Evaluating the Acceptability, Swallowability, and Palatability of Film-Coated Mini-Tablet Formulation in Young Children: Results from an Open-Label, Single-Dose, Cross-Over Study

Abstract

Mini-tablets are advantageous over liquid formulations in overcoming challenges related to stability, taste, and dosage. This open-label, single-dose, cross-over study investigated the acceptability and safety of drug-free, film-coated mini-tablets in children aged 1 month–6 years (stratified: 4–6 years, 2–<4 years, 1–<2 years, 6–<12 months, and 1–<6 months), and their preference for swallowing either a high quantity of 2.0 mm or a low quantity of 2.5 mm diameter mini-tablets. The primary endpoint was acceptability derived from swallowability. The secondary endpoints were investigator-observed palatability, acceptability as a composite endpoint derived from both swallowability and palatability, and safety. Of 320 children randomized, 319 completed the study. Across all tablet sizes, quantities and age groups, acceptability rates based on swallowability were high (at least 87%). Palatability was rated as “pleasant/neutral” in 96.6% of children. The acceptability rates as per the composite endpoint were at least 77% and 86% for the 2.0 mm and 2.5 mm film-coated mini-tablets, respectively. No adverse events or deaths were reported. Recruitment in the 1–<6-months group was stopped early due to coughing—evaluated as “choked on” in three children. Both 2.0 mm and 2.5 mm film-coated mini-tablets are suitable formulations for young children.

Questionnaire Study to Investigate the Preferences of Children, Parents, and Healthcare Professionals for Different Formulations of Oral Medicinal Products

“…This preference was consistent among all stakeholders, despite some differences in formulation preferences of different stakeholders for the four age groups of pediatric patients. This very important result is in line with several other investigations and studies [ 8 , 9 , 10 , 11 , 12 , 14 , 15 , 16 , 17 , 18 , 23 ] and contrasts with the current practice of administering medicines to children aged 0–<6 y as a liquid formulation. As syrups or other liquid formulations might contain excipients with potential toxicological risks [ 35 ], a switch to alternative dosage forms could not only increase the acceptability but also improve the risk profile.…”

“…A number of studies have been performed investigating the acceptability of various formulations by more or less objective, validated-methodology-based investigations of swallowability and/or palatability in small children [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Interestingly, the current practice of liquid or syrup administration in children is considered to be unreliable, with significant under- or over-dosing [ 19 ].…”