Taste assessment for paediatric drug Development: A comparison of bitterness taste aversion in children versus Naïve and expert young adult assessors.

Medicines for children often taste bitter, presenting a significant challenge to treatment compliance. However, most studies on paediatric drug development rely on adult volunteers for sensory research, and the level of expertise required from these assessors is unclear. This study aimed to address this gap by investigating perceived bitterness aversion to taste strips impregnated with different concentrations of quinine hydrochloride in 439 school-aged children. Expert (n = 26) and naïve (n = 65) young adult assessors evaluated quinine solutions as well as taste strips, for methodological bridging purposes. All assessors differentiated the aversiveness of the taste strips in a dose dependent manner. Younger children aged 4-8 years had difficulty discriminating higher bitter concentrations, whereas pre-adolescents 9-11 years and naive adults showed better discrimination at the top of the scale. Naive assessors showed similar bitter perception as children. However, the results were slightly different between strips and solution in adults. These findings highlight the key role that adult panels can play in paediatric formulation development. Taste strips show promise as a safe and pragmatic tool for sensory pharmaceutical evaluations, though further studies are warranted to establish the relationship between age and hedonic taste perception using compounds with diverse physicochemical and sensory qualities.

Responsive Sensory Evaluation to Develop Flexible Taste-Masked Paediatric Primaquine Tablets against Malaria for Low-Resource Settings.

Primaquine is an important antimalarial drug for malaria transmission blocking and radical cure, but it is not currently available in child-friendly formulations in appropriate doses. Adult-strength tablets are often crushed and dissolved in water to obtain the required dose, which exposes the drug's bitter taste. As part of the developing paediatric primaquine (DPP) project, this study adopted a responsive sensory pharmaceutics approach by integrating real-time formulation development and pre-clinical taste assessment to develop palatable, flavour-infused primaquine tablets. A design of experiment (DoE) approach was used to screen different taste-masking agents and excipient blends with trained, expert sensory assessors, with quinine hydrochloride as a model bitter tastant. The taste-masking efficacy of selected prototype formulation blends was validated with naïve assessors using the highest 15 mg primaquine dose. The mean bitterness intensity rating, measured on a discrete 11-point scale, was halved from 7.04 for the unflavoured control to 2.74-3.70 for the formulation blends. Sucralose had the biggest impact on bitterness suppression and improving palatability. Two different flavouring systems have been developed, and their acceptability in paediatric patients will be assessed as part of upcoming validation field clinical trials in Africa.

I Spy with My Little Eye: A Paediatric Visual Preferences Survey of 3D Printed Tablets.

3D printing (3DP) in the pharmaceutical field is a disruptive technology that allows the preparation of personalised medicines at the point of dispensing. The paediatric population presents a variety of pharmaceutical formulation challenges such as dose flexibility, patient compliance, taste masking and the fear or difficulty to swallow tablets, all factors that could be overcome using the adaptable nature of 3DP. User acceptability studies of 3D printed formulations have been previously carried out in adults; however, feedback from children themselves is essential in establishing the quality target product profile towards the development of age-appropriate medicines. The aim of this study was to investigate the preference of children for different 3D printed tablets (Printlets™) as an important precursor to patient acceptability studies. Four different 3DP technologies; digital light processing (DLP), selective laser sintering (SLS), semi-solid extrusion (SSE) and fused deposition modeling (FDM) were used to prepare placebo printlets with similar physical attributes including size and shape. A single-site, two-part survey was completed with participants aged 4-11 years to determine their preference and opinions based on visual inspection of the printlets. A total of 368 participants completed an individual open questionnaire to visually select the best and worst printlet, and 310 participants completed further non-compulsory open questions to elaborate on their choices. Overall, the DLP printlets were the most visually appealing to the children (61.7%) followed by the SLS printlets (21.2%), and with both the FDM (5.4%) and SSE (11.7%) printlets receiving the lowest scores. However, after being informed that the SSE printlets were chewable, the majority of participants changed their selection and favoured this printlet, despite their original choice, in line with children's preference towards chewable dosage forms. Participant age and sex displayed no significant differences in printlet selection. Printlet descriptions were grouped into four distinct categories; appearance, perceived taste, texture and familiarity, and were found to be equally important when creating a quality target product profile for paediatric 3D printed formulations. This study is the first to investigate children's perceptions of printlets, and the findings aim to provide guidance for further development of paediatric-appropriate medicines using different 3DP technologies.

Correction to: Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Low Dose.

The original version of the article unfortunately contained an error in article title. The corrected title is 'Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Low Dose'.

Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose.

BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium. difficile infection (rCDI). FMT capsules have emerged, and it is unknown if delivery location and dose impact efficacy. METHODS: We compared two cohorts of patients receiving two capsule formulations: gastric release (FMTgr) and targeted colonic release (FMTcr) at two different sites. Cohort A received FMTgr at (1) high dose: 60 capsules and low dose: 30 capsules. Patients in Cohort B received FMTcr at (1) high dose: 30 capsules (2) low dose: 10 capsules. Clinical cure rates and adverse events were monitored through week 8. Paired t-tests were used to compare diversity pre- and post-FMT. RESULTS: 51 rCDI patients were enrolled. Cohort A contained n = 20 and Cohort B contained n = 31. Overall cure at week 8 for FMTgr was 75% (15/20) compared to 80.6% for FMTcr, (25/31), p = 0.63. Both formulations were safe with no serious adverse events. FMTcr was superior at increasing gut microbial diversity. DISCUSSION: To our knowledge, this is the first study to compare targeted delivery of FMT capsules. While both capsules were safe and efficacious, microbial engraftment patterns were superior in FMTcr.

