Enhancement of dissolution rate through eutectic mixture and solid solution of posaconazole and benznidazole

Publication date: 15 June 2017 Source:International Journal of Pharmaceutics, Volume 525, Issue 1 Author(s): Camila Bezerra Melo Figueirêdo, Daniela Nadvorny, Amanda Carla Quintas de Medeiros Vieira, José Lamartine Soares Sobrinho, Pedro José Rolim Neto, Ping I. Lee, Monica Felts de La Roca Soares Benznidazole (BNZ), the only commercialized antichagasic drug, and the antifungal compound posaconazole (PCZ) have shown synergistic action in the therapy of Chagas disease, however both active pharmaceutical ingredients (APIs) exhibit low aqueous solubility potentially limiting their bioavailability and therapeutic efficacy. In this paper, we report for the first time the formation of a eutectic mixture as well as an amorphous solid solution of PCZ and BNZ (at the same characteristic ratio of 80:20wt%), which provided enhanced solubility and dissolution rate for both APIs. This eutectic system was characterized by DSC and the melting points obtained were used for the construction of a phase diagram. The preservation of the characteristic PXRD patterns and the IR spectra of the parent APIs, and the visualization of a characteristic eutectic lamellar crystalline microstructure using Confocal Raman Microscopy confirm this system as a true eutectic mixture. The PXRD result also confirms the amorphous nature of the prepared solid solution. Theoretical chemical analyses indicate the predominance of π-stacking interactions in the amorphous solid solution, whereas an electrost...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research