Caracterização de implantes poliméricos biodegradáveis contendo sirolimus e avaliação de sua estabilidade em condições de estresse químico

• Ano de defesa: 2016
• Autor(a) principal: Campos, Michele Soares Tacchi
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Mestrado em Ciências Farmacêuticas; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Ciências Farmacêuticas
• Palavras-chave em Português: Thermal analysis; X-ray analysis; Biodegradable implants; Polymers; Kinects; Implantes absorvíveis; Cinética; Sirolimus; Análise térmica; Sirolimo; Implantes biodegradáveis; Polímeros; Implantes artificiais; Dinâmica; Raios X - Difração; Farmácia; 615.1
• Link de acesso: http://repositorio.ufes.br/handle/10/5307

The use of sirolimus and its analogs has been evaluated in studies aimed at combating several types of cancer; however, because of the limited bioavailability of the drug, the search for new forms of administration is required. Biodegradable polymeric implants containing sirolimus were assessed as an alternative method of drug administration. Distinct implants containing 25% (w/w) sirolimus were prepared employing the polymer matrices chitosan, polycaprolactone and Poly(lactic-co-glycolic acid) (PLGA) in two proportions: PLGA 50:50 and PLGA 75:25. Thermal analysis techniques such as thermogravimetry and differential scanning calorimetry, combined with x-ray diffraction and microscopy were used to characterize and evaluate the compatibility of the constituents of the formulation, no incompatibilities were found between the components, but drug amorphization was observed in all samples. Sirolimus was unstable when exposed to conditions: heat, neutral and basic hydrolysis, at the analysis by high-performance liquid chromatography (HPLC ) were detected two degradation products after exposure to heat and detected one degradation product after basic hydrolysis and neutral hydrolysis, the degradations product showed similar UV spectrum to the drug’s spectrum. Through the isothermal kinetic study on solid media, it was observed that the drug molecule degrades second diffusive three-dimensional model, with validity time to 6 years. HPLC analysis showed that the lyophilized powder for elaboration of the implant prepared with PLGA 75:25 did not present degradation products and maintained its appropriate drug content of 24,6%, after analysis in solution by HPLC, and represents the most suitable polymer for use in developed by biodegradable implants containing Sirolimus for the treatment of malignant solid tumors, however, is still necessary to further study the drug effects after amorphization of the crystal and also stability and solubility analysis