Development of effervescent tablets containing benzonidazole complexed with cyclodextrin.

OBJECTIVES: Benznidazole (BNZ), the primary chemotherapy agent used to treat Chagas disease, has poor aqueous solubility, which results in low bioavailability. The purpose of this work was to develop stable effervescent tablets using an inclusion complex of BNZ with cyclodextrin (CD). METHOD: In the first phase, different CDs were evaluated according to their ability to improve the aqueous solubility of BNZ. Then, inclusion complexes of BNZ in the solid state were produced by the kneading method and the complexes were evaluated using several physical-chemical assays. Finally, effervescent tablets were prepared according to a complete 3(2) factorial design. The effects of the concentration of CD and effervescent mixture on the dissolution rate and physical stability of tablets were evaluated. KEY FINDINGS: Hydroxypropyl-ß-cyclodextrin produced the greatest improvement in the aqueous solubility of BNZ, almost 20-times greater than the water system. Solid systems produced with BNZ and CD showed physical-chemical interactions and increased the drug dissolution rate, suggesting the formation of a true solid inclusion complex. Moreover, the effervescent matrix of the tablets was effective in improving the dissolution behaviour of BNZ complexed with CD. CONCLUSIONS: Effervescent tablets produced using an inclusion complex of BNZ with CD suggest a possible improvement in the bioavailability of BNZ, and this could represent a relevant advance in Chagas therapy.

Benznidazole microcrystal preparation by solvent change precipitation and in vivo evaluation in the treatment of Chagas disease.

Benznidazole (BNZ) is traditionally used to treat Chagas disease. Despite its common use, BNZ has a poor water solubility and a variable bioavailability. The purpose of this study was to prepare BNZ microcrystals by solvent change precipitation and to study the effects of BNZ micronisation on therapeutic efficiency using a murine model of Chagas disease. The solvent change precipitation procedure was optimised in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. The thermal and crystallographic analysis showed no polymorphic change in the microcrystals, and microscopy confirmed a significant reduction in particle size. A marked improvement in the drug dissolution rate was observed for micronised BNZ particles and BNZ tablets in comparison with untreated BNZ and commercial Rochagan. In vivo studies showed a significant increase in the therapeutic efficacy of the BNZ microparticles, corroborating the dissolution results.

Avaliação do perfil lipídico, glicêmico, conteúdo de glicogênio hepático ecardíaco em ratos diabéticos suplementados com farinha de casca de maracujá (Passiflora edulis) / Assessment of the profile of lipids, glucose, liver and heart glucogen, in diabetic mice supplemented withpassion-fruit rind flour (Passiflora edulis) / Evaluación del perfil de lípidos, glucosa, contenido de glicógeno hepático y cardíaco, en ratones diabéticoscomplementados con harina de cáscara de maracuyá (Pasiflora edulis)

A ingestão de fibras alimentares está associada a redução do risco das complicações do diabetes mellitus, caracterizado pelos níveis elevados de glicose sangüínea. Com base nisto, o presente estudo propôs verificar o efeito da suplementação com farinha de casca de maracujá (Passiflora edulis) sobre os níveis plasmáticos de glicose, triglicérides, colesterol total e frações, e conteúdo de glicogênio hepático e cardíaco de ratos diabéticos. Utilizou-se 25 ratos, divididos em 5 grupos (n=5): grupo controle (GI) e grupo diabético (GII) que receberam ração comercial, dois grupos diabéticos tratados com ração suplementada com farinha de maracujá nas concentrações de 50 (GIII) e 100% (GIV) da dose correspondente à ingestão diária recomendada (IDR) de fibras, e grupo GV com ração suplementadacom 150% da IDR. Após o tratamento, coletou-se o plasma sangüíneo para análise dos parâmetros bioquímicos. No fígado e no coração, dosou-se o conteúdo de glicogênio. Em relação aos níveis lipídicos, não houve diferença significativa entre os grupos. A glicemia do GIII (137,60 ± 10,24 mg/dL)e GIV (153,60 ± 14,99 mg/dL) foi reduzida quando comparada ao GII (399,20 ± 37,21 mg/dL). O teor de glicogênio hepático e cardíaco, respectivamente, em GIII (22,91 ± 7,78 mg/g e 0,65 ± 0,09 mg/g)e GIV (28,29 ± 7,99 mg/g e 2,1 ± 0,19 mg/g) aumentou significativamente em relação ao GI (7,0 ± 4,71mg/g e 0,12 ± 0,01 mg/g), p<0,05. Conclui-se que a utilização da farinha de casca de maracujá nas concentrações de 50 e 100% da IDR foi efetiva para controle glicêmico e aumento do glicogênio hepático e cardíaco, não sendo efetiva na diminuição de lipídios plasmáticos no período de estudo.

