Introduction: Most conventional drug delivery systems are not acceptable for pediatric patients as they differ in their developmental status and dosing requirements from other subsets of the population. Technology platforms are required to aid the development of age-appropriate medicines to maximize patient acceptability while maintaining safety, efficacy, accessibility and affordability. Areas covered: The current approaches and novel developments in the field of age-appropriate drug delivery for pediatric patients are critically discussed including patient-centric formulations, administration devices and packaging systems. Expert opinion: Despite the incentives provided by recent regulatory modifications and the efforts of formulation scientists, there is still a need for implementation of pharmaceutical technologies that enable the manufacture of licensed age-appropriate formulations. Harmonization of endeavors from regulators, industry and academia by sharing learning associated with data obtained from pediatric investigation plans, product development pathways and scientific projects would be the way forward to speed up bench-to-market age appropriate formulation development. A collaborative approach will benefit not only pediatrics, but other patient populations such as geriatrics would also benefit from an accelerated patient-centric approach to drug delivery.

Multiparticulate formulations are composed of multiple solid dosage units which can be administered directly to the mouth or sprinkled on food. Oral grittiness (i.e. rough mouthfeel) may arise from the presence of particles in the mouth, limiting palatability. In this work, multiparticulate formulations were prepared by dispersion of spherical granules into orange flavoured vehicles thickened with hypromellose (HPMC) at different viscosities in order to assess oral perception of grittiness by a panel of thirty adults through direct scaling on a 100mm visual analogue scale. The effect of formulation factors such as particle size (90, 127, 263μm), amount of particles per 10ml (0.25, 0.50, 1.00g) and viscosity of the vehicle (0.08, 0.43, 2.80Pas) were investigated. Grittiness was increasingly perceived with increasing amount and size of particles. Increasing viscosity of the administration media had a masking effect on the perception of particles. Less gritty samples were generally regarded as 'more pleasant' by the participants of the study. However, samples dispersed in thickened vehicles seemed to be less preferred despite being less gritty; which could be ascribed to an unpleasant mouthfeel of the vehicle. In the design of multiparticulate formulations acceptable for a targeted patient group all these formulation factors will need to be considered and optimised.

Following an array of optimization experiments, two series of electrospun polyvinylpyrrolidone (PVP) fibers were prepared. One set of fibers contained various loadings of indomethacin, known to form stable glasses, and the other griseofulvin (a poor glass former). Drug loadings of up to 33% w/w were achieved. Electron microscopy data showed the fibers largely to comprise smooth and uniform cylinders, with evidence for solvent droplets in some samples. In all cases, the drug was found to exist in the amorphous physical state in the fibers on the basis of X-ray diffraction and differential scanning calorimetry (DSC) measurements. Modulated temperature DSC showed that the relationship between a formulation's glass transition temperature (Tg) and the drug loading follows the Gordon-Taylor equation, but not the Fox equation. The results of Gordon-Taylor analysis indicated that the drug/polymer interactions were stronger with indomethacin. The interactions between drug and polymer were explored in more detail using molecular modeling simulations and again found to be stronger with indomethacin; the presence of significant intermolecular forces was further confirmed using IR spectroscopy. The amorphous form of both drugs was found to be stable after storage of the fibers for 8 months in a desiccator (relative humidity <25%). Finally, the functional performance of the fibers was studied; in all cases, the drug-loaded fibers released their drug cargo very rapidly, offering accelerated dissolution over the pure drug.

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 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.

Co-processed excipients may enhance functionality and reduce drawbacks of traditional excipients for the manufacture of tablets on a commercial scale. The following study aimed to characterise a range of co-processed excipients that may prove suitable for dispersible tablet formulations prepared by direct compression. Co-processed excipients were lubricated and compressed into 10.5-mm convex tablets using a Phoenix compaction simulator. Compression profiles were generated by varying the compression force applied to the formulation and the prepared tablets were characterised for hardness, friability, disintegration and fineness of dispersion. Our data indicates that CombiLac, F-Melt type C and SmartEx QD100 were the top 3 most suitable out of 16 co-processed excipients under the conditions evaluated. They exhibited good flow properties (Carr's index ˂ 20), excellent tabletability (tensile strength > 3.0 MPa at 0.85 solid fraction), very low friability (< 1% after 15 min), rapid disintegration times (27-49 s) and produced dispersions of ideal fineness (< 250 μm). Other co-processed excipients (including F-Melt type M, Ludiflash, MicroceLac, Pharmaburst 500 and Avicel HFE-102) may be appropriate for dispersible tablets produced by direct compression providing the identified disintegration and dispersion risks were mitigated prior to commercialisation. This indicates that robust dispersible tablets which disintegrate rapidly could be manufactured from a range of co-processed excipients.

Paediatrics and geriatrics both represent highly heterogenous populations and require special consideration when developing appropriate dosage forms. This paper discusses similarities, differences and considerations with respect to the development of appropriate medicine formulations for paediatrics and geriatrics. Arguably the most significant compliance challenge in older people is polypharmacy, whereas for children the largest barrier is taste. Pharmaceutical technology has progressed rapidly and technologies including FDCs, multi-particulates and orodispersible dosage forms provide unprecedented opportunities to develop novel and appropriate formulations for both old and new drugs. However, it is important for the formulation scientists to work closely with patients, carers and clinicians to develop such formulations for both the paediatric and geriatric population.

Flexible dosing and ease of swallowing are key factors when designing oral drug delivery systems for paediatric and geriatric populations. Multi-particulate oral dosage forms can offer significant benefits over conventional capsules and tablets. This study proposes the use of an in vitro model to quantitatively investigate the swallowing dynamics in presence of multi-particulates. In vitro results were compared against sensory tests that considered the attributes of ease of swallowing and post-swallow residues. Water and hydrocolloids were considered as suspending vehicles, while the suspended phase consisted of cellulose pellets of two different average sizes. Both in vivo and in vitro tests reported easier swallow for smaller multi-particulates. Besides, water thin liquids appeared not optimal for complete oral clearance of the solids. The sensory study did not highlight significant differences between the levels of thickness of the hydrocolloids. Conversely, more discriminant results were obtained from in vitro tests, suggesting that a minimum critical viscosity is necessary to enable a smooth swallow, but increasing too much the carrier concentration affects swallowing negatively. These results highlight the important interplay of particle size and suspending vehicle rheology and the meaningful contribution that in vitro methods can provide to pre-screening multi-particulate oral drug delivery systems before sensory evaluation.