title: Optimization of Melatonin Dissolution from Extended Release Matrices Using Artificial Neural Networking.
abstract: BACKGROUND
  Efficacy of melatonin in treating sleep disorders has been demonstrated in numerous studies. Being with short half-life, melatonin needs to be formulated in extended-release tablets to prevent the fast drop of its plasma concentration. However, an attempt to mimic melatonin natural plasma levels during night time is challenging.
  
  
  METHODS
  In this work, Artificial Neural Networks (ANNs) were used to optimize melatonin release from hydrophilic polymer matrices. Twenty-seven different tablet formulations with different amounts of hydroxypropyl methylcellulose, xanthan gum and Carbopol®974P NF were prepared and subjected to drug release studies. Using dissolution test data as inputs for ANN designed by Visual Basic programming language, the ideal number of neurons in the hidden layer was determined trial and error methodology to guarantee the best performance of constructed ANN.
  
  
  RESULTS
  Results showed that the ANN with nine neurons in the hidden layer had the best results. ANN was examined to check its predictability and then used to determine the best formula that can mimic the release of melatonin from a marketed brand using similarity fit factor.
  
  
  CONCLUSIONS
  This work shows the possibility of using ANN to optimize the composition of prolonged-release melatonin tablets having dissolution profile desired.
authors.forename: D
authors.initials: D
authors.lastname: Martarelli
authors.affiliation: Department of Biomolecular Sciences, School of Pharmacy, University of Urbino, Piazza Rinascimento n°6, 61029, Urbino (PU), Italy. luca.casettari@uniurb.it.
authors.forename: L
authors.initials: L
authors.lastname: Casettari
authors.forename: K S
authors.initials: KS
authors.lastname: Shalaby
authors.forename: M E
authors.initials: ME
authors.lastname: Soliman
authors.forename: M
authors.initials: M
authors.lastname: Cespi
authors.forename: G
authors.initials: G
authors.lastname: Bonacucina
authors.forename: L
authors.initials: L
authors.lastname: Fagioli
authors.forename: D R
authors.initials: DR
authors.lastname: Perinelli
authors.forename: J K W
authors.initials: JK
authors.lastname: Lam
authors.forename: G F
authors.initials: GF
authors.lastname: Palmieri
mesh_terms: D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D008550:Melatonin / Q000008:administration & dosage / Q000737:chemistry*; D016571:Neural Networks, Computer; D012995:Solubility; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D008550:Melatonin