Paediatric Solid Oral Dosage Forms for Combination Products: Improving In Vitro Swallowability of Minitablets Using Binary Mixtures with Pellets

There is a growing interest in determining and improving the acceptability of solid oral dosage forms (SODF) in paediatric populations. Combination products can be an interesting solution to combine two active pharmaceutical ingredients. This study shows that binary mixture of paediatric SODF could enhance formulation swallowability and palatability. Using the Paediatric Soft Robotic Tongue (PSRT) – an in vitro device inspired by the anatomy and physiology of 2-year-old children – we investigated the oral phase of swallowing of multi-particulate formulations, i.e., pellets (350 and 700 µm particles), minitablets (MTs, 1.8 mm), and their binary mixtures (BM), by measuring the oral swallowing time, the fraction of particles swallowed, and the post-swallow residues.

The effects of the feeding method, bolus volume, type of carrier, particle size, and particle volume fraction on pellets swallowability were also systematically studied. The flowing ability of the carriers was affected by the addition of pellets: shear viscosity generally increased, yet little effect was observed on their shear thinning behaviour. Xanthan gum-based solutions achieved excellent swallowing levels for pellets (≥ 75 %), especially at high concentrations, i.e., 0.5 and 1%, favouring pellets transport without affecting post-swallow residues. Particle swallowability does not appear to be influenced by pellet size but increasing particle volume fraction (v.f.) above 10% reduced the percentage of particles swallowed.

At v.f. 0.4, pellets were easier to swallow (+ 13.1%) than MTs, being the administration method used strongly dependent of the characteristics of the multi-particulate formulation under study. To enhance MT swallowability, a novel approach involving MT-pellets binary mixtures was explored, whereby the maximum solid packing fraction of the formulation was increased. Mixing MTs with only 24% of pellets improved particle swallowability, achieving swallowing levels similar to those of pellets alone. Therefore, a combination of SODF, i.e., MTs and pellets, improved particle swallowability, opening the door to new ways of modulating product palatability, particularly attractive for combination products.

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Following excipients are mentioned in the study besides other: Cellets

Alejandro Avila-Sierra, Anaïs Lavoisier, Timpe Carsten, Peter Kuehl, Leonie Wagner, et al.. Paediatric
Solid Oral Dosage Forms for Combination Products: Improving In Vitro Swallowability of Minitablets
Using Binary Mixtures with Pellets. 2023. ffhal-03938323f