The intake of alimentary fibers is associated to the reduction of the risk of complications with diabetes mellitus, which is characterized by high glucose levels in the blood. Based upon this,the present study aimed to check the effect of supplementation with passion fruit rind flour (Pasiflora edulis) on the glucose plasmatic levels, triglycerides, cholesterol total and fractions, and the hepatic and heart glucogen in diabetic mice. Twenty five mice were used, divided into 5 groups (n=5): control group (GI) and diabetic group (GII) which received commercial ration,two diabetic groups which received ration supplemented with passion fruit flour, 50% (GIII) and100% (GIV) concentrations of the recommended dose of daily fiber intake (RDI), and group(GV) having ration supplemented with 150% of the RDI. After the treatment, blood plasma was collected for the analysis of the biochemical parameters. The content of glucogen in the liver and the heart was quantified. In relation to the lipidic levels no significant difference was found among groups. The glucose level in GIII (137.60 + 10.24 mg/dL) and in GIV (153.60 + 14.99 mg/dL) was reduced when compared to GII (399.20 + 37.21 mg/dL). The level of hepatic and heart glucogen was significantly increased in GIII (22.91 + 7.71 mg/g and 0.65 + 0.09 mg/g) and GVI (28.29 + 7.99 mg/g) when compared to GI (7.0 + 4.71 mg/g and 0.12 + 0.01 mg/g), p<0.05. It was concluded that the use of flour from passion fruit rind in the concentrations of 50% and 100% was effective on the control of blood glucose and the increase of hepatic and heart glucogen, not being effective on the reduction of plasmatic lipids during the period of study.

La ingestión de fibras alimentares está asociada a la reducción del riesgo de complicaciones de la diabetes mellitus, caracterizada por elevados niveles de glucosa en la sangre. Con base en esto, el presente estudio se propuso verificar el efecto de la complementación con harina de cáscara de maracuyá (Pasiflora edulis) sobre los niveles plasmáticos de glucosa, triglicéridos, colesterol total y fracciones, y contenido de glicógeno hepático y cardíaco en ratones diabéticos. Se utilizaron 25 ratones, divididos en 5 grupos (n=5): grupo de controle (GI) y grupo diabético (GII) que recibieron ración comercial, dos grupos diabéticos tratados con ración complementada con harina de maracuyá, en las concentraciones de 50% (GIII) y 100% (IV) de la dosis correspondiente a la ingestión diaria recomendada (IDR) de fibras, y grupo (GV) con ración complementada con 150% de la IDR. Tras el tratamiento se colectó el plasma de la sangre para el análisis de los parámetros bioquímicos. En el hígado y en el corazón se ha dosificado el contenido de glicógeno. Con relación a los niveles lípidos no hubo diferencia significativa entre los grupos. La glicemia del GIII (137,60 + 10,24 mg/dL) y GIV (153,60 + 14,99 mg/dL)se ha reducido cuando comparada con GII (399,20 + 37,21 mg/dL). El contenido de glicógenohepático y cardíaco, respectivamente, en GIII (22,91 + 7,78 mg/g y 0,65 + 0,09 mg/g) y GIV(28,29 + 7,99 mg/g y 2,1 + 0,19 mg/g) ha aumentado significativamente con relación al GI (7,0+ 4,71 mg/g), p<0,05. Se ha concluido que la utilización de la harina de cáscara de maracuyá,en las concentraciones de 50% y 100% de la IDR, fue efectiva para el control de la glucosa y del aumento del glicógeno hepático y cardíaco, no resultando efectivo en la reducción de lípidos plasmáticos durante el periodo del estudio.