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Oral liquid prednisolone medications have poor acceptance among paediatric patients due to ineffective masking of the bitterness taste of prednisolone. This study aimed to develop a child-friendly prednisolone tablet using a patented chewable chocolate-based delivery system (CDS) previously applied successfully to mask the bitterness tastes of midazolam and tramadol. Prednisolone sodium phosphate (PSP) and prednisolone base (PB) CDS tablets were prepared, and the manufacturing process was optimised using a design of experiments (DoE) approach. Stability was assessed by quantifying residual drug content via a validated HPLC assay. A pilot randomised crossover taste study involving 25 young adult volunteers evaluated taste-masking effectiveness against Redipred™, a commercial oral PSP liquid medicine. The results showed that the PSP CDS tablet was chemically stable following storage for three months at ambient temperature, while the PB CDS tablet was unstable. The optimised PSP CDS tablet, manufactured at 50 °C with a stirring time of 26 h, was found to release over 80% of its drug load within 20 min in 0.1 M HCl and had a significantly better mean taste score compared to Redipred™ (7.08 ± 2.40 vs. 5.60 ± 2.33, p = 0.03). Fifty six percent of the participants preferred the PSP CDS tablet. In conclusion, compared to Redipred™, the CDS technology provided a more effective taste masking of PSP, potentially offering a child-friendly prednisolone formulation with improved compliance, dosing accuracy, and storage stability. [ABSTRACT FROM AUTHOR]

[Display omitted] Mini-tablets (MTs) with losartan potassium were developed to treat the rare disease Epidermolysis Bullosa. The focus was placed on transfer and scale-up of a direct compressible formulation from the compaction simulator STYL'One Evo (CS) to the rotary tablet press Korsch XM 12 (RP). Transfer of tabletability and compactibility profiles from CS to RP did not show good agreement, e.g. at a tableting pressure of 125 MPa mean tensile strengths (TS) of 4 MPa on CS and 1–1.5 MPa on RP were reached. These results highlight the impact of the feed frame on final product qualities depending on process and material factors. In the scale-up studies the critical quality attributes (CQAs) mass variation, content uniformity, TS and disintegration time were investigated. After an appropriate run-up time, most CQAs reached a plateau, after reaching a balance between influx, efflux and distribution of lubricant in the feed frame. TS values of 1–2 MPa, disintegration times of max. 50 s, mass variation of 0.9–2.2 % (CV) and acceptance values below 15.0 were reached depending on chosen process parameters. [ABSTRACT FROM AUTHOR]

Flucloxacillin is prescribed to treat skin infections but its highly bitter taste is poorly tolerated in children. This work describes the application of the D-optimal mixture experimental design to identify the optimal component ratio of flucloxacillin, Eudragit EPO and palmitic acid to prepare flucloxacillin taste-masked microparticles that would be stable to storage and would inhibit flucloxacillin release in the oral cavity while facilitating the total release of the flucloxacillin load in the lower gastrointestinal tract (GIT). The model predicted ratio was found to be very close to the stoichiometric equimolar component ratio, which supported our hypothesis that the ionic interactions among flucloxacillin, Eudragit EPO and palmitic acid underscore the polyelectrolyte complex formation in the flucloxacillin taste-masked microparticles. The excipient–drug interactions showed protective effects on the microparticle storage stability and minimised flucloxacillin release at 2 min in dissolution medium. These interactions had less influence on flucloxacillin release in the dissolution medium at 60 min. Storage temperature and relative humidity significantly affected the chemical stability of the microparticles. At the preferred storage conditions of ambient temperature under reduced RH of 23%, over 90% of the baseline drug load was retained in the microparticles at 12 months of storage. [ABSTRACT FROM AUTHOR]

