Enhanced delivery of fixed-dose combination of synergistic antichagasic agents posaconazole-benznidazole based on amorphous solid dispersions.

Posaconazole (PCZ) and benznidazole (BNZ) are known to show synergetic effect in treating the acute and chronic phases of Chagas disease, a neglected parasitic disease. However, as both compounds are poorly water soluble, the development of amorphous solid dispersions (ASDs) of a PCZ/BNZ fixed-dose combination in a water-soluble polymer becomes an attractive option to increase their apparent solubility and dissolution rate, potentially improving their oral bioavailability. The initial approach was to explore solvent evaporated solid dispertion (SD) systems for a PCZ/BNZ 50:50 (wt%) combination at several total drug loading levels (from SD with 10% to 50% drug loading) in water-soluble carriers, including polyvinylpyrrolidone (PVP K-30) and vinylpyrrolidone-vinyl acetate copolymer (PVPVA 64).

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

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.

Solid dispersion of efavirenz in PVP K-30 by conventional solvent and kneading methods.

Efavirenz (EFV) used as a part of the treatment of first choice in antiretroviral therapy for AIDS has low aqueous solubility and presents problems of absorption. We thus initially present a phase solubility diagram with carriers of different classes. With a view to obtaining a solid dispersion (SD) with suitable consistency to that of a solid formulation, we chose to use PVP K-30, since polymers present some of the best results.