Dispers?es s?lidas de sinvastatina: prepara??o, caracteriza??o, no estado s?lido utilizando t?cnicas emergentes e estudo de estabilidade

Autor: Vargas, Mara R?bia Winter de
Jazyk: portugalština
Rok vydání: 2014
Předmět:
Zdroj: Repositório Institucional da UFRNUniversidade Federal do Rio Grande do NorteUFRN.
Druh dokumentu: Doctoral Thesis
Popis: Made available in DSpace on 2014-12-17T14:25:23Z (GMT). No. of bitstreams: 1 MaraRWV_TESE.pdf: 3541177 bytes, checksum: 2415c9163a59f9b397912f22608eefbc (MD5) Previous issue date: 2014-05-29
Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
This thesis aimed to assess the increase in solubility of simvastatin (SINV) with solid dispersions using techniques such as kneading (MA), co-solvent evaporation (ES), melting carrier (FC) and spray dryer (SD). Soluplus (SOL), PEG 6000 (PEG), PVP K-30 (PVP) e sodium lauryl sulphate (LSS) were used as carriers. The solid dispersions containing PEG [PEG-2(SD)], Soluplus [SOL-2(MA)] and sodium lauryl sulphate [LSS-2(ES)] were presented with a greater increase in solubility (5.02, 5.60 and 5.43 times respectively); analyses by ANOVA between the three groups did not present significant difference (pPEG >PVP 75%>LSS, always 80%. The phase diagrams of PEG and LSS presented solubilization stoichiometry of type 1:1 (type AL). The diagrams with PVP and SOL tend to 1:2 stoichiometry (type AL + AP). The stability coefficients (Ks) of the phase diagrams revealed that the most stable reactions occurred with LSS and PVP. The solid dispersions were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), particle size distribution (PSD), near-infrared spectroscopy imaging (NIR-CI) and X-ray diffraction of the powder using the Topas software (PDRX-TOPAS). The solid dispersion PEG-2(SD) presented the greatest homogeneity and the lowest degree of crystallinity (18.2%). The accelerated stability study revealed that the solid dispersions are less stable than SINV, with PEG-2(SD) being the least stable, confirmed by FTIR and DSC. The analyses by PDRX-TOPAS revealed the amorphous character of the dispersions and the mechanism of increasing solubility
Esta tese teve como objetivo avaliar o aumento de solubilidade da sinvastatina (SINV) atrav?s de dispers?es s?lidas utilizando as t?cnicas de malaxagem (MA), evapora??o com co- solvente (ES), fus?o com carreador (FC) e secagem por spray dryer (SD). Foram utilizados os carreadores Soluplus (SOL), PEG 6000 (PEG), PVP K-30 (PVP) e lauril sulfato de s?dio (LSS). As dispers?es s?lidas contendo PEG [PEG-2(SD)], Soluplus [SOL-2(MA)] e lauril sulfato de s?dio [LSS-2(ES)] apresentaram maior aumento de solubilidade (5,02; 5,60 e 5,43 vezes, respectivamente); a an?lise por ANOVA entre os tr?s grupos n?o demonstrou diferen?a significativa (pPEG >PVP 75%>LSS, sempre a 80%. Os diagramas de fases de PEG e LSS apresentaram estequiometria de solubiliza??o 1:1 (tipo AL). Os diagramas de PVP e SOL possuem uma tend?ncia a estequiometria 1:2 (tipo AL + AP). Os valores de coeficiente de estabilidade (Ks) dos diagramas de fases revelaram que as rea??es mais est?veis ocorreram com LSS e PVP. As dispers?es s?lidas foram caracterizadas atrav?s de infravermelho com transformada de Fourier (FTIR), calorimetria explorat?ria diferencial (DSC), microscopia eletr?nica de varredura (MEV), distribui??o de tamanho de part?cula (DTP), espectroscopia de imagem no infravermelho pr?ximo (NIR-CI) e difratometria de raios X do P? utilizando o software Topas (PDRX-TOPAS). A dispers?o s?lida PEG-2(SD) apresentou a maior homogeneidade e o menor grau de cristalinidade (18,2%). O estudo de estabilidade revelou que as dispers?es s?lidas s?o menos est?veis que SINV, sendo PEG-2(SD) a de menor estabilidade, confirmada por FTIR e DSC. As an?lises por PDRX-TOPAS revelaram a cristalinidade das dispers?es e o mecanismo de aumento de solubilidade
Databáze: Networked Digital Library of Theses & Dissertations
Externí odkaz: