title: Didanosine-loaded chitosan microspheres optimized by surface-response methodology: a modified "Maximum Likelihood Classification" approach formulation for reverse transcriptase inhibitors.
abstract: Didanosine-loaded chitosan microspheres were developed applying a surface-response methodology and using a modified Maximum Likelihood Classification. The operational conditions were optimized with the aim of maintaining the active form of didanosine (ddI), which is sensitive to acid pH, and to develop a modified and mucoadhesive formulation. The loading of the drug within the chitosan microspheres was carried out by ionotropic gelation technique with sodium tripolyphosphate (TPP) as cross-linking agent and magnesium hydroxide (Mg(OH)₂) to assure the stability of ddI. The optimization conditions were set using a surface-response methodology and applying the "Maximum Likelihood Classification", where the initial chitosan concentration, TPP and ddI concentration were set as the independent variables. The maximum ddI-loaded in microspheres (i.e. 1433 mg of ddI/g chitosan), was obtained with 2% (w/v) chitosan and 10% TPP. The microspheres depicted an average diameter of 11.42 μm and ddI was gradually released during 2 h in simulated enteric fluid.
authors.affiliation: Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Arthur Riedel, 275, Diadema 09972-270, Brazil.
authors.forename: Classius
authors.initials: C
authors.lastname: Ferreira da Silva
authors.affiliation: Department of Biotechnological Processes, School of Engineering Chemical, University of Campinas, Campinas 13083-970, Brazil; University of Tiradentes and Institute of Technology and Research, Av. Murilo Dantas 300, 49010-390 Aracaju, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Severino
authors.affiliation: Department of Biotechnological Processes, School of Engineering Chemical, University of Campinas, Campinas 13083-970, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Martins
authors.affiliation: Department of Biotechnological Processes, School of Engineering Chemical, University of Campinas, Campinas 13083-970, Brazil. Electronic address: lena@feq.unicamp.br.
authors.forename: Maria Helena A
authors.initials: MH
authors.lastname: Santana
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra (FFUC), Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; Center for Neuroscience and Cell Biology & Institute for Biomedical Imaging and Life Sciences (CNC-IBILI), University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: ebsouto@ff.uc.pt.
authors.forename: Eliana B
authors.initials: EB
authors.lastname: Souto
mesh_terms: D048271:Chitosan / Q000737:chemistry*; D016049:Didanosine / Q000008:administration & dosage / Q000737:chemistry*; D004304:Dosage Forms; D008863:Microspheres; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D013499:Surface Properties; D013678:Technology, Pharmaceutical
chemical_list: D004304:Dosage Forms; D018894:Reverse Transcriptase Inhibitors; D048271:Chitosan; D016049:Didanosine
keywords: Chitosan; Didanosine; Microspheres; Pharmacotherapy; Reverse transcriptase inhibitors; Sodium tripolyphosphate; Surface-response methodology