Desenvolvimento de dispersões sólidas para liberação colônica de metronidazol
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Data
2008-01-23
Autores
Ferrari, Priscileila Colerato [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Os sistemas de liberação colônica de fármacos têm sido amplamente estudados, a fim de se obter medicamentos que possam atuar de maneira mais específica no colón para o tratamento de doenças que acometem essa região do intestino. Com essa finalidade, em trabalhos anteriores do nosso grupo de pesquisa foram preparados sistemas multiparticulados constituídos de quitosana, pectina e alginato. Estudos subseqüentes incluíram polímeros gastrorresistentes, como acetoftalato de celulose e ftalato de hidroxipropilmetilcelulose, a fim de se evitar uma liberação gástrica prematura do fármaco a partir desses sistemas. No presente trabalho foram preparadas dispersões sólidas de metronidazol, constituídas de quitosana e polímeros gastrorresistentes. A utilização da quitosana se deve à presença de enzimas colônicas que a degradam, e os polímeros derivados de celulose são utilizados devido à sua insolubilidade nos meios com baixos valores de pH. Esses sistemas foram preparados por evaporação do solvente, analisados por espectrofotometria no UV e IV, caracterizados morfologicamente e granulometricamente com a utilização de estereoscópio, sendo que mais de 50% das partículas apresentaram-se na faixa de distribuição de tamanho entre 0,003 e 0,06 mm, indicando que a dissolução poderá ser facilitada devido ao aumento considerável da área superficial disponível. Também foram analisados quanto à capacidade de intumescimento, demonstrando que a presença de CAP e QS interfere nas propriedades de intumescimento das dispersões sólidas. As dispersões sólidas foram analisadas in vitro quanto à sua capacidade de atingir a região colônica. Primeiramente, foi observado que durante 2h de experimento 60% de fármaco livre foram dissolvidos em meio gástrico simulado. Isso se deve à baixa solubilidade do metronidazol e à necessidade de um tempo maior de ensaio...
Colonic drug delivery systems have been widely studied, purposing to obtain dosage forms able to act more specifically at the colon in order to treat typical diseases of this intestinal region. According to this goal, in previous works of our research group, multiparticulate systems constituted by chitosan, pectin and alginate were prepared and characterized. Subsequent studies included enteric polymers, such as cellulose acetate phtalate (CAP) and hydroxypropylmethylcellulose phtalate (HPMCP), aiming to avoid the premature gastric release of the drug from these systems. In the present work, solid dispersions containing metronidazol (MT) and based on chitosan (CS) and the referred enteric polymers were prepared. The use of CS is due to the presence of colonic enzymes that specifically degrade it and the enteric polymers were used due to their insolubility in environments with low pH values. These systems were prepared by solvent evaporation, analyzed by UV and IR spectrophotometries and morphologically and granulometrically characterized by means of a stereoscope. By this latest assay, more than 50% of the particles showed a size distribution range from 0.003 to 0.06 mm, indicating that a further dissolution can be facilitated due to the considerable increasing of the superficial area available to solvation. The systems were also characterized in respect to the swelling capacity, demonstrating that the presence of CAP and CS influence the swelling properties of the solid dispersions. The ability of the solid dispersions to reach the colonic region was also assessed in vitro. At first, it was observed that 60% of the drug was released into simulated gastric fluid during the first 2h of assay. This is explained by the low solubility of MT. From the solid dispersions, during the same time period, 25% to 45% of the drug was released into this medium. These results indicate the effective gastric... (Complete abstract click electronic access below)
Colonic drug delivery systems have been widely studied, purposing to obtain dosage forms able to act more specifically at the colon in order to treat typical diseases of this intestinal region. According to this goal, in previous works of our research group, multiparticulate systems constituted by chitosan, pectin and alginate were prepared and characterized. Subsequent studies included enteric polymers, such as cellulose acetate phtalate (CAP) and hydroxypropylmethylcellulose phtalate (HPMCP), aiming to avoid the premature gastric release of the drug from these systems. In the present work, solid dispersions containing metronidazol (MT) and based on chitosan (CS) and the referred enteric polymers were prepared. The use of CS is due to the presence of colonic enzymes that specifically degrade it and the enteric polymers were used due to their insolubility in environments with low pH values. These systems were prepared by solvent evaporation, analyzed by UV and IR spectrophotometries and morphologically and granulometrically characterized by means of a stereoscope. By this latest assay, more than 50% of the particles showed a size distribution range from 0.003 to 0.06 mm, indicating that a further dissolution can be facilitated due to the considerable increasing of the superficial area available to solvation. The systems were also characterized in respect to the swelling capacity, demonstrating that the presence of CAP and CS influence the swelling properties of the solid dispersions. The ability of the solid dispersions to reach the colonic region was also assessed in vitro. At first, it was observed that 60% of the drug was released into simulated gastric fluid during the first 2h of assay. This is explained by the low solubility of MT. From the solid dispersions, during the same time period, 25% to 45% of the drug was released into this medium. These results indicate the effective gastric... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Dispersões sólidas, Metronidazol, Liberação colônica de fármacos
Como citar
FERRARI, Priscileila Colerato. Desenvolvimento de dispersões sólidas para liberação colônica de metronidazol. 2008. 96 f. Dissertação (mestrado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2008.