title: Development of novel benznidazole formulations: physicochemical characterization and in vivo evaluation on parasitemia reduction in Chagas disease.
abstract: This work aims to develop novel benznidazole (BZN) solid dispersions (SD) to improve its solubility and bioavailability properties. Low-substituted hydroxypropylcellulose (L-HPC) and sodium deoxycholate (NaDC) were evaluated as carriers. BZN solid dispersions containing different ratios of carrier were prepared by a freeze-drying process and characterized by SEM, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution studies. The reduced BNZ crystallinity in the new formulations was confirmed by XRD, and supported by DSC. BNZ:L-HPC solid dispersion at a 1:3 ratio (w/w) (SD-1:3 L-HPC) improved the BNZ dissolution rate (85% at 5 min) in comparison with BNZ raw material (23% at 5 min). However, NaDC formulations showed a prolonged release (24% at 30 min for SD-1:3 NaDC), due to the formation of a sustained release matrix in acidic medium. In vivo studies performed in a murine model of Chagas disease showed that the formulation achieving the highest parasitemia suppression at a low dose of 25mg/kg/day after five days of treatment was SD-1:3 L-HPC (60% of parasitemia suppression versus 33% of suppression exerted by BNZ), suggesting that BNZ:L-HPC systems enhance the bioavailability of the drug.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Palmeiro-Roldán
authors.affiliation: CEI Campus Moncloa, UCM-UPM & CSIC, Madrid, Spain; Department of Parasitology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fonseca-Berzal
authors.affiliation: CEI Campus Moncloa, UCM-UPM & CSIC, Madrid, Spain; Department of Parasitology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Gómez-Barrio
authors.affiliation: CEI Campus Moncloa, UCM-UPM & CSIC, Madrid, Spain; Instituto de Química Médica (IQM), Consejo Superior de Investigaciones Científicas (CSIC), c/Juan de la Cierva 3, Madrid 28006, Spain.
authors.forename: Vicente J
authors.initials: VJ
authors.lastname: Arán
authors.affiliation: CEI Campus Moncloa, UCM-UPM & CSIC, Madrid, Spain; Department of Parasitology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Escario
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Torrado-Durán
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain. Electronic address: torrado2@ucm.es.
authors.forename: Santiago
authors.initials: S
authors.lastname: Torrado-Santiago
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003840:Deoxycholic Acid / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000737:chemistry; D018512:Parasitemia / Q000188:drug therapy* / Q000469:parasitology; D033362:Powder Diffraction; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D003840:Deoxycholic Acid; D002482:Cellulose; C008079:hydroxypropylcellulose; C009999:benzonidazole
keywords: Benznidazole; Dissolution study; Physicochemical characterization; Solid dispersions; Trypanocidal activity