Viviane Klingmann1, Christoph Emanuel Pohly2, Thomas Meissner2, Ertan Mayatepek2, Andreas Möltner3, Kathrin Flunkert4, Jörg Breitkreutz5, Hans Martin Bosse2. 1. Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany. Electronic address: Viviane.klingmann@med.uni-duesseldorf.de. 2. Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany. 3. Center of Excellence for Assessment in Medicine, Medical Faculty, University Heidelberg, Im Neuenheimer Feld 346, 69120 Heidelberg, Germany. 4. M.A.R.C.O. Institute for Clinical Research and Statistics, Schirmerstrasse 71, 40211 Düsseldorf, Germany. 5. Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
Abstract
OBJECTIVES: Reliable pediatric pharmacotherapy in all age groups requires the availability of age-appropriate drug administration. Orodispersible films (ODF) are a promising pediatric oral dosage form. ODFs would meet relevant targets: one dosage form matching the full range of pediatric patients, a minimum of non-toxic excipients, a stable drug formulation easily to be produced. However, there is a lack of reliable data on ODFs' acceptability, swallowability and palatability, especially in young children. The primary objective was to demonstrate non-inferiority in acceptability of a drug-free ODF in comparison to glucose syrup in children aged below one year. Secondary objectives were swallowability and palatability of the two formulations. STUDY DESIGN: The study was performed in an open, randomized, two-way cross-over design with three age groups: 2-28 days, 29 days-5 months, 6-12 months. 150 children (N = 50 per age group) were randomized to the order of receiving the ODF (2 × 3 cm) and age-adapted amounts of glucose syrup (0.5-3 mL). Deglutition and swallowing were assessed according to predefined evaluation criteria. The application of the formulations was documented by video to evaluate the palatability. RESULTS: The primary objective was confirmed: Non-inferiority of the acceptability of an ODF compared to syrup was demonstrated, even superiority of the ODF was shown (p < 0.0001). The secondary endpoints demonstrated positive results including the superior swallowability of the ODF in comparison to syrup (p < 0.0001). The palatability assessments were in favor of the ODF. CONCLUSION: ODFs are a promising and safe alternative to liquid formulations, even for children of very young ages.
RCT Entities:
OBJECTIVES: Reliable pediatric pharmacotherapy in all age groups requires the availability of age-appropriate drug administration. Orodispersible films (ODF) are a promising pediatric oral dosage form. ODFs would meet relevant targets: one dosage form matching the full range of pediatric patients, a minimum of non-toxic excipients, a stable drug formulation easily to be produced. However, there is a lack of reliable data on ODFs' acceptability, swallowability and palatability, especially in young children. The primary objective was to demonstrate non-inferiority in acceptability of a drug-free ODF in comparison to glucose syrup in children aged below one year. Secondary objectives were swallowability and palatability of the two formulations. STUDY DESIGN: The study was performed in an open, randomized, two-way cross-over design with three age groups: 2-28 days, 29 days-5 months, 6-12 months. 150 children (N = 50 per age group) were randomized to the order of receiving the ODF (2 × 3 cm) and age-adapted amounts of glucose syrup (0.5-3 mL). Deglutition and swallowing were assessed according to predefined evaluation criteria. The application of the formulations was documented by video to evaluate the palatability. RESULTS: The primary objective was confirmed: Non-inferiority of the acceptability of an ODF compared to syrup was demonstrated, even superiority of the ODF was shown (p < 0.0001). The secondary endpoints demonstrated positive results including the superior swallowability of the ODF in comparison to syrup (p < 0.0001). The palatability assessments were in favor of the ODF. CONCLUSION: ODFs are a promising and safe alternative to liquid formulations, even for children of very young ages.
Keywords:
Acceptability; Drug administration; Drug dosage forms; Neonates and infants; Orodispersible film; Pediatric drug formulations; Swallowability