Formulating SLMs as oral pulsatile system for potential delivery of melatonin to pediatric population.
The formulation development of melatonin (MLT) for infants and children with neurodevelopmental difficulties was fully investigated. This population have a higher prevalence of sleep disorders and present special challenges for drug administration and swallowing. To solve these issues, solid lipid microparticles (SLMs) were designed to obtain an oral flexible dosage form constituted by GRAS excipients and a free flow pulsatile delivery system for MLT, able to maintain its release through 8h. Three groups of SLMs were produced by spray congealing and characterized as regards particle size, morphology, flowability, solid state, drug content and release behavior. The SLMs manipulation with milk and yogurt and the MLT stability in these foods were also investigated. Microparticles with different excipient composition were selected to obtain a pulsatile release pattern over 8h. The final delivery platform displayed a prompt release from group I SLMs together with a lag phase of groups II and III SLMs, followed by a repeated MLT release from group II and a prolonged MLT release related to the last group. Finally, MLT was compatible and stable in milk and yogurt suggesting that microparticles sprinkled into food is acceptable for MLT administration to children unable to swallow capsules or tablets.
Department of Pharmacy and Biotechnology, University of Bologna, Via San Donato 19/2, Bologna 40127, Italy. Electronic address: beatrice.albertini@unibo.it.
Beatrice
B
Albertini
Department of Pharmacy and Biotechnology, University of Bologna, Via San Donato 19/2, Bologna 40127, Italy.
Marcello
M
Di Sabatino
Department of Pharmacy and Biotechnology, University of Bologna, Via San Donato 19/2, Bologna 40127, Italy.
Cecilia
C
Melegari
Department of Pharmacy and Biotechnology, University of Bologna, Via San Donato 19/2, Bologna 40127, Italy.
Nadia
N
Passerini
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002648:Child; D002675:Child, Preschool; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D018565:Food-Drug Interactions; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000737:chemistry*; D007223:Infant; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008550:Melatonin / Q000008:administration & dosage* / Q000737:chemistry*; D008892:Milk / Q000737:chemistry; D010316:Particle Size; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D015014:Yogurt
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D006993:Hypnotics and Sedatives; D008055:Lipids; D008550:Melatonin
Dose flexibility; Melatonin; Oral pediatric formulation; Solid-lipid microparticles; Spray congealing; Stability in food