It is extremely challenging to formulate age-appropriate flucloxacillin medicines for young children, because flucloxacillin sodium (FS) has a lingering, highly bitter taste, dissolves quickly in saliva, and requires multiple daily dosing at relatively large doses for treating skin infections. In this paper, we describe a promising taste-masked flucloxacillin ternary microparticle (FTM) formulation comprising FS, Eudragit EPO (EE), and palmitic acid (PA). To preserve the stability of the thermolabile and readily hydrolysed flucloxacillin, the fabrication process employed a non-aqueous solvent evaporation method at ambient temperature. Optimisation of the fabrication method using a mixture design approach resulted in a robust technique that generated stable and reproducible FTM products. The optimised method utilised only a single solvent evaporation step and minimal amounts of ICH class III solvents. It involved mixing two solution phases—FS dissolved in ethanol:acetone (1:4 v/v), and a combination of EE and PA dissolved in 100% ethanol—to give a ternary FS:EE:PA system in ethanol: acetone (3:1 v/v). Solvent evaporation yielded the FTMs containing an equimolar ratio of FS:EE:PA (1:0.8:0.6 w/w). The fabrication process, after optimisation, demonstrated robustness, reproducibility, and potential scalability. [ABSTRACT FROM AUTHOR]

The WHO Model List of Essential Medicines for Children (EMLc) has not been systematically revised in the last few years. We conducted a survey addressed to healthcare professionals prescribing, preparing, or administering medicines to children and a narrative review to identify problematic paediatric formulations or missing medicines in all therapeutic fields to inform the review of the EMLc in 2023. A total of 285 physicians (63%), 28 nurses (6%) and 142 pharmacists (31%), mostly working in the hospital setting, reported at least one problematic medicine. 290 medicines were reported as missing (completely or the child-appropriate formulation). The top three most mentioned were ciprofloxacin together with phenobarbital and omeprazole. 387 medicines were reported as problematic (34% were oral liquid formulations, 34% tablets, 18% parenteral preparations. Mostly of the products were antibacterials (27%), cardiovascular medicines (11%) and antivirals (11%). The obtained responses show the perspective of healthcare workers working around the world, particularly in the European region (25%), in the African region (24%), and in the Region of the Americas (19%), with limited representation from Northern Africa and the Middle East. Our results need to be analysed with the outputs of other ongoing works before specific products can enter the WHO-hosted Global Accelerator for Paediatric formulations network prioritisation process. Efforts to develop appropriate formulations for children should be accelerated so that the uncertainties associated with off-label drug preparation and use are minimised, and therapeutic benefits are optimised. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The WHO Model List of Essential Medicines for Children (EMLc) has not been systematically revised in the last few years. We conducted a survey addressed to healthcare professionals prescribing, preparing, or administering medicines to children and a narrative review to identify problematic paediatric formulations or missing medicines in all therapeutic fields to inform the review of the EMLc in 2023. A total of 285 physicians (63%), 28 nurses (6%) and 142 pharmacists (31%), mostly working in the hospital setting, reported at least one problematic medicine. 290 medicines were reported as missing (completely or the child-appropriate formulation). The top three most mentioned were ciprofloxacin together with phenobarbital and omeprazole. 387 medicines were reported as problematic (34% were oral liquid formulations, 34% tablets, 18% parenteral preparations. Mostly of the products were antibacterials (27%), cardiovascular medicines (11%) and antivirals (11%). The obtained responses show the perspective of healthcare workers working around the world, particularly in the European region (25%), in the African region (24%), and in the Region of the Americas (19%), with limited representation from Northern Africa and the Middle East. Our results need to be analysed with the outputs of other ongoing works before specific products can enter the WHO-hosted Global Accelerator for Paediatric formulations network prioritisation process. Efforts to develop appropriate formulations for children should be accelerated so that the uncertainties associated with off-label drug preparation and use are minimised, and therapeutic benefits are optimised.

The Paediatric Committee of the European Medicines Agency encourages research into medicinal products for children, in particular, the development of an age-appropriate formulation of captopril is required in the cardiovascular therapeutic area. The aim of this study was the development of a liquid formulation using nanoparticles based only on chitosan and cellulose acetate phthalate containing captopril for the treatment of hypertension, heart failure and diabetic nephropathy in paediatric patients. Nanoparticles were prepared by a nanoprecipitation method/dropping technique without using surfactants, whose use can be associated with toxicity. A range of different cellulose to chitosan weight ratios were tested. A good encapsulation efficiency (61.0 ± 6.5%) was obtained when a high chitosan concentration was used (1:3 ratio); these nanoparticles (named NP-C) were spherical with a mean diameter of 427.1 ± 32.7 nm, 0.17 ± 0.09 PDI and +53.30 ± 0.95 mV zeta potential. NP-C dispersion remained stable for 28 days in terms of size and drug content and no captopril degradation was observed. NP-C dispersion released 70% of captopril after 2 h in pH 7.4 phosphate buffer and NP-C dispersion did not have a cytotoxicity effect on neonatal human fibroblasts except at the highest dose tested after 48 h. As a result, chitosan/cellulose nanoparticles could be considered a suitable platform for captopril delivery in paediatrics for preparing solid/liquid dosage forms. [ABSTRACT FROM AUTHOR]

