A Preformulation Study of a New Medicine for Chagas Disease Treatment: Physicochemical Characterization, Thermal Stability, and Compatibility of Benznidazole

作者：Soares Sobrinho Jose Lamartine^*; de La Roca Soares Monica Felts; Lopes Pablo Queiroz; Correia Lidiane Pinto; de Souza Fabio Santos; Macedo Rui Oliveira; Rolim Neto Pedro Jose

来源：AAPS PharmSciTech, 2010, 11(3): 1391-1396.

DOI：10.1208/s12249-010-9495-8

• binary mixtures
• Chagas disease
• drug stability
• excipients
• preformulation

This work aimed the studies of physicochemical characterization, thermal stability, and compatibility of benznidazole (BNZ) drug by spectroscopy (NMR, IR), thermoanalytical (differential thermal analysis, differential scanning calorimetry, and thermogravimetry), and chromatographic (HPLC) techniques, beyond the analytical tools of Van't Hoff equation and Ozawa model. The compatibility study was conducted by binary mixtures (1:1, w/w) of the drug with microcrystalline cellulose 102 and 250, anhydrous lactose, and sodium starch glycolate. The physicochemical characterization confirmed data reported in scientific literature, guaranteeing authenticity of the analyzed raw material. The drug melts at 191.68 degrees C (Delta H, 119.71 J g(-1)), characteristic of a non-polymorphic raw material, and a main stage decomposition at 233.76-319.35 degrees C (Delta m, 43.32%) occurred, ending the study with almost all mass volatilized. The quantification of drug purity demonstrated a correlation of 99.63% between the data obtained by chromatographic (99.20%) and thermoanalytical technique (99.56%). The Arrhenius equation and Ozawa model showed a zero-order kinetic behavior for the drug decomposition, and a calculated provisional validity time was 2.37 years at 25 degrees C. The compatibility study evidenced two possible chemical incompatibilities between BNZ and the tested excipients, both associated by the authors to the reaction of the BNZ's amine and a polymer carbohydrate's carbonile, being maillard reactions. The BNZ reaction with anhydrous lactose is more pronounced than with the sodium starch glycolate because the lactose has more free hydroxyl groups to undergo reduction by the drug. In this sense, this work guides the development of a new solid pharmaceutical product for Chagas disease treatment, with defined quality control parameters and physicochemical stability.

• 出版日期2010-9