title: Albendazole Microcrystal Formulations Based on Chitosan and Cellulose Derivatives: Physicochemical Characterization and In Vitro Parasiticidal Activity in Trichinella spiralis Adult Worms.
abstract: The oral route has notable advantages to administering dosage forms. One of the most important questions to solve is the poor solubility of most drugs which produces low bioavailability and delivery problems, a major challenge for the pharmaceutical industry. Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its extended spectrum activity and low cost. Nevertheless, the main disadvantage is the poor bioavailability due to its very low solubility in water. The main objective of this study was to prepare microcrystal formulations by the bottom-up technology to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. Thus, 20 novel microstructures based on chitosan, cellulose derivatives, and poloxamer as a surfactant were produced and characterized by their physicochemical properties and in vitro biological activity. To determine the significance of type and concentration of polymer, and presence or absence of surfactant in the crystals, the variables area under the curve, albendazole microcrystal solubility, and drug released (%) at 30 min were analyzed with a three-way ANOVA. This analysis indicated that the microcrystals made with hydroxyethylcellulose or chitosan appear to be the best options to optimize oral absorption of the active pharmaceutical ingredient. The in vitro evaluation of anthelmintic activity on adult forms of Trichinella spiralis identified system S10A as the most effective, of choice for testing therapeutic efficacy in vivo.
authors.affiliation: IQUIR-CONICET, Suipacha 570, 2000, Rosario, Argentina.
authors.forename: Josefina
authors.initials: J
authors.lastname: Priotti
authors.affiliation: Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, S2000KTR, Rosario, Argentina.
authors.forename: Ana V
authors.initials: AV
authors.lastname: Codina
authors.affiliation: IQUIR-CONICET, Suipacha 570, 2000, Rosario, Argentina.|Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 570, 2000, Rosario, Argentina.
authors.forename: Darío
authors.initials: D
authors.lastname: Leonardi
authors.affiliation: Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, S2000KTR, Rosario, Argentina.|Área Parasitología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 570, 2000, Rosario, Argentina.
authors.forename: María D
authors.initials: MD
authors.lastname: Vasconi
authors.affiliation: Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, S2000KTR, Rosario, Argentina. lhinrich@unr.edu.ar.|CIC-UNR, Universidad Nacional de Rosario, Maipú 1065, 2000, Rosario, Argentina. lhinrich@unr.edu.ar.
authors.forename: Lucila I
authors.initials: LI
authors.lastname: Hinrichsen
authors.affiliation: IQUIR-CONICET, Suipacha 570, 2000, Rosario, Argentina. mlamas@fbioyf.unr.edu.ar.|Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 570, 2000, Rosario, Argentina. mlamas@fbioyf.unr.edu.ar.|Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina. mlamas@fbioyf.unr.edu.ar.
authors.forename: María C
authors.initials: MC
authors.lastname: Lamas
mesh_terms: D000284:Administration, Oral; D015766:Albendazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000493:pharmacokinetics; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D012995:Solubility; D017160:Trichinella spiralis / Q000187:drug effects*; D014235:Trichinellosis / Q000188:drug therapy*
chemical_list: D000871:Anthelmintics; D001672:Biocompatible Materials; D002482:Cellulose; C002283:hydroxyethylcellulose; D048271:Chitosan; D015766:Albendazole
keywords: albendazole; bottom-up microcrystal; chitosan; in vitro antiparasitic assay