medication end users, is needed for patient-centric drug development. This study aimed at evaluating the ability of older adults to handle tablets as well as to assess the anticipated swallowability of tablets, capsules, and mini tablets based on visual perception. The randomized intervention study included 52 older adults (65 to 94 years) and 52 younger adults (19 to 36 years). Within the tested tablets, ranging from 125 mg up to 1000 mg in weight and being of different shapes, handling was not seen as the limiting factor for the decision on appropriate tablet size. However, the smallest sized tablets were rated worst. According to visual perception, the limit of acceptable tablet size was reached at around 250 mg for older adults. For younger adults, this limit was shifted to higher weights and was dependent on the tablet shape. Differences in anticipated swallowability with respect to tablet shapes were most pronounced for tablets of 500 mg and 750 mg in weight, independent of the age category. Capsules performed worse compared to tablets, while mini tablets appeared as a possible alternative dosage form to tablets of higher weight. Within the deglutition part of this study, swallowability capabilities of the same populations were assessed and have been reported previously. Comparing the present results with the swallowing capabilities of the same populations with respect to tablets, it shows adults' clear self-underestimation of their ability to swallow tablets independent of their age.

A Composite Endpoint for Acceptability Evaluation of Oral Drug Formulations in the Pediatric Population.

INTRODUCTION: A medicine's acceptability is likely to have significant impact on pediatric adherence. The importance is underlined in EMA and FDA guidance on this topic where investigation of acceptability is stated as a regulatory expectation. Demonstrating acceptability can be challenging given there is no globally recognized definition and no standardized testing methodology or assessment criteria. Palatability and swallowability are generally recognized as important elements of acceptability, and this work proposes a definition of acceptability using these elements to give a composite endpoint for acceptability for pediatric subjects across all age ranges. METHODS: This composite acceptability endpoint is based on validated assessment methods for swallowability and palatability in children of different age groups using different galenic placebo formulations, in line with criteria proposed by EMA for assessing acceptability in children from newborn to 18 years of age. Data from two studies investigating mini-tablets, oblong tablets, orodispersible films, and syrup were analyzed to establish the validity, expediency, and applicability of the suggested composite acceptability assessment tool. RESULTS: The new composite endpoint is an efficient and suitable way to distinguish preferences of oral formulations: Mini-tablets and oblong tablets had significantly better acceptability than syrups and orodispersible films. CONCLUSION: Since the suggested acceptability criteria takes both swallowability and palatability into account as composite endpoint, it is highly sensitive to detect acceptability differences between oral formulations. It is a well-defined valid approach, which meets regulatory requirements in an appropriate and comprehensive manner and may in future serve as a pragmatic, standardized method to assess and compare acceptability of pediatric formulations with active substances.

Preference, Perception, and Acceptability of Fluid Gels as a Potential Age-Appropriate Dosage Form for Elderly Patients with Dysphagia.

The development of pharmaceutical dosage forms that are tailored to specific populations according to their preferences and acceptability could improve medication adherence, which could lead to effective pharmacotherapy. This study evaluated the preference for and perceptions of fluid gels as a potential age-appropriate dosage form for older adults with dysphagia. The palatability and swallowability of the developed fluid gels were also assessed to determine the consumer acceptability of this formulation. A cross-sectional survey was conducted through the electronic distribution of a self-administered questionnaire among adults in Malaysia between April and December 2021. A randomized and double-blinded clinical study was conducted to evaluate the palatability and swallowability of the fluid gels in 30 healthy participants. A cross-sectional study involving 673 respondents revealed that the fluid gels were perceived positively by consumers (64.4%), were easily swallowed (50.8%), were safe to be consumed (45.3%), and were suitable as a new pharmaceutical formulation (43.8%). The clinical study shows that moderately thickened fluid gels masked the bitterness of the medication and were easily swallowed. The newly developed fluid gels were also positively perceived by the participants. Taken together, fluid gels have shown great potential as an innovative oral formulation that is suitable for consumption by elderly patients with dysphagia.

Dosage Forms Suitability in Pediatrics: Acceptability of Analgesics and Antipyretics in a German Hospital.

Although medicine acceptability is likely to have a significant impact on the patient's adherence in pediatrics and therefore on therapy success, there is still little data even for common therapeutic areas. For analgesics/antipyretics, healthcare professionals face a wide variety of products and need knowledge to select the best adapted product for each patient. We investigated acceptability of those products most used at the University Children's Hospital Düsseldorf, Germany. Based on 180 real-life observer reports of medicine intake, we used the acceptability reference framework to score acceptability of six distinct medicines. Both ibuprofen and paracetamol tablets, mainly used in adolescents, were positively accepted. This was not the case for the solution for injection of metamizole sodium. Regarding syrups, mainly used in children under 6 years of age, ibuprofen flavored with strawberry and provided with an oral syringe was positively accepted, while paracetamol flavored with orange and provided with a measuring cup was not. Suppository appeared to be an alternative to oral liquids in infants and toddlers with palatability and administration issues. Differences appeared to be driven by dosage forms and formulations. These findings improve knowledge on acceptability drivers and might help formulating and prescribing better medicines for children.

Multi-Analytical Framework to Assess the In Vitro Swallowability of Solid Oral Dosage Forms Targeting Patient Acceptability and Adherence.

A lack of effective intervention in addressing patient non-adherence and the acceptability of solid oral dosage forms combined with the clinical consequences of swallowing problems in an ageing world population highlight the need for developing methods to study the swallowability of tablets. Due to the absence of suitable techniques, this study developed various in vitro analytical tools to assess physical properties governing the swallowing process of tablets by mimicking static and dynamic stages of time-independent oral transitioning events. Non-anatomical models with oral mucosa-mimicking surfaces were developed to assess the swallowability of tablets; an SLA 3D printed in vitro oral apparatus derived the coefficient of sliding friction and a friction sledge for a modified tensometer measured the shear adhesion profile. Film coat hydration and in vitro wettability was evaluated using a high-speed recording camera that provided quantitative measurements of micro-thickness changes, simulating static in vivo tablet-mucosa oral processing stages with artificial saliva. In order to ascertain the discriminatory power and validate the multianalytical framework, a range of commonly available tablet coating solutions and new compositions developed in our lab were comparatively evaluated according to a quantitative swallowability index that describes the mathematical relationship between the critical physical forces governing swallowability. This study showed that the absence of a film coat significantly impeded the ease of tablet gliding properties and formed chalky residues caused by immediate tablet surface erosion. Novel gelatin- and λ-carrageenan-based film coats exhibited an enhanced lubricity, lesser resistance to tangential motion, and reduced stickiness than polyvinyl alcohol (PVA)-PEG graft copolymer, hydroxypropyl methylcellulose (HPMC), and PVA-coated tablets; however, Opadry® EZ possessed the lowest friction-adhesion profile at 1.53 a.u., with the lowest work of adhesion profile at 1.28 J/mm2. For the first time, the in vitro analytical framework in this study provides a fast, cost-effective, and repeatable swallowability ranking method to screen the in vitro swallowability of solid oral medicines in an effort to aid formulators and the pharmaceutical industry to develop easy-to-swallow formulations.