title: Acceptability of Uncoated Mini-Tablets in Neonates--A Randomized Controlled Trial.
abstract: 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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  German Clinical Trials Register (Deutsches Register Klinischer Studien [DRKS; germanctr.de]): DRKS00005609.
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Viviane
authors.initials: V
authors.lastname: Klingmann
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Seitz
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meissner
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Breitkreutz
authors.affiliation: Kompetenzzentrum für Prüfungen in der Medizin, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Moeltner
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Hans Martin
authors.initials: HM
authors.lastname: Bosse
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D003371:Cough; D018592:Cross-Over Studies; D003679:Deglutition; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D004364:Pharmaceutical Preparations; D011446:Prospective Studies; D015203:Reproducibility of Results; D013607:Tablets / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D004364:Pharmaceutical Preparations; D013607:Tablets