Elsevier

The Journal of Pediatrics

Volume 163, Issue 6, December 2013, Pages 1728-1732.e1
The Journal of Pediatrics

Original Article
Favorable Acceptance of Mini-Tablets Compared with Syrup: A Randomized Controlled Trial in Infants and Preschool Children

https://doi.org/10.1016/j.jpeds.2013.07.014Get rights and content

Objective

To evaluate acceptability of 2 mm solid dosage forms (mini-tablets) as an alternative administration modality in young children in comparison with syrup.

Study design

Three hundred six pediatric in- and outpatients aged 6 months-5 years (51 in each of 6 age groups) were recruited. An open, randomized cross-over study was conducted to compare acceptability and capability to swallow 2 mm uncoated or coated mini-tablets vs 3 mL syrup.

Results

In the overall patient population of 306 children, the acceptability of uncoated mini-tablets was superior to syrup (difference in proportions 14.8%, 95% CI 10.2-19.4; P < .0001). In line with this finding, the level of capability to swallow was higher for uncoated mini-tablets compared with syrup as well (difference in proportions 12.3%, 95% CI 5.4-19.3; P = .0008). All 3 pharmaceutical formulations were well tolerated, and none of the 306 children inhaled or coughed because of the syrup or the uncoated mini-tablet; only 2 of the 306 children (both in age group 0.5-1 year) coughed because of the coated mini-tablet, in both cases without clinical relevance.

Conclusions

Mini-tablets are a valuable alternative to syrup for children 6 months-6 years of age and are more acceptable compared with liquid formulation. Regulatory bodies such as Food and Drug Administration and European Medicine Agency are encouraged to take our data into account for guideline updates and future drug approval processes.

Section snippets

Methods

This trial was a single-center, randomized, open (unblinded) cross-over study. Participants sequentially received 3 oral drug-free formulations (uncoated and coated mini-tablets and syrup) and were randomized to one of 6 possible sequences. The study was conducted according to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use guideline for Good Clinical Practice with a risk-adapted level of monitoring, adequate patient

Results

Participants were recruited between February and June 2011. Data of all 306 participants were evaluated; 127 of 306 (41.5%) participants were female, ranging from 29.4% (age 1 to 2 years) to 54.9% (age 2 to 3 years).

As primary endpoint of this study, the acceptability of the uncoated 2 mm mini-tablet was significantly higher compared with glucose syrup (difference in proportions 14.8%, 95% CI 10.2-19.4; P < .0001) for the entire study population. All following data are secondary endpoints. The

Discussion

The study was designed as a confirmatory (uncoated mini-tablets) trial but also as an exploratory (film-coated mini-tablets) trial to assess the use of mini-tablets as an alternative drug dosage form for preschool children. Based on the significantly higher acceptability of uncoated mini-tablets compared with syrup in this study, which was greater than expected from our pilot study, we conclude that uncoated mini-tablets are a new therapeutic alternative to liquid formulations for infants and

References (14)

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    To avoid unintended chewing, which can lead to noncompliance with medication due to unpleasant taste, safety concerns, and decreased drug product efficacy, the maximum size of multiparticulate must be determined. Numerous studies have shown that children in preschool (up to the age of six) and even infants (up to the age of six months) can safely swallow particles smaller than three millimetres (Klingmann et al., 2013; Kluk et al., 2015; Spomer et al., 2012). On the other hand, newborns allow swallowing only liquids before the age of five months.

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The authors declare no conflicts of interest.

Registered with the German Clinical Trials Register: DRKS00000432.

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