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 enhancing the acceptability of paediatric pharmaceutical formulations. Solid oral dosage forms (SODF), especially multiparticulates, are being considered as an alternative to liquid formulations, but they may compromise palatability when large volumes are required for dosing. We hypothesised that a binary mixture of multiparticulates for paediatric use, designed to increase the formulation maximum packing fraction, could reduce the viscosity of the mixture in soft food and facilitate swallowing. 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 for multi-particulate formulations, i.e., pellets (350 and 700 µm particles), minitablets (MTs, 1.8 mm), and their binary mixtures (BM), by evaluating oral swallowing time, the percentage of particles swallowed, and post-swallow residues. We also conducted a systematic analysis of the effect of the administration method, bolus volume, carrier type, particle size, and particle volume fraction on pellets swallowability. The results demonstrated that the introduction of pellets affected the flowing ability of the carriers, increasing shear viscosity. The size of the pellets did not appear to influence particle swallowability but raising the particle volume fraction (v.f.) above 10% resulted in a decrease in the percentage of particles swallowed. At v.f. 0.4, pellets were easier to swallow (+ 13.1%) than MTs, being the administration method used highly dependent on the characteristics of the multi-particulate formulation under consideration. Finally, mixing MTs with only 24% of pellets improved particle swallowability, achieving swallowing levels similar to those of pellets alone. Thus, combining SODF, i.e., MTs and pellets, improves MT swallowability, and offers new possibilities for adjusting product palatability, being particularly attractive for combination products.

A novel soft robotic pediatric in vitro swallowing device to gain insights into the swallowability of mini-tablets.

Soft robotics could help providing a better understanding of the mechanisms underpinning the swallowability of solid oral dosage forms (SODF), especially by vulnerable populations such as the elderly or children. In this study a novel soft robotic in vitro device is presented, the Pediatric Soft Robotic Tongue (PSRT), inspired by the literature data on the anatomy and physiology of a 2-year-old child. Multi-particulate oral formulations (i.e., mini-tablets (MT)) were considered, including different scenarios such as SODF carrier (i.e., soft-food, liquid), administration methods, SODF size and volume fraction. In vitro results showed that semi-solid foods like yoghurt and apple puree (shear viscosity above âˆ¼ 150 mPa.s at γ̇ = 50 s-1, and its yield stress up to âˆ¼ 5 Pa) may be considered more suitable than thin liquids (i.e., xanthan gum 0.25 %) for swallowing MT. However, the reduction of MT size did not bring any benefit in terms of swallowability in the range studied. Regarding the administration method, spreading MT on top of a teaspoon full of carrier should be preferred over mixing MT with the carrier or placing MT on the tongue first to favour their swallowability. Finally, and under the in vitro conditions studied using yoghurt as carrier, it would be possible to increase the volume fraction of SODF up to 0.20 without influencing swallowability according to the three parameters evaluated (% of MT swallowed, bolus velocity, and post-swallow residues). These results should help to design more focused sensory and/or clinical tests to improve product formulation and patient acceptability.