Viviane Klingmann1, Annika Seitz1, Thomas Meissner1, Jörg Breitkreutz2, Andreas Moeltner3, Hans Martin Bosse1. 1. Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Düsseldorf, Düsseldorf, Germany. 2. Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Düsseldorf, Germany. 3. Kompetenzzentrum für Prüfungen in der Medizin, Heidelberg, Germany.
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. 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 mmuncoated 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.
RCT Entities:
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.
Authors: Milica Bajcetic; Saskia N de Wildt; Michiel Dalinghaus; Jörg Breitkreutz; Ingrid Klingmann; Florian B Lagler; Anne Keatley-Clarke; Johannes Mpj Breur; Christoph Male; Ida Jovanovic; Andras Szatmári; László Ablonczy; Bjoern B Burckhardt; Willi Cawello; Karl Kleine; Emina Obarcanin; Lucie Spatenkova; Vanessa Swoboda; Marijke van der Meulen; Peter Wagner; Jennifer Walsh; Stephanie Läer Journal: Contemp Clin Trials Commun Date: 2019-06-08
Authors: Diana A van Riet-Nales; Alfred F A M Schobben; Herman Vromans; Toine C G Egberts; Carin M A Rademaker Journal: Arch Dis Child Date: 2016-03-15 Impact factor: 3.791