Spironolactone (SPL), a potent anti-aldosterone steroidal drug used to treat several diseases in paediatric patients (e.g., hypertension, primary aldosteronism, Bartter's syndrome, and congestive heart failure), is not available in child-friendly dosage forms, and spironolactone liquids have been reported to be unpalatable. Aiming to enhance SPL solubility in aqueous solution and overcome palatability, herein, the effects of (2-hydroxypropyl)-β-cyclodextrin (HP-β-CyD) were thoroughly investigated on solubilisation in water and on masking the unpleasant taste of SPL in vivo. Although the complexation of SPL with HP-β-CyD was demonstrated through phase solubility studies, Job's plot, NMR and computational docking studies, our in vivo tests did not show significant effects on taste aversion. Our findings, on the one hand, suggest that the formation of an inclusion complex of SPL with HP-β-CyD itself is not necessarily a good indicator for an acceptable degree of palatability, whereas, on the other hand, they constitute the basis for investigating other cyclodextrin-based formulations of the poorly water-soluble steroidal drug, including solid dosage forms, such as spray-dried powders and orodispersible tablets. [ABSTRACT FROM AUTHOR]

Development of age appropriate medicines for children is one of the major challenge of our century. Historically, research of new paediatric drugs has been neglected due to poor industrial interest and limited public and private investments. The ID-EPTRI project is aimed to bridge the existing gaps in the paediatric medicine that stop the progress, from the early stage drug development phases to be translated into paediatric use of medicines, through a new paediatric Research Infrastructure. To reach this goal, EPTRI has developed and disseminated a survey in order to identify the gaps and map the competences of the excellence of the paediatric research in pan-European countries that will be the potential service providers of the new Research Infrastructure. EPTRI will network all the available competences and technologies useful to the paediatric research, creating an open science space allowing top-level researchers to work together.

Graphical abstract Abstract Transdermal drug delivery offers several attractive advantages over the traditional oral and parenteral routes. Particularly, in case of paediatric patients, it helps to overcome the issues specific to this population, such as difficulty in swallowing and palatability of oral medicines as well as fear and pain associated with needles. However, due to the formidable barrier characteristic of the stratum corneum, it fails in the effective systemic delivery of broad range of therapeutic molecules, especially macromolecules and genetic material. Over the last two decades, microneedle technology has been portrayed as a strategy to infringe the stratum corneum, in a minimally invasive manner, and enable the successful passage of molecules by creating transient channels across the skin. There has been an exponential surge in the number of studies exploring the design, development and fabrication of microneedles. This article reviews the evolution of microneedle technology and provides a comprehensive summary of microneedle research to date. It provides a detailed overview of the microneedle types, advanced fabrication strategies including the biodegradability and compatibility of the new materials used in fabrication. Research on microneedle-mediated paediatric drug delivery as well as insights on the application of this novel technology has been discussed. The up-to-date progress in clinical translation of microneedles and the regulatory requirements for their commercialization are highlighted along with a brief perspective on the future prospects of microneedle-mediated paediatric drug delivery. This review proposes that advanced research can further contribute to the improved therapeutic efficiency of microneedle-based delivery of numerous molecules, which are otherwise difficult to administer via the conventional transdermal delivery mechanisms. [ABSTRACT FROM AUTHOR]

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 (SympfinyTM, 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.

