RESUMO
OBJECTIVES: To assess the acceptability and swallowability of several minitablets when administered as a unit dose compared with an equivalent dose of syrup in children aged 6 months to 5 years. STUDY DESIGN: The acceptability and swallowability of multiple drug-free minitablets in comparison with glucose syrup was assessed in 372 children of 2 age groups (186 in age group 1 [6-23 months of age] and 186 in age group 2 [2-5 years of age]) in a randomized, 3-way, single administration cross-over study. Age group 1 received 25 minitablets, 100 minitablets, and 5 mL syrup. Age group 2 received 100 minitablets, 400 minitablets, and 10 mL syrup. RESULTS: Superiority was demonstrated in age group 1 for acceptability (25 minitablets, P < .017; 100 minitablets, P < .0001) and swallowability (25 minitablets and 100 minitablets, both P < .0001) compared with syrup. In age group 2, noninferiority of acceptability was found only for 400 minitablets (P < .0003), not for 100 minitablets. Subgroup analysis revealed a strong sequential effect. For swallowability, noninferiority could be demonstrated for 100 minitablets (P < .01) but not for 400 minitablets. CONCLUSIONS: Administration of ≥25 minitablets is well-tolerated, feasible, and safe in children aged from 6 months, and was superior to the equivalent dose of syrup. Children aged >1 year accept ≤400 minitablets even better than the equivalent dose of syrup. Minitablets open the perspective for introducing small-sized solid drug formulations for all children, thus, further shifting the paradigm from liquid toward small-sized solid drug formulations. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00008843.
Assuntos
Deglutição/fisiologia , Aceitação pelo Paciente de Cuidados de Saúde , Comprimidos/administração & dosagem , Administração Oral , Química Farmacêutica/métodos , Pré-Escolar , Estudos Cross-Over , Formas de Dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Preparações Farmacêuticas , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
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.