A novel oral syringe for dosing and administration of multiparticulate formulations : acceptability study in preschool and school children

The popularity of multiparticulate formulations (MPs) as a paediatric dosage form continues to increase. MPs comprise of multiple small units that are easy-to-swallow. Currently, MPs are commonly manufactured into unit doses that are either swallowed whole or opened prior to administration. While this is an acceptable approach, dosing is envisioned to be optimised with a “standard” paediatric device which can better harness the flexible dosing potential of MPs. We evaluated a novel oral syringe (Sympfiny™, HS Design, Morristown, NJ, USA) that is being developed as a tool to dispense and administer MPs to children. Forty children, 4–12 years old, received 0.5, 1.2, and 2.0 mL doses of placebo MPs using the oral syringe with spring water or a drink of choice to complete sample intake. Acceptability was recorded as those able to completely swallow the dose and participants also rated dose acceptability on a 5-point scale. The ability to completely swallow the dose decreased as dose volume increased; the smallest dose was completely swallowed by 87.5% (35/40) children, and 69.4% (27/39) of children confirmed their willingness to take the sample as a daily medicine. Larger doses, 1.2 and 2.0 mL, gave values of 55% and 57.5% for the doses completely swallowed and 58.8% and 51.72% for willingness to take the sample as a daily medicine, respectively. Use of a drink of choice showed no increase in swallowability as compared with water. The novel oral syringe being developed is an appropriate device for dispensing doses flexibly and administering neutral tasting MPs directly to the mouth in the lower dose range without the need for a co-administration vehicle in children aged 4–12 years

Acceptability of placebo multiparticulate formulations in children and adults

Patient acceptability is an important consideration in the design of medicines for children. The aim of this study was to investigate acceptability of multiparticulates in healthy children and adults. A randomised, single-blind acceptability testing was performed involving 71 children (4-12 years) and 61 adults (18-37 years). Each participant received three 500 mg samples of microcrystalline cellulose pellets administered on a medicine spoon with water at 5-10 minutes intervals. Acceptability was measured based on voluntary intake of the samples, facial expressions, ratings on hedonic scales and reported willingness to take multiparticulates everyday as a medicine. Multiparticulates were voluntarily swallowed by 92% of children and 100% of adults. However, palatability issues were identified, with emphasis on textural aspects. Grittiness perception received negative ratings on hedonic scales by 60% of children and 51% of adults. Researcher observations revealed that 72% of children and 42% of adults displayed negative facial expressions towards the samples. Children reported their willingness to take multiparticulates as a medicine in 30% of the cases, compared to 74% in adults. This study demonstrates that multiparticulates may be a suitable formulation platform for children and adults, although palatability concerns have been highlighted. Additional work is required to define acceptability criteria and to standardise methodologies

Scoping potential routes to UK civil unrest via the food system: Results of a structured expert elicitation

We report the results of a structured expert elicitation to identify the most likely typesof potential food system disruption scenarios for the UK, focusing on routes to civil unrest. Wetake a backcasting approach by defining as an end-point a societal event in which 1 in 2000 peoplehave been injured in the UK, which 40% of experts rated as “Possible (20–50%)”, “More likely thannot (50–80%)” or “Very likely (>80%)” over the coming decade. Over a timeframe of 50 years, thisincreased to 80% of experts. The experts considered two food system scenarios and ranked theirplausibility of contributing to the given societal scenario. For a timescale of 10 years, the majorityidentified a food distribution problem as the most likely. Over a timescale of 50 years, the expertswere more evenly split between the two scenarios, but over half thought the most likely route tocivil unrest would be a lack of total food in the UK. However, the experts stressed that the variouscauses of food system disruption are interconnected and can create cascading risks, highlighting theimportance of a systems approach. We encourage food system stakeholders to use these results intheir risk planning and recommend future work to support prevention, preparedness, response andrecovery planning

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Utilising Co-Axial Electrospinning as a Taste-Masking Technology for Paediatric Drug Delivery

The present study describes the use of two taste-masking polymers to fabricate a formulation of chlorpheniramine maleate for paediatric administration. Co-axial electrospinning was utilized to create layered nanofibres; the two polymers, Eudragit® E PO and Kollicoat® Smartseal, were alternated between the core and the shell of the system in order to identify the optimum taste-masked formulation. The drug was loaded in the core on all occasions. It was found that the formulation with Kollicoat® Smartseal in the core with the drug, and Eudragit® E PO in the shell showed the most effective taste-masking compared to the other formulations. These fibres were in the nano-range and had smooth morphology as verified by scanning electron microscopy. Solid-state characterization and thermal analysis confirmed that amorphous solid dispersions were formed upon electrospinning. The Insent E-tongue was used to assess the taste-masking efficiency of the samples, and it was found that this formulation was undetectable by the bitter sensor, indicating successful taste-masking compared to the raw version of the drug. The E-tongue also confirmed the drug’s bitterness threshold as compared to quinine HCl dihydrate, a parameter that is useful for formulation design and taste-masking planning