The purpose of this study was to develop an oral paediatric formulation of budesonide (BUD) for the treatment of inflammatory bowel disease. A formulation realized as microspheres using the prilling/vibration technique is proposed as an innovative drug delivery system ensuring BUD-specific colonic release in response to different triggers, such as pH, transit time, and resident microbiota. BUD, or the inclusion complex BUD/hydroxypropyl-β-cyclodextrin, was loaded into microspheres consisting of different ratios of alginate, Eudragit® FS 30D, with or without inulin. Sixteen formulations are produced that show high yields and encapsulation efficiencies, ensuring a homogenous distribution of BUD into the matrix. Microsphere diameters of <655 μm and promising flow properties make these systems suitable for oral administration to children. Swelling and drug release studies in simulated gastrointestinal fluid are used to demonstrate the response of microspheres to time and pH triggers. Studies in faecal medium highlight that drug release from microspheres with inulin is also influenced by microbiota. [ABSTRACT FROM AUTHOR]

In the process of implementation and innovation of paediatric dosage forms, buccal films for transmucosal administration of drug represent one of the most interesting approach. In fact, films are able to provide an extended duration of activity allowing minimal dosage and frequency and offer an exact and flexible dose, associated with ease of handling. The objective of the present study was to develop polymeric films for the sustained release of ondansetron hydrochloride, a selective inhibitor of 5-HT 3 receptors indicated in paediatrics for the prevention and treatment of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy and postoperatively. Films were prepared by casting and drying of aqueous solutions containing different weight ratios of hydroxypropylmethylcellulose (HPMC) with chitosan (CH) or sodium hyaluronate (HA) or gelatin (GEL) and characterized for their physico-chemical and functional properties. The presence of HA, GEL and CH did not improve the mucoadhesive properties of HPMC film. The inclusion of GEL and CH in HPMC film increased in vitro drug release with respect to the inclusion of HA, although films containing HA showed the highest water uptake. Moreover in agreement with the release behaviour, the inclusion of CH and GEL provided higher drug permeation through porcine buccal mucosa with respect to HPMC film and ensured linear permeation profiles of drug. [ABSTRACT FROM AUTHOR]

[Display omitted] Selecting the appropriate formulation and solubility-enabling technology for poorly water soluble drugs is an essential element in the development of formulations for paediatric patients. Different methodologies and structured strategies are available to select a suitable approach and guide formulation scientists for development of adult formulations. However, there is paucity of available literature for selection of technology and overcoming the challenges in paediatric formulation development. The need for flexible dosing, and the limited knowledge of the safety of many formulation excipients in paediatric subjects, impose significant constraints and in some instances require adaptation of the approaches taken to formulating these drugs for the adult population. Selection of the best drug delivery system for paediatrics requires an efficient, systematic approach that considers a drug's physical and chemical properties and the targeted patient population's requirements. This review is a step towards development of a strategy for the design of solubility enhancing paediatric formulations of highly insoluble drugs. The aim of this review is to provide an overview of different approaches and strategies to consider in order to assist development of paediatric formulation for poorly water-soluble drugs with the provision of examples of some marketed products. In addition, it provides recommendations to overcome the range of challenges posed by these strategies and adaptations of the adult approach/product presentation required to enable paediatric drug development and administration. [ABSTRACT FROM AUTHOR]

[Display omitted] Many medicines are only available in solid dosage forms suitable for adults, and extemporaneous compounding is required to prepare formulations for children. However, this common practice often results in inaccurate dosing and unpleasant taste, reducing the medication adherence. Here, we report the development of a new method to prepare and compound child-friendly oral formulations based on a liposomal multilamellar vesicle (MLV) platform. MLVs composed of a phospholipid (DSPC) and cholesterol (55/45, molar ratio) were prepared using the standard thin film hydration method with 300 mM citric acid (pH 2), followed by an addition of aqueous sodium carbonate to adjust the exterior pH to 8–10 for creating a transmembrane pH gradient. Weak-base drugs, such as chloroquine (CQ) and hydroxychloroquine (HCQ), could be actively and completely loaded into the MLVs at a drug-to-lipid ratio of 15–20 wt%. This technique formulated weak-base drugs from the powder or tablet form into a liquid preparation, and the complete drug encapsulation would prevent contact between the drug molecules and the taste buds. The gradient MLV formulation could be preserved by lyophilization and stored at room temperature for at least 8 weeks. Upon reconstitution with water, the MLV formulation could completely encapsulate CQ at 20 wt%, which was comparable to the freshly prepared MLVs. The CQ-loaded MLV formulation could be stored at 4 °C for 2 weeks without drug leakage. In vitro release studies indicated that MLV could retain CQ in the simulated saliva, but released up to 50% and 30% of the drug in the simulated gastric and intestinal fluids, respectively. The orally delivered MLV-CQ formulation displayed higher CQ absorption in mice, with a 2-fold increase in the area under the curve (AUC) of the plasma profile compared to CQ solution. Our data suggest that the new MLV method could serve as a platform to prepare child-friendly oral formulation for weak-base drugs. [ABSTRACT FROM AUTHOR]

