Preformulation studies of itraconazole associated with benznidazole and pharmaceutical excipients

Recent studies have shown that the antifungal itraconazole (ITZ), when in associations with benznidazole (BNZ), is a potential treatment for Chagas disease. Therefore, the objective of the present study was to evaluate the compatibility of ITZ with BNZ and with selected pharmaceutical excipients. Differential scanning calorimetry (DSC), derivative thermogravimetry (DTG), Fourier transform infrared spectroscopy (FTIR), optical microscopy and kinetic analyses under isothermal conditions were performed. The results showed thermal interactions between ITZ and the excipients hydroxypropyl methylcellulose and polyvinylpyrrolidone. The FTIR data together with complementary tests revealed signs of drug decomposition in the presence of these materials. Thus, these excipients were considered incompatible with ITZ and should be avoided in solid dosage forms containing this drug. Moreover, it was found that associations between ITZ and BNZ are potentially unstable. Therefore, it is necessary to develop a pharmaceutical dosage form that avoids the processing of these drugs together and allows a stable pharmaceutical formulation to be obtained. (C) 2013 Elsevier B.V. All rights reserved.