Micofenolato de mofetila (MMF) e micofenolato sódico (MPS) são, respectivamente, éster e sal sódico do ácido micofenólico. Os fármacos possuem características farmacocinéticas distintas em função das diferenças na estrutura molecular, nas propriedades físico-químicas e nas formulações administradas. Neste trabalho, os perfis de dissolução dos medicamentos referências foram testados em diferentes meios de dissolução com o objetivo de avaliar o efeito da variação de pH, a cinética de dissolução e o modelo estatístico mais adequado para prever a dissolução dos fármacos. A liberação dos fármacos foi determinada com método validado por espectroscopia no ultravioleta, λ 250 nm. O método mostrou-se seletivo, linear, preciso e exato para dissolução de MMF em 0,1 M HCl e MPS em tampão fosfato pH 6,8. Os modelos cinéticos de dissolução de ordem zero, primeira ordem, Higuchi, Hixson-Crowell e Weibull foram aplicados com o objetivo de selecionar aquele com o melhor ajuste por regressão linear. Os parâmetros de regressão foram estimados e os ajustes dos modelos foram verificados pelos resíduos e coeficientes de determinação. Os resíduos obtidos foram aleatórios, independentes, apresentaram variância constante e seguiram a distribuição normal. Os valores de R² (74,7% para MMF e 95,8% para MPS) indicaram bom ajuste da regressão de Weibull para explicar a variabilidade e estimar a liberação dos fármacos.

Mycophenolate mofetil (MMF) and mycophenolate sodium (MPS) are an ester and a salt of mycophenolic acid. They have different kinetic in vivo characteristics due to differences in molecular structures, physicochemical properties and formulations administered. In this study, dissolution profiles of reference products were tested in different media to evaluate the effect of pH, kinetic dissolution and the best statistical model that can be used to predict the release of both drugs. The drug release was determined by using a validated ultraviolet spectrophotometry method, λ 250 nm. The method showed to be selective, linear, precise and accurate for MMF in 0.1 M HCl and MPS in sodium phosphate buffer pH 6.8. Dissolution kinetics models of zero order, first order, Higuchi, Hixson-Crowell and Weibull were applied to data in order to select the best fit by linear regression. The regression parameters were estimated and the models were evaluated with the results of residuals and coefficient of determination. The residuals obtained from dissolution kinetics models were random, uncorrelated, and normally distributed with constant variance. The R² values (74.7% for MMF and 95.8% for MPS) demonstrated good ability of the Weibull regression to explain the variability and to predict the drugs' release.

OBJECTIVE: To estimate diabetes-related deaths among Brazilian adults between 1999 and 2003 and to investigate demographic factors associated with reporting diabetes as an associated cause of death. METHODS: All deaths with diabetes as the underlying or associated cause were identified using the Brazilian Mortality Data System. Analysis was performed by sex, age, year, state of residence, and place of death. Mortality rates were age standardized by the 2000 Brazilian population. FINDINGS: A total of 237 946 deaths (8.8%) were related to diabetes; in 4.2% of deaths it was the underlying cause and in 4.6% it was an associated cause. Between 1999 and 2003, age-standardized mortality rates for diabetes as the underlying cause increased 14% among males and 9% among females, while mortality with diabetes as an associated cause increased 22% and 28%, respectively. Diabetes appeared more often as an associated cause in death certificates among older individuals and in those residing in São Paulo State; it appeared less often as an associated cause among women, brown- and black-skinned populations, and in deaths occurring outside hospitals. Cardiovascular diseases accounted for 54.5% of the underlying causes of death when diabetes was an associated cause. CONCLUSION: Diabetes was related to almost 9% of the deaths in the South and Southeast regions of Brazil. Mortality from diabetes is increasing, especially deaths with diabetes as an associated cause. The probability of having diabetes as the underlying cause of death is greater among women and nonwhite individuals. Our results reinforce the importance of using multiple causes of death to monitor diabetes, because half the individuals with the disease will die of another cause, especially cardiovascular diseases.

OBJETIVOS: Estimar las muertes relacionadas con la diabetes en adultos brasileños entre 1999 y 2003 y analizar los factores demográficos asociados con el informe de la diabetes como causa asociada de muerte. MÉTODOS: Se identificaron todas las muertes en que la diabetes fue la causa principal o asociada, a partir del Sistema Brasileño de Datos de Mortalidad. El análisis se realizó según el sexo, la edad, el año, el estado de residencia y el lugar de muerte. Las tasas de mortalidad se estandarizaron por la edad según la población brasileña en 2000. RESULTADOS: En total, 237 946 muertes (8,8%) estuvieron relacionadas con la diabetes; en 4,2% de las muertes, la diabetes fue la causa principal y en 4,6% fue una causa asociada. Entre 1999 y 2003, las tasas de mortalidad estandarizadas según la edad para las muertes en que la diabetes fue la causa principal aumentaron 14% en hombres y 9% en mujeres, mientras que la mortalidad con la diabetes como causa asociada aumentó a 22% y 28%, respectivamente. La diabetes apareció más frecuentemente como causa asociada en los certificados de defunción de la personas de mayor edad y en los que residían en el Estado de São Paulo, mientras que fue menos frecuente en mujeres, negros y mestizos y cuando la muerte ocurrió fuera de los hospitales. Las enfermedades cardiovasculares fueron la causa principal de 54,5% de las muertes en las que la diabetes se consideró como causa asociada. CONCLUSIONES: La diabetes estuvo relacionada con casi 9% de las muertes ocurridas en las regiones sur y suroriental de Brasil. La mortalidad por diabetes está en aumento, especialmente cuando la diabetes figura como causa asociada de muerte. La probabilidad de tener diabetes como causa principal de muerte es mayor en mujeres y en personas que no son blancas. Estos resultados confirman la importancia de utilizar la información de las múltiples causas de muerte para analizar la diabetes, ya que la mitad de las personas con esta enfermedad morirá por otra causa, especialmente por enfermedades cardiovasculares.