Soluções sólidas vs. dispersões sólidas: impacto dos parâmetros de formulação
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Data
2014
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Edições Universitárias Lusófonas
Resumo
Filmes matriciais foram preparados com fármacos com diferentes solubilidades aquosas (tartarato de metoprolol, ibuprofeno e diclofenac Na) e diferentes polímeros (etilcelulose, Eudragit RS e Eudragit RL). Foram obtidas soluções sólidas (fármaco dissolvido) e dispersões sólidas (fármaco disperso). A libertação dos fármacos foi estudada em função do tipo de fármaco, doseamento, tipo e quantidade de aditivo e do tipo de polímero. A libertação dos fármacos não foi de acordo com a sua solubilidade aquosa, mas sim com o estado físico do fármaco na matriz. O incremento do conteúdo do fármaco na matriz aumentou a velocidade de libertação monotonicamente para a solução sólida. Em contraste, com a dispersão sólida, o aumento da dosagem de fármaco não originou quase nenhum efeito até 30 %, registando-se apenas, posteriormente, um acréscimo na sua velocidade. A inclusão de aditivos hidrofílicos aumentou principalmente a fase inicial do perfil de libertação do fármaco e não produziu efeito no plateau. Por outro lado, polietilenoglicol 1500 diminuiu a libertação de diclofenac Na devido ao aprisionamento do fármaco nos seus domínios. O efeito do tipo de polímero na libertação de ibuprofeno esteve relacionado com a partição do fármaco com o polímero. No caso do tartarato de metoprolol, a libertação foi muito mais rápida do da matriz de Eudragit RS do que de EC, devido à formação de uma mistura amorfa.
Matrix films were prepared with drugs with different aqueous solubility (metoprolol tartrate, ibuprofen and diclofenac Na) and different polymers (ethylcellulose, Eudragit RS and Eudragit RL). Solid solutions (drug dissolved) and solid dispersions (drug dispersed) were obtained. The drug release was studied as a function of drug type and loading, additive type and amount and polymer type. Drug release from the matrices was not in accordance with drug aqueous solubility, but rather with the physical state of the drug in the matrix. Increasing the drug loading increased the drug release rate in a monotonical fashion for the solid solution. In contrast, increasing the drug loading with the solid dispersion had almost no effect until 30 %. An increase in speed was only registered after the drug release significantly increased. The addition of hydrophilic additives mainly increased the initial phase of the release profile, with no effect on the plateau. On the contrary, polyethylene glycol 1500 was shown to decrease the release of diclofenac Na due to entrapment of the drug in the hydrophilic additive domains. The effect of polymer type on ibuprofen release correlated well with the partition of the drug into the polymer. In the case of metoprolol tartrate, drug release was much faster from Eudragit RS than EC matrices due to the formation of an amorphous mixture with Eudragit RS polymer.
Matrix films were prepared with drugs with different aqueous solubility (metoprolol tartrate, ibuprofen and diclofenac Na) and different polymers (ethylcellulose, Eudragit RS and Eudragit RL). Solid solutions (drug dissolved) and solid dispersions (drug dispersed) were obtained. The drug release was studied as a function of drug type and loading, additive type and amount and polymer type. Drug release from the matrices was not in accordance with drug aqueous solubility, but rather with the physical state of the drug in the matrix. Increasing the drug loading increased the drug release rate in a monotonical fashion for the solid solution. In contrast, increasing the drug loading with the solid dispersion had almost no effect until 30 %. An increase in speed was only registered after the drug release significantly increased. The addition of hydrophilic additives mainly increased the initial phase of the release profile, with no effect on the plateau. On the contrary, polyethylene glycol 1500 was shown to decrease the release of diclofenac Na due to entrapment of the drug in the hydrophilic additive domains. The effect of polymer type on ibuprofen release correlated well with the partition of the drug into the polymer. In the case of metoprolol tartrate, drug release was much faster from Eudragit RS than EC matrices due to the formation of an amorphous mixture with Eudragit RS polymer.
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CIÊNCIAS FARMACÊUTICAS, SISTEMAS DE LIBERTAÇÃO DE MEDICAMENTOS, FARMACOLOGIA, MEDICAMENTOS, PHARMACEUTICAL SCIENCES, DRUG DELIVERY SYSTEMS, PHARMACOLOGY, DRUGS
Citação
Mota , J 2014 , ' Soluções sólidas vs. dispersões sólidas: impacto dos parâmetros de formulação ' , Biomedical and biopharmaceutical research : jornal de investigação biomédica e biofarmacêutica , vol. 10 , no. 2 , pp. 235-248 . https://doi.org/10.19277/BBR.10.2.68