Acceptability of Uncoated Mini-Tablets in Neonates--A Randomized Controlled Trial.

OBJECTIVE: To evaluate the suitability of drug-free solid dosage forms (2 mm mini-tablets) as an alternative administration modality in neonates in comparison with syrup. STUDY DESIGN: A total of 151 neonates (inpatients; aged 2-28 days; median 4 days) were recruited. An open, randomized, prospective cross-over study was conducted to compare the acceptability and swallowability of 2 mm uncoated mini-tablets compared with .5 mL syrup. RESULTS: All neonates (N = 151) accepted the uncoated mini-tablet as well as the syrup (both formulations 100%; 95% CI 97.6%-100.0%; primary objective). The level of swallowability of uncoated mini-tablets was not inferior (P < .0001), in fact even higher (difference in proportions 10.0%; 95% CI 1.37%-19.34%; P = .0315) compared with syrup. Both pharmaceutical formulations were well tolerated, and in none of the 151 neonates, serious adverse events occurred; particularly none of the neonates inhaled or coughed in either of the formulations. CONCLUSIONS: The administration of uncoated mini-tablets proved to be a valuable alternative to syrup for term neonates. Our data on neonates close the age gap of prior findings in toddlers and infants: uncoated mini-tablets offer the potential of a single formulation for all age groups. These findings further shift the paradigm from liquid toward small-sized solid drug formulations for children of all age groups, as the World Health Organization proposes. TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Klinischer Studien [DRKS; germanctr.de]): DRKS00005609.

Favorable acceptance of mini-tablets compared with syrup: a randomized controlled trial in infants and preschool children.

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.