Submitted by RANIELLE DE OLIVEIRA SILVA null (ranielleborges@yahoo.com.br) on 2016-06-14T16:20:17Z No. of bitstreams: 1 DissertaçãoMestrado_Ranielle_Silva 2.pdf: 11995453 bytes, checksum: abf2ac6021bf67009b8af99fe28a0026 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-06-16T14:40:09Z (GMT) No. of bitstreams: 1 silva_ro_me_araiq_par.pdf: 1314893 bytes, checksum: 9254863d01a93bf48fa2f06ae37a9209 (MD5) / Made available in DSpace on 2016-06-16T14:40:09Z (GMT). No. of bitstreams: 1 silva_ro_me_araiq_par.pdf: 1314893 bytes, checksum: 9254863d01a93bf48fa2f06ae37a9209 (MD5) Previous issue date: 2016-05-09 / Híbridos Siloxano-PPO obtidos pela síntese sol-gel foram utilizados como matrizes carreadoras do fármaco cloridrato de propranolol com interesse de se aumentar a disponibilidade do fármaco em meio aquoso. Foram preparados amostras contendo teores de 5 e 30% do fármaco. A eficiência na formação da rede híbrida foi confirmada por análises FTIR, RMN e SAXS. A cinética de liberação mostrou que ela ocorre de forma prolongada (superior a 1200 h) com regimes intermitentes de aceleração e desaceleração da taxa de liberação. Foram aplicados ajustes matemáticos a cada regime utilizando a equação de Korsmayer-Peppas que demonstraram que a saída do fármaco ocorre por diferentes mecanismos. Observou-se que o acesso da água na amostra durante a liberação não é homogêneo, mas sim gradual da superfície ao centro. Devido a esses fenômenos as caracterizações foram feitas em diferentes regiões da amostra (periferia e centro) e em diferentes períodos da liberação, visando acompanhar a difusão da água para o interior da amostra e a cinética de saída do fármaco. As análises estruturais de DRX e as térmicas por TGA e DSC mostraram que o fármaco é incorporado na matriz híbrida na forma solubilizada e na forma cristalina. As medias realizadas em função do tempo mostraram que a velocidade de saída do fármaco e de entrada da água na matriz híbrida é maior na superfície em relação ao volume, confirmando o acesso gradual da água. Essas análises indicam a correlação entre as fases cristalina do fármaco com os primeiros regimes e da parte solubilizada com a liberação mais lenta. As medidas de DSC mostraram que o acesso da água em regiões mais internas da amostra resultaram no comportamento de confinamento da água, indicado pelo fenômeno de super congelamento. Foi detectado por medias de SAXS a existência de espalhadores secundários presentes em todas as amostras, inclusive nas matrizes híbridas sem a adição de fármaco, que foram atribuídos a agregados formados por domínios com maior densidade de nanopartículas de sílica. A evolução no tamanho desses agregados foi correlacionada aos regimes de liberação. Conclui-se, que a cinética de liberação tem uma forte dependência da evolução da matriz híbrida causadas por mudanças estruturais favorecidas pela mobilidade da cadeia polimérica e pela interação do fármaco com a água. / Siloxane-PPO hybrids obtained by sol-gel synthesis have been used as drug delivery systems for propranolol hydrochloride with the intent to increase the drug availability in the aqueous medium. Samples with 5% and 30% of drug have been prepared. The efficiency related to the formation of the hybrid network has been confirmed by means of FTIR, RMN and SAXS analyses. The drug delivery kinetics showed that it occurs in a prolonged form (more that 1200h) with increasing and decreasing intermediate release rates. The Korsmayer-Peppas equation has been used for each release rate with mathematical adjustments that displayed how the drug release occurred through different mechanisms. It has been observed that the water intake inside the sample during the drug release was not homogeneous but gradual, from the surface to the centre. Due to these phenomena, the characterizations have been carried out in different regions of the samples (exterior and interior) and at different drug delivery periods, aiming at accompanying the water diffusion to the sample centre and the drug release kinetics. The XRD structural analyses and the thermal analyses by means of TGA and DSC showed that the drug is incorporated in the hybrid matrix in a solubilized form and in a crystalline form. The tests done as function of time displayed that the drug release velocity and water intake inside the hybrid matrix is greater at the surface in relation to its volume, confirming the gradual access of water. These analyses point to the correlation between the drug crystalline phase with the first release regimes and between the solubilized form with the slower release. The DSC tests showed that the water intake inside more internal regions of the sample resulted in the water confinement, demonstrated by the super-cooling phenomenon. By means of SAXS, the existence in all the samples, including those without drug, of secondary scatterings has been observed and these have been attributed to aggregates formed by domains with a higher silica nanoparticle density. The size evolution of these aggregates has been correlated to the drug release regimes. It has been concluded that the drug release kinetics has a strong dependence with the hybrid matrix evolution caused by structural changes facilitated by polymer chain mobility and by drug/water interaction.

The adsorption isotherm of two weak bases, Promethazine hydrochloride and Propranolol hydrochloride, were determined with isocratic reversed-phase liquid chromatography, with a 60 w% methanol in 20 mM sodium acetate buffer pH 4 as the mobile phase, and calculated by the elution by characteristic points method. The data obtained from the method were then fitted into the Langmuir isotherm and the electrostatically modified Langmuir. Propranolol fitted reasonably good into the models while Promethazine was not as good. When Promethazine and Propranolol were together in the same sample, there was indication of competition of the adsorption sites. For comparing retention and peak shape between a C18 column and a mixed mode column, Waters XBridge C18 and Thermo Scientific Acclaim WCX-1, were tested in gradient elution with 11.32 mM sodium acetate buffer and 10–70 % methanol. The mixed-mode column gave significantly better peak shapes, while the retention time were longer compared to the C18 column. / Adsorptions-isotermerna för två svaga baser, Prometazin hydroklorid och Propranolol hydroklorid, bestämdes med isokratisk omvänd-fas vätskekromatografi, med w% 60 metanol i en 20 mM natriumacetatbuffert pH 4 som mobil fas, och beräknad med metoden elution by characteristic points.  Från metoden erhållna data passades till Langmuir isotherm och den elektrostatiskt modifierade Langmuir. Propanolen passade ganska bra till de olika isotermerna, medan Prometazin var något sämre passad. När Prometazin och Propranolol var tillsammans i samma prov, fanns det indikationer på konkurrens om adsorptionsställen. För jämförelse av topparnas form och retentionstid mellan en C18-kolonn och en mixed-mode-kolonn, användes Waters XBridge C18 och Thermo Scientific Acclaim WCX-1, som testades i gradient eluering med 11, 32 mM natriumacetatbuffert och 10–70 % metanol. Mixed-mode-kolonnen gav åtskilligt bättre toppar, medan retentionstiden var längre jämfört med C18-kolonnen.