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Abstract: Fixed-dose combinations of artesunate and amodiaquine hydrochloride provide challenges in product development due to the incompatibility of the two agents. This is particularly critical for paediatric preparations which can often be presented in liquid form. The studies reported in this article aimed to develop an understanding of the factors responsible for this incompatibility, whilst assessing the feasibility of developing a stable paediatric formulation. The stability characteristics of fast-disintegrating granular formulations containing intimate mixtures of both agents and single agent granules blended prior to production of unit doses were therefore studied under a range of storage conditions. The granular products remained stable over the 3-month period under stressed accelerated conditions, in contrast to control samples containing both drugs in combined granular form, which demonstrated reductions in artesunate content at elevated humidity. It was hypothesized that loss of active agent content for artesunate was accelerated by access to the water of crystallization of amodiaquine as demonstrated by the more facile dehydration of amodiaquine when a mixture of the two agents was analysed by differential scanning calorimetry (DSC). It was therefore concluded that a stable, versatile paediatric preparation of the two drugs could be prepared by blending pre-formulated granules containing the individual constituents rather than producing a combined granule comprising intimate mixtures of the two agents. [Copyright &y& Elsevier]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Exposure to bosentan was lower in paediatric pulmonary arterial hypertension (PAH) patients treated with the marketed adult formulation at a dose of about 2 mg kg−1 when compared with adult PAH patients. • In healthy adult subjects, bosentan pharmacokinetics are less than dose-proportional at doses of ≥500 mg. WHAT THIS STUDY ADDS • The pharmacokinetics of a new paediatric bosentan formulation were characterized in paediatric PAH patients. • The level of exposure to bosentan as observed in adult PAH patients cannot be reached in paediatric patients with b.i.d. dosing. • In paediatric PAH patients, nondose-proportional pharmacokinetics of bosentan occur at lower doses when compared with healthy adult subjects. AIM To show equivalent bosentan exposure in paediatric patients with pulmonary arterial hypertension (PAH) when compared with a cohort of historical controls of adult PAH patients using a newly developed paediatric formulation. METHODS Thirty-six paediatric PAH patients were enrolled in this multicentre, prospective, open-label, noncontrolled study and treated for 4 weeks with bosentan 2 mg kg−1 b.i.d. and then for 8 weeks with 4 mg kg−1 b.i.d. Blood samples were taken for pharmacokinetic purposes. Exploratory efficacy measurements included World Health Organization (WHO) functional class and parent's and clinician's Global Clinical Impression scales. RESULTS Comparing children with a historical group of adults, the geometric mean ratio (90% confidence interval) of the area under the plasma concentration–time curve was 0.54 (0.37, 0.78), i.e. children had lower exposure to bosentan than adults. Bosentan concentrations following doses of 2 and 4 mg kg−1 were similar. Improvements in WHO functional class and the Global Clinical Impression scales occurred mainly in bosentan-naive patients, whereas the rare worsenings occurred in patients already on bosentan prior to study initiation. The paediatric formulation was well accepted and bosentan well tolerated in this study. No cases of elevated liver enzymes or anaemia were reported. CONCLUSIONS Exposure to bosentan, as shown comparing the results from this study with those from a study in adults, was different in paediatric and adult PAH patients. Since FUTURE-1 and past studies suggest a favourable benefit–risk profile for bosentan at 2 mg kg−1 b.i.d., this dose is recommended for children with PAH. The new paediatric formulation was well tolerated. [ABSTRACT FROM AUTHOR]

