Hidrogéis contendo nanocápsulas de dipropionato de betametasona e óleo de borragem: estudo de estabilidade em embalagem primária e permeação/penetração cutânea in vitro

• Ano de defesa: 2019
• Autor(a) principal: Funk, Nadine Lysyk
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; Análises Clínicas e Toxicológicas; UFSM; Programa de Pós-Graduação em Ciências Farmacêuticas; Centro de Ciências da Saúde
• Palavras-chave em Português: Ácido gama-linoleico; Semissólidos; Estabilidade; Material de embalagem; Oclusão; Permeação; Gamma-linoleic acid; Semisolid; Stability; Packaging material; Occlusion; Permeation; CNPQ::CIENCIAS DA SAUDE::FARMACIA
• Link de acesso: http://repositorio.ufsm.br/handle/1/21949

Corticosteroids and emollient substances (with high amounts of fatty acids as gama-linoleic acid) association is usually reported aiming the treatment of inflammatory skin diseases, such as atopic dermatitis. Topic formulations become interesting as an alternative route to deliver those drugs and minimize systemic adverse effects. Moreover, through nanotechnology it is possible to associate synergic substances and promote a controlled targeted drug delivery to the injured tissue. Therefore, our goal is to develop an Aristoflex® AVC hydrogel containing betamethasone dipropionate (BD) and borage oil (BO) nanocapsules and evaluate its stability in plastic and metal tubes during 120 days, at room temperature. Occlusive properties and permeation/penetration in vitro studies through skin were also performed. Nanocapsules were prepared by interfacial deposition of preformed polymer and incorporated into hydrogels (A-DBOBNC). Hydrogels without BD (A-OBNC) and with BD in solution (A-DB) were also prepared. Hydrogels containing nanocapsules showed bimodal granulometric distribution, nanometric size (193 to 203 nm), polidispersion index below 0.15, pH suitable for topical application (6.32 to 6.45) and drug concentration close to theoretical (0,25 mg/g). Spreadability factor (SF) was higher to A-OBNC (5.09 ± 0.23 mm²/g) than A-DBOBNC (2.93 ± 0.31 mm²/g) and A-DB (2.55 ± 0.11 mm²/g). All three formulations showed non-Newtonian behavior, which were better fitted to Power Law model (r>0,999; n<1), presenting pseudoplastic characteristics. Commercial cream (CC) presented micrometric size (2512 ± 291 nm), pH slightly acid (6.12 ± 0.28), SF of 4.46 ± 0.81 mm²/g and drug concentration around 90%. During 120 days hydrogel’s granulometric distribution, particle size and homogeneity were stable. At 90 days pH started to decrease for formulations packaged in aluminum tubes and at 30 days for plastic tubes. The SF changed for A-DBOBNC and A-OBNC and was stable for A-DB. The semissolids demonstrated higher occlusive factor at 12 hours of study, where AOBNC and A-DB were as occlusive as positive control (vaselin). Permeation/penetration in vitro skin studies evidenced high retention amount of BD at stratum cornea (A-DB: 12 g/cm²; A-DBOBNC: 7.7 g/cm²) confirming nanocapsules ability to control drug release. No distribution differences were observed in other skin layers between formulations. Additionally, gama-linoleic acid was found in skin dermis treated with A-OBNC, favorable result aiming skin barrier reconstruction. Therefore, the developed hydrogels can be considered technologically promising for topical application, aiming at the treatment of inflammatory skin diseases, such as atopic dermatitis.