Methodologies for assessing the acceptability of oral formulations among children and older adults: a systematic review.

Acceptability of medicinal products in children and older populations is pivotal in ensuring adherence and therapeutic outcomes. This review systematically identifies studies reporting on formulation aspects of oral medications that affect their acceptability in these patient groups. Particular emphasis is placed on the evaluation of the methodologies employed in the studies. Sixty-eight studies were included for analysis, with 51 (75%) in children and 17 (25%) in older populations. The studies evaluated a range of oral formulations; however, the methodologies used differ considerably in participants' characteristics, study settings, tools, acceptability definitions and criteria. It is evident that there is a lack of standardisation in study design as well as the assessment methods used in assessing acceptability of medicines in children and older populations.

Patient acceptability, safety and access: A balancing act for selecting age-appropriate oral dosage forms for paediatric and geriatric populations.

The selection and design of age-appropriate formulations intended for use in paediatric and geriatric patients are dependent on multiple factors affecting patient acceptability, safety and access. The development of an economic and effective product relies on a balanced consideration of the risks and benefits of these factors. This review provides a comprehensive and up-to-date analysis of oral dosage forms considering key aspects of formulation design including dosage considerations, ease of use, tolerability and safety, manufacturing complexity, stability, supply and cost. Patient acceptability has been examined utilising an evidence-based approach to evaluate regulatory guidance and literature. Safety considerations including excipients and potential risk of administration errors of the different dosage forms are also discussed, together with possible manufacturing and supply challenges. Age appropriate drug product design should consider and compare i) acceptability ii) safety and iii) access, although it is important to recognise that these factors must be balanced against each other, and in some situations a compromise may need to be reached when selecting an age-appropriate formulation.

Acceptability of orodispersible films for delivery of medicines to infants and preschool children.

Orodispersible films (ODFs) possess potential to facilitate oral drug delivery to children; however, documentation of their acceptability in this age group is lacking. This study is the first to explore the initial perceptions, acceptability and ease of use of ODFs for infants and preschool children, and their caregivers through observed administration of the type of dosage form. Placebo ODFs were administered to children stratified into aged 6 to 12 months, 1 year, 2 years, 3 years, 4 years and 5 years old and into those with an acute illness or long-term stable condition in hospital setting. Acceptability of the dosage form and end-user views were assessed by (a) direct observation of administration, (b) questionnaires to caregivers and nurses, and (c) age-adapted questionnaires for children aged 3 years and over. The majority of children (78%) aged 3 years and over gave the ODF a positive rating both on verbal and non-verbal scales. Despite little prior experience, 78% of caregivers expressed positive opinion about ODFs before administration. After the ODFs were taken, 79% of infant caregivers and 86% caregivers of preschool children positively rated their child's acceptance of the ODF. The intraclass correlation coefficient value was 0.92 showing good agreement between ratings of caregivers and nurses. ODFs showed a high degree of acceptability among young children and their caregivers. If drug loading permits, pharmaceutical companies should consider developing pediatric medicines in this format. The methodology described here is useful in assessing the acceptability of active ODF preparations and other dosage forms to children.

Can a Flavored Spray (Pill Glide) Help Children Swallow Their Medicines? A Pilot Study.

Pediatric pharmacists are constantly faced with the challenges of supporting children and caregivers for whom the difficulties of swallowing medicines can be a daily struggle. Most medicines are only available as tablets and capsules, and where liquid alternatives exist, these products often have issues with palatability and high costs. The objective of this study was to evaluate whether the swallowing spray, Pill Glide, could help children in taking their solid and liquid medicines. This open label pilot study compared the spray with a behavioral approach alone, the current standard of care at the pediatric hospital. Patients were children on long-term drug therapies, either transitioning from liquid preparations to tablets and capsules, or known to be experiencing swallowing difficulties. Using age-adapted diaries, patients self-reported the difficulty of taking medicines on a 6-point hedonic scale for 2 weeks before the intervention, and then for 1 week while using Pill Glide. Data were analyzed from 10 children aged 6 to 16 years, with an average burden of 3.5 tablets per day. Pill Glide (strawberry was the most popular flavor) was shown to significantly decrease the overall medicine taking difficulty score by 0.93 (range, 0.33-1.53), almost 1 hedonic face point on the scale used (P = .002). There was insufficient data for liquid medicines. Pill Glide could help children with pill swallowing, thus improving patient acceptability of medicines and potentially adherence. It could also be implemented as a useful cost-saving intervention because solid dosage forms are cheaper.

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children's Acceptability of Oral Formulations (CALF) Study.

A lack of evidence to guide the design of age-appropriate and acceptable dosage forms has been a longstanding knowledge gap in paediatric formulation development. The Children's Acceptability of Oral Formulations (CALF) study captured end-user perceptions and practices with a focus on solid oral dosage forms, namely tablets, capsules, chewables, orodispersibles, multiparticulates (administered with food) and mini-tablets (administered directly into the mouth). A rigorous development and testing phase produced age-adapted questionnaires as measurement tools with strong evidence of validity and reliability. Overall, 590 school children and adolescents, and 428 adult caregivers were surveyed across hospitals and various community settings. Attitudes towards dosage forms primarily differed based on age and prior use. Positive attitudes to tablets and capsules increased with age until around 14 years. Preference was seen for chewable and orodispersible preparations across ages, while multiparticulates were seemingly less favourable. Overall, 59.6% of school children reported willingness to take 10mm diameter tablets, although only 32.1% of caregivers perceived this size to be suitable. While not to be taken as prescriptive guidance, the results of this study provide some evidence towards rational dosage form design, as well as methodological approaches to help design tools for further evaluation of acceptability within paediatric studies.