title: Development and characterization of crosslinked hyaluronic acid polymeric films for use in coating processes.
abstract: The aim of this work was to develop and characterize new hyaluronic acid-based responsive materials for film coating of solid dosage forms. Crosslinking of hyaluronic acid with trisodium trimetaphosphate was performed under controlled alkaline aqueous environment. The films were produced through casting process by mixing crosslinked or bare biopolymer in aqueous dispersion of ethylcellulose, at different proportions. Films were further characterized regarding morphology by scanning electron microscopy, robustness by permeation to water vapor transmission, and ability to hydrate in simulated gastric and intestinal physiological fluids. The safety and biocompatibility of films were assessed against Caco-2 and HT29-MTX intestinal cells. The permeation to water vapor transmission was favored by increasing hyaluronic acid content in the final formulation. When in simulated gastric fluid, films exhibited lower hydration ability compared to more extensive hydration in simulated intestinal fluids. Simultaneously, in simulated intestinal fluids, films partially lost weight, revealing ability for preventing drug release at gastric pH, but tailoring the release at higher intestinal pH. The physiochemical characterization suggests thermal stability of films and physical interaction between compounds of formulation. Lastly, cytotoxicity tests demonstrated that films and individual components of the formulations, when incubated for 4h, were safe for intestinal cells Overall, these evidences suggest that hyaluronic acid-based responsive films, applied as coating material of oral solid dosage forms, can prevent the premature release of drugs in harsh stomach conditions, but control the release it in gastrointestinal tract distal portion, assuring safety to intestinal mucosa.
authors.affiliation: Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Sgorla
authors.affiliation: i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB⿿Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Almeida
authors.affiliation: INEB⿿Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
authors.forename: Claudia
authors.initials: C
authors.lastname: Azevedo
authors.affiliation: Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil.
authors.forename: Ÿlcio Jose
authors.initials: ŸJ
authors.lastname: Bunhak
authors.affiliation: Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil; i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB⿿Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, Gandra, Portugal. Electronic address: bruno.sarmento@ineb.up.pt.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.affiliation: Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil; Departamento de Farmacologia e Terapêutica, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: Osvaldo Albuquerque
authors.initials: OA
authors.lastname: Cavalcanti
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000138:chemical synthesis* / Q000494:pharmacology; D011108:Polymers / Q000138:chemical synthesis* / Q000494:pharmacology; D014961:X-Ray Diffraction
chemical_list: D003432:Cross-Linking Reagents; D011108:Polymers; D006820:Hyaluronic Acid
keywords: Biopolymer; Ethylcellulose; Hyaluronic acid; Polymeric coating; Trisodium trimetaphosphate