A combination of amoxycillin and clavulanic acid 4:1 was administered to 35 children (aged 2 to 10 years) with infections. The combination was administered orally as a suspension, every 8 h for 5 to 7 days. Sixteen children (aged 2 to 5 years), received 125 mg amoxycillin and 31.25 mg clavulanic acid, and 19 (6 to 10 years) received 250 mg amoxycillin and 62.5 mg clavulanic acid per dose. Following the first dose serum concentrations of amoxycillin and clavulanic acid were determined by microbiological assay. In the younger group receiving the lower dosage (mean: amoxycillin 9.11 mg/kg and clavulanic acid 2.34 mg/kg), the mean peak concentration of amoxycillin was 3.5 mg/l and of clavulanic acid 1.2 mg/l, occurring 1.32 h and 1.39 h, respectively, after administration. In the older group receiving the higher dosage (mean: amoxycillin 12.35 mg/kg and clavulanic acid 3.14 mg/kg) the mean peak serum level of amoxycillin was 4.0 mg/l and of clavulanic acid 1.3 mg/l, occurring 1.43 h and 1.23 h, respectively, after administration. The higher dose per kilogram body weight resulted in a higher peak serum concentration both of amoxycillin and clavulanic acid. The formulation was well tolerated by all the children and no serious side-effects were recorded. Treatment was considered clinically effective in all cases. [ABSTRACT FROM AUTHOR]

The potential of alternative routes of application compared to the traditional oral route is constantly growing. Especially in transmucosal applications for the oral cavity, easy accessibility is an attractive feature with many new opportunities. The combination of a minitablet and a buccal mucoadhesive carrier film has been shown to enable safe and accurate drug administration compared to semi-solid formulations currently available on the market. In order to investigate these so-called composite dosage forms in more detail, two different manufacturing methods were compared within this study to investigate the resulting properties. The formulation development of the minitablets containing lidocaine, complying with the compendial requirements, resulted in immediate release using both manufacturing methods (more than 80% lidocaine release after 3–4 min using direct incorporation, 7–8 min by the gluing method). Differences in morphology and drug migration behaviour could be observed. The directly incorporated minitablets revealed a twofold higher drug migration (1.5 mm) into the mucoadhesive shielding film within two weeks compared to the glued minitablets (0.8 mm). These findings enable a further optimization of the formulation depending on the duration of the application and the feasibility for the addressed patient population. [ABSTRACT FROM AUTHOR]

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 (SympfinyTM, 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. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a new solid paediatric formulation for propranolol hydrochloride (PR). This drug is used to treat various paediatric diseases, and recently received clearance to treat haemangioma. However, PR has a bitter salty taste that does not facilitate high rates of compliance among children, especially in liquid formulations. In addition, the solid formulations are designed for adults and often their dosage is not suitable for children that require a flexible dose based on their weight. Therefore, matrix microbeads of EUDRAGIT® E PO containing PR were manufactured to overcome these limitations. Nine different samples were prepared using the prilling-congealing technique with high yield. Using 2 nozzles, 300 and 450 μm (code n), the diameters obtained of microbeads (from 333 to 699 μm) were homogenous and appropriate to be swallowed by children. In this study, the ratio drug:matrix for the microbeads was also examined in detail: 1:25 (F 1), 1:15 (F 2) and 1:10 (F 3) in aqueous and tert-butyl alcohol/aqueous (code t) media. Most of the examined microbeads were characterized by high percentage of encapsulation efficiency (22–100%) and drug loading (22–77 mg of drug per g of matrix) effective for the administration of low and high doses of PR. SEM analysis revealed a matrix with a radial or a spongy structure, with numerous pores that generated soft floating microbeads in aqueous solution. Release studies confirmed a low release and dissolution of the drug in artificial saliva, mainly F 1n > F 1 > F 2nt , and a prompt dissolution in simulated gastric media. Finally, electronic tongue measurements revealed the ability of these formulations to mask the bitter drug taste, especially for the sample with a ratio 1:25 (F 1n and F 1). These samples were chemically and physically stable for six months. In conclusion, the projected microbeads F 1 , and F 1n reached the goal of the study, and could be proposed as new solid oral formulations dedicated to use by children. [ABSTRACT FROM AUTHOR]