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

被引：34

作者：

Maximiano, Flavia Pires ^{[2
]}

de Paula, Livia Maria ^{[2
]}

Figueiredo, Vivian Paulino ^{[3
]}

de Andrade, Isabel Mayer ^{[3
]}

Talvani, Andre ^{[3
]}

Sa-Barreto, Livia C.

Bahia, Maria Terezinha ^{[3
]}

Cunha-Filho, Marcilio S. S. ^{[1
]}

机构：

[1] Univ Fed Mato Grosso UFMT, Inst Ciencias Saude, Setor Ind, BR-78557267 Sinop, MT, Brazil

[2] Univ Fed Ouro Preto, Escola Farm, Ouro Preto, MG, Brazil

[3] Univ Fed Ouro Preto, Inst Ciencias Exatas & Biol, Ouro Preto, MG, Brazil

来源：

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2011年 / 78卷 / 03期

关键词：

Benznidazole; Chagas disease; Solvent change precipitation; Dissolution rate; Microcrystals; DISSOLUTION RATE ENHANCEMENT; SITU-MICRONIZATION; DRUG-DELIVERY; FORMULATIONS;

D O I：

10.1016/j.ejpb.2011.03.003

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 (R), In vivo studies showed a significant increase in the therapeutic efficacy of the BNZ microparticles, corroborating the dissolution results. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：377 / 384